Terpenoids and Steroids

Terpenoids and Steroids
Volume 12
A Specialist Periodical Report

~~

Volume 12
A Review of the Literature Published between
September 1980 and August 1981
Senior Reporter
J R. Hanson ScboolofMolecular Sciences, University of Sussex

Reporters
D. V. Banthorpe University College, London
R. B. Boar Chelsea College, London
S. A. Branch University College, London
G. Britton University of Liverpool
D. N. Kirk Westfield College, London
B. A. Marples University of Technology, Loughborough
J. S. Roberts University of Stirling
The Royal Society of Chemistry

Burlington House, London W1V OBN
ISBN 0-85186356-6
ISSN 0300-5992
Copyright 0 1983
The Royal Society of Chemistry
All Rights Reserved
No part of this book may be reproduced or transmitted
in any form or by any means-graphic, electronic,
including photocopying, recording, taping or
information storage and retrieval systems-without
written permission from The Royal Society of Chemistry
Typeset by Bath Typesetting Ltd., Bath and printed by

Adlard and Son Ltd., Bartholomew Press, Dorking
Made in Great Britain
Introduction
This is the last of the Terpenoids and Steroids Specialist Periodical
Reports. This title along with Aliphatic and Related Natural Product
Chemistry, The Alkaloids and Biosynthesis, has been subsumed into a
review journal entitled Natural Product Reports. Whilst maintaining the
thoroughness of coverage which has characterized the individual reports,
the new journal will aim to avoid overlap and, because it will appear more
frequently, the time delay between the completion of a chapter and publication which arises in the present reports from the irregular completion of
manuscripts. The title of the new journal allows for a greater flexibility in
scope and it will contain reports, particularly on techniques, which cut
across the traditional boundaries between the individual groups of natural
product. I should like to thank all those contributors who have made the
present series a success and I wish the chairman of the Editorial Board,
Professor Pattenden, good luck in this new venture.
J. R. HANSON
Contents
Part / Terpenoids
Chapter 1 Monoterpenoids
By D. V. Banthorpe and S. A. Branch

1 Introduction
2 Physical Methods: Chirality

Spectral and Other Physical Data
Chirality
4
4
7
3 General Synthetic Methods
8
14
14
15
19
4 The Acyclic Class

Occurrence
Synthesis of the C,, Skeleton
Reactions of 3,7-Dimethyloctadienesand their Derivatives
Reactions with Metal Complexes
Oxidation and Reduction
Cyclizations, Isomerizations, etc.
23
25
5 Tetramethylcyclohexanesand Related Compounds
29
6 The Menthane Class

General
Formation of the Menthane Skeleton
Oxidation, Reduction, and Related Reactions
Alkylation, Homologation, and Related Processes
General Reactions
32
32
33
35
39
7 The Camphane Class

Occurrence; Synthesis of the Skeleton
Oxidation-Reduction
General Reactions
44
44
45
45
8 The Isocamphane Class
47
9 The Pinane Class

Occurrence
Rearrangement, Oxidation, Reduction, Simple Functionalizations
Ring-opening
Homologation, More Complicated Functionalization
Norpinane Derivatives
48
48
48
50
51
52
vii
22
41
viii
10 The Fenchane Class
53
11 The Thujane Class

Occurrence
Reactions
53
12 The Carane Class
Reactions Preserving the Carane Skeleton

Formation of Bicycle[ 3.1 .O]hexane Derivatives
Formation of Menthane or Cyclopropane Derivatives
53
54
55
55
56
56
13 The Cyclopentane (Iridane) Class

Occurrence
Synthesis and Reactions
57
57
60
14 The Irregular Classes
61
62
62
Occurrence
Syntheses and Reactions
15 Cannabinoids and Other Phenolic Monoterpenoids
Cannabinoids
Thymol Derivatives
Occurrence
Reactions
16 Biogenesis, Chemotaxonomy, Biological Applications
Labelling Patterns; Cell-free Extracts
Tissue Cultures, Microbial Transformations
Chemotaxonomy
Metabolism, Biological Activity, Miscellaneous
Chapter 2 Sesquiterpenoids
65
65
66
66
67
67
68
72
73
73
75
By J. S. Roberts
1 Farnesane
75
2 Mono- and Bi-cyclofarnesane
78
3 Bisabolane
88
4 Sesquicamphane, Sesquipinane
89
5 Cuparane, Herbertane, L a m e , Trichothecane
92
6 Chamigrane, Widdrane
99
7 Acorane, Carotane, Cedrane, Zizaane
100
8 Cadinane, Cubebane, Oplopanane, Picrotoxane, Sativane,

Copacamphane
106
9 Himachalane, Longifolane, Longipinane
114
10 Caryophyllane, Humulane, and Related Sesquiterpenoids
115
11 Germacrane
140
ix
Contents
12 Elemane
155
13 Eudesmane
156
14 Vetispirane and Related Sesquiterpenoids
163
15 Eremophilane, Ishwarane
169
16 Guaiane, Pseudoguaiane, Patchoulane, Seychellane
172
17 Aromadendrane, Nardosinane, Neolemnane, Bicyclogermacrane
181
18 Pinguisane
183
19 Miscellaneous
184
Chapter 3 Diterpenoids
186
By J. R. Hanson
1 Introduction
186
2 Acyclic and Related Diterpenoids
186
3 Bicyclic Diterpenoids
Labdanes
Clerodanes
187
187
189
4 Tricyclic Diterpenoids
Naturally Occurring Substances
Chemistry of the Tricyclic Diterpenoids
192
192
193
5 Tetracyclic Diterpenoids
Kaurenoid Diterpenoids
Gibberellins
Grayanotoxins
At iserenes
195
195
197
199
199
6 Macrocyclic Diterpenoids
199
7 Miscellaneous Diterpenoids
201
8 Diterpenoid Total Synthesis
203
Chapter 4 Triterpenoids
207
By R. 8.Boar
1 Introduction
207
2 Squalene Group and Triterpenoid Biosynthesis
207
3 Fusidane-Lanostane Group
210
Terpemids and Steroids
4 Dammaran+Euphane Group
Tetranortriterpenoids
Pentanortriterpenoids
Quassinoids
21 5
21 7
222
222
5 Lupane Group
225
6 Oleanane Group
226
7 UrsaneGroup
230
8 Hopane Group
23 1
9 Miscellaneous
232
10 Triterpenoid Saponins
Chapter 5 Carotenoids and Polyterpenoids

By
234
235
G.Britton
1 Carotenoids
Introduction
Reviews
New Structures and Stereochemistry
Carotenoids
New Natural Products, Related to Carotenoids
Carotenoid-Protein Complexes
Synthesis and Reactions
Carotenoids
Retinoids
Carotenoid-like Compounds
Physical Methods
Separation and Assay
N.M .R. Spectroscopy
Circular Dichroism
Raman and Infrared Spectroscopy
Electronic Absorption Spectroscopy
Photoacoustic Spectroscopy
Miscellaneous Physical Chemistry
Photoreceptor Pigments
Biosynthesis and Metabolism
Biosynthesis
Metabolism
235
235
235
236
236
238
238
239
239
246
25 1
255
255
256
256
257
258
259
259
259
259
260
262
2 Polyterpenoids and Quinones

Polyterpenoids
Isoprenylated Quinones
Chemistry
Physical Methods
Biosynthesis
264
264
265
265
266
266
xi
Contents
Part I! Steroids
Chapter 1 Physical Methods
269
By D. N. Kirk
1 Structure and Conformation
269
2 N.M.R. Spectroscopy
lH Spectra
13CSpectra
lSFand 2HSpectra
273
273
274
277
3 Chiroptical Phenomena
277
4 Infrared Spectroscopy
278
5 Mass Spectrometry and Gas Chromatography-Mass

Spectrometry
Chemical Ionization Mass Spectrometry
Gas Chromatography-Mass Spectrometry
278
280
280
6 High-performance Liquid Chromatography and Other

Chromatographic Methods
281
7 Immunoassays
283
8 Miscellaneous
285
Chapter 2 Steroid Reactions and Partial Syntheses
288
By 6. A. Marples
Section A: Steroid Reactions
1 General
288
2 Alcohols and Carboxylic Acids and their Derivatives, Halides, and

Epoxides
Solvolysis, Substitution, Elimination, and Reduction
Epoxide Ring Opening
Ester, Carboxylic Acids, and Ethers
288
288
290
29 1
3 Unsaturated Compounds
Electrophilic Addition
Other Addition Reactions
Other Reactions of Unsaturated Steroids
Aromatic Compounds
292
292
294
294
295
4 Carbonyl Compounds
Reduction
0t her Reactions
Reactions Involving Enols or Enolic Derivatives
Oximes
296
296
297
299
300
xii
5 Compounds of Nitrogen, Selenium, Sulphur, and Tellurium
300
6 Molecular Rearrangements
303
7 Functionalization of Non-activated Positions
308
8 Photochemical Reactions
309
Section B: Partial Syntheses

9 Cholestane Derivatives and Analogues
31 1
10 Vitamin D, Its Metabolites, and Related Compounds
318
11 Pregnaiies
321
12 Androstanes and Oestranes
324
13 Cardenolides
325
14 Heterocyclic Steroids
327
15 Microbiological Reactions
328
Author Index
330
Part I
TERPENOIDS
1
Monoterpenoids
BY D. V. BANTHORPE AND S. A. BRANCH
1 Introduction
Owing to a chain of misfortunes, this subject has not been reviewed since Volume 9.
Consequently the present survey has to cover the literature from autumn 1978 to
that dated 3 1.12.81 (as recorded in Chemical Abstracts and Current Contents up to
1.6.82). Dr A. F. Thomas of Firmenich SA, Geneva, kindly gave access to his card
index covering the period and we are extremely grateful to him: we also thank
the Royal Society of Chemistry for providing selected abstracts.
The present half-litre pot has to contain the distillate of some 6000 monoterpenoidrelated papers: although most are trivial for the present, or indeed any, purpose,
there has obviously had to be a change of presentation from that usual in these
Reports. We have had to abandon all pretence of comprehensive coverage, and in
particular have had to be highly selective in the following categories: (a) the vast
patent literature which, although no doubt of industrial importance, often seems to
cynical eyes to be vague, trivial, and repetitive; (b) the seemingly endless reports on
occurrence and distribution of monoterpenes in plants; (c) studies on analogues of
monoterpenes (e.g. homologues of pyrethrinoids and cannabinoids) ; and ( d )
reports in journals unavailable in the U.K., and inadequately abstracted. Iridoids
are discussed but terpene alkaloids are excluded.
Even with the above restrictions, rigorous selection had to be made on the
remaining bulk of the literature. Lack of space has precluded much criticism, crossreference, and magisterial comment that are such a feature of previous Reports.
We have made an attempt to select salient papers-often those giving leading
references to earlier work within the period-but we would urge any authors who
feel that their contributions have been ignored or maltreated to send in reprints
for transmission to future Reporters.
In the following sections, the plant species that are sources of monoterpenes are
not recorded unless of some special significance, and similarly for points of stereochemistry, absolute configuration, reagents, and reaction conditions.
Excellent reviews have appeared on the synthesis of monoterpenoids,l of
cannabinoids,2 and of the use of isoprene in terpenoid ~ynthesis,~
and also on
terpenoids from marine sponge^,^ the base-catalysed isomerization of mono-
*
*
A. F. Thomas and Y. Bessiere, in TheTotal Synthesis of Natural Products, ed. J. W. ApSimon.

Wiley, New York, 1981, vol. 4, p. 451.
R. K. Razdan, in ref. 1. p. 185.
G. Cainelli and G. Cardillo, Acc. Chem. Res., 1981, 14, 89.
L. Minale, Marine Natural Products: Chem. Biof.Project., 1, 175.
t e r p e n e ~ ,and
~ iridoids.6-s Books on secondary metabolism in plants contain
chapters on mon~terpenes,~-ll
and detailed but overlapping reviews deal with the
biosynthesis of mono and other terpenoid~?~-l~
and others cover the stereochemistry of chain-lengthening and c y c l i z a t i ~ n , ~
the
~ Jimportance
~
of membrane
systems in monoterpene biosynthesis,20the metabolism of monoterpene epoxides,21
the production of monoterpenes (inter a h ) in tissue culture,22chemotaxonomy,23
and the functions of terpenoids in plants.24
2 Physical Measurements: Chirality
Spectral and Other Physical Data.-13C N.m.r. studies on hydroxy- and chloromenthanes have revealed that certain shifts are very sensitive and reliable probes
(1)
(2)
for ring onf formation,^^ and similar studies are available of menthyl enol ethers26
and of 13C--13Ccoupling in limonene and ca~vone.~
A detailed analysis of relaxation
times has been made from the 13Cspectrum for solid camphor,28and such spectra of
J. Verghese, Perfum. Flavours, 1981, 6, 23.
H. Inouye, Planta Medica, 1978, 33, 193.
L. J. El-Naggar and J. L. Beal, J. Nut. Prod., 1980, 43, 649.
* 0. P. Verma, S. Kumar, and B. C. Joshi, Herba Pol., 1980, 26, 133.
T. Robinson, Organic Constituents of Higher Plants, Corduis Press, Amherst, Mass., 4th
Edn., 1980, 352 pp.
l o R. B. Herbert, Biosynthesis of Secondary Metabolites, Chapman and Hall, London, 1981,
250 pp.
l1 M. Vickery and B. Vickery, Secondary Plant Metabolism, University Park Press, Baltimore
Md., 1981, 335 pp.
l2 H. R. Schuelte, Prog. Bot., 1976, 38, 129.
S.Nozoe and A. Kawaguchi, Methods Chim., 1978,11,223.
l4 B . V. Charlwood and D. V. Banthorpe, Prog. Phytochem., 1978, 5,65.
l6 R. Croteau, Soap, Perfum. Cosmet., 1980, 53,428.
l6 R. Croteau in Flavor and Fragrance Substances, ed. R. Croteau, D. and P. S. Verlag,
Pattensen (W. Germany), 1980, p. 13.
l7 W. D. Loomis and R. Croteau in The Biochemistry of Plants, ed. P. K. Stumpf, Academic
Press, New York, 1980, vol. 4, p. 363
l 8 0.
Cori (and nine others), Mol. Biol. Biochem. Biophys., 1980, 32, 97.
l9 D. E. Cane, Tetrahedron, 1980, 36, 1109.
2 o J. P. Corde, C. Bernard-Dagan, and M. Gleizes, Dev. PZant Biol., 1980, 6, 441.
21 S. Voight and M. Luckner, Pharmazie, 1978, 33, 632.
ea D. K. Dougall, in ref. 17, 1981, vol. 7, p. 21
*3 V. H. Heywood, J. B. Harborne, and B. L. Turner, Biology and Compositae, Academic Press,
London, 1977, two vols., 1189 pp.
e4 V. Herout, 7th International Congress on Essential Oils, 1977, vol. 7, p. 75.
25 D. Dauzonne, N. Goadsdoue, and N. Platzer, Org. Magn. Reson., 1981, 17, 18.
2s M. P. Stribel, C. G. Andrien, D. Paquer, M. Vazeux, and C. C. Pham, Nouv. J. Chim., 1980,4,
101.
27 G. Lukacs and A. Neszmelyi, Tetrahedron Lett., 1981, 22, 5053.
R. Wasylishen and M. R. Graham, Mol. Cryst. Liq. Cryst., 1979, 49, 225.
li
Monoterpenoids
norpinanes and homopinanes have been fully a n a l ~ s e d'H

. ~ ~N.m.r. studies with
shift reagents have enabled the conformations of the verbenols to be elu~idated~~131
and the stereochemistry of derivatives of camphor oxime has been analysed.32
Corrected structures for the isomeric bornane-trans-2,3-diols have been proposed.33
Analysis of the n.m.r. frequencies of the methyl groups of fenchone has assisted
analysis of the structure of the sesquiterpene c e d r a n ~ n e13C
. ~ ~and lH n.m.r. spectra
of a variety of i r i d i o l ~
and
~ ~their glycosides have been i n v e ~ t i g a t e dand
~ ~ .spectra
~~
of methylcyclopentanes have been analysed for use as models in the interpretation
of those of i r i d i o l ~ . ~ ~
Routine, but useful, interpretations of the mass spectral fragmentation patterns
under electron impact have been reported for esters of the menthane and camphane
s e r i e ~ for
, ~ thioketones
~~~~
with the thujane, pinane, camphane, and fenchane
~ k e l e t afor
,~~
[2H]limonene,42for c a n n a b i n o i d ~ , and
~ ~ -for
~ ~ the volatile components
from Pinus seedlings.47
Raman optical activity of menthane derivative^^^*^^ and of pinenes, carenes, and
related compounds50has been studied. The technique has been used to investigate
the interconversion of the pseudoaxial and pseudoequatorial forms of a-phellandreiie at low temperature^.^^ Chiroptical methods have enabled the assignment of
absolute configurations and of conformations of iridoid g l y c o ~ i d e s of
, ~ ~allylic
alcohols of the menthane and pinane classes (as their p-nitrobenzoate~),~~
and of
camphor derivatives (l).54Methylpulegene (2) is anomalous in showing no absorption maximum above 210 nm (pulegene; A,,, 232 nm), but it does exhibit a c.d.
Cotton effect :55 presumably the 3-methyl substituent prevents the diene system
29
P. Brun, J. Casanova, J. Hatem, J. P. Zahrar, and B. Waegell, Org. Magn. Reson., 1979, 12,
537.
2o
3a
33
34
35
30
37
38
3g
40
41
C. Nishino and H. Takayanagi, Agric. Biol. Chem., 1979, 43, 1967.

C. Nishino and N. Takayanagi, Agric. Biol. Chem., 1979, 43, 2323.
A. K. Singh and S. M. Verma, Zndian J. Chem., Sect. B, 1981, 20, 33.
M. A. Johnson and M. P. Fleming, Can. J. Chem., 1979,57, 318.
M. Rodriguez and J. F. Bertran, Org. Magn. Reson., 1980, 13, 263.
P. W. Thies, E. Finner, and S . David, Planta Med., 1981, 41, 15.
S. Damtoft, S. R. Sensen, and B. J. Nielsen, Phytochemistry, 1981, 20, 2717.
R. K. Chaudhuri, F. U. AM-Yazar, T. Winkler, and 0. Sticher, Tetrahedron, 1980, 36,2317.
A. Bianco, C. Bonini, M. Guiso, C. Iavarone, and C. Trogolo, Tetrahedron, 1981, 37, 1773.
A. M. Bambagiotti, S. A. Coran, V. Giannellini, G. Moneti, F. F. Vincieri, A. Selva, and
P. Traldi, Biomed. Mass Spectrom., 1981, 8, 343.
A. M. Bambagiotti, S. A. Coran, and P. Traldi, Biomed. Mass. Spectrom., 1981, 8, 356.
D. Paquer, L. Morin, M. Vazeux, and C. G. Andrieu, Red. Trav. Chim. Pays-Bas, 1981,100,
52.
D. Harris, S. MacKinnon, and R. K. Boyd, Org. Mass Spectrom., 1979, 14, 265.
43 D. J. Harvey, Biomed. Mass Spectrom., 1980, 7, 28.
Is D. J. Harvey, Biomed. Mass Spectrom., 1980, 7 , 278.
47 R. Hiltunen, S. Raisanen, and M. von Schantz, Planta Med., 1980, Suppl., p. 112.
4a P. L. Polavarapu, M. Diem, and L. A. Nafie, J. Am. Chem. SOC.,1980, 102, 5449.
4 * L. D. Barron and B. P. Clark, J. Chem. SOC.,Perkin Trans. 2, 1979, 1164.
K O L. D. Barron and B. P. Clark, J . Chem. SOC.,
Perkin Trans. 2, 1979, 1171.
51 L. D. Barron and J. Vrbancich, J. Chem. SOC.,Chem. Commun., 1981, 771.
L.-F. Tietze, U. Niemeyer, P. Marx, K.-H. Glusenkamp, and L. Schwenen, Tetrahedron, 1980,
42
53
s4
36, 735.
N. Harada, J. Iwabuchi, Y. Yokota, and H. Uda, J. Am. Chem. SOC.,1981, 103, 5590.
A. Forni, I. Moretti, G. Tome, and E. Vignudelli, Tetrahedron Lett., 1979, 907.
D. A. Lightner and B. V. Crist, Tetrahedron, 1981, 37, 685.
from attaining planarity. 7 he relationship between the polarizibility ellipsoids of

the C=C and the C, ring in pinmes, the absolute configurations, and the optical
rotations has been theoretically explored.56 Detailed and impressive consistent
force-field calculations have been made on the c.d. of menthane derivative^.^'
Several important studies have appeared concerning the detailed geometry of
certain monoterpene skeletons. Almost always (one exception; cf. ref. 58) the
thujane skeleton has been previously shown to adopt a boat conformation. A
1H n.m.r study of a variety of bicyclo[3.1.O]hexanes and thujane derivatives,
allied to calculations of the effect of ring buckling, has suggested that an alkyl
substituent at the bridgehead of the [3.1.O]-bicyclo-system (as in the thujanes)
causes the boat to twist, although this can be reduced by an axial substituent at
C-4.58More refined analysis suggests that in the thujanes the C, ring is much flatter
than in less substituted bicyclo[3.1.O]hexanes: e.g. in (3), a is 10-13", rather than
2.130" in the latter. In particular, a was deduced to be -3" for (+)-thujone (4)
(cf. ref. 59); i.e. the C, ring was virtually planar! This compares with values of 25"
and 15" for a in (+)-thujone and the epimeric (-)-isothujone deduced from
microwave spectroscopy.60 It was suggested that the latter analysis was in error
as the spectra were interpreted using the parameters determined for the parent
bicyclo[3.1.O]hexaneand no allowance was made for twisting of the ring in the more
substituted derivatives. Computed dihedral angles for the C4 rings of pinanols were
in quantitative agreement with those determined by X-ray diffraction.61The preferred conformations of trans- and cis-2-pinanol are chair and boat respectively
(with reference to the C6 ring carrying one methyl substituent), and both pinocampheols that were studied also favoured the boat conformation-but these boats
were best described as 'twisted semi-boats'. Theoretical calculations on the conformations of chrysanthemyl compounds were reported,6z and both the favoured
conformations and also the configurations at C-1 and C-8 of certain iridoid
glucosides have been elucidated by use of lH or 13C n.m.r. and m . ~Details
. ~ ~ of the
stereochemistry of the adducts of Fe(CO), with a-terpinene and o-menthadienes
have appeared.64 X-Ray studies of (5)-(7) gave the expected i n f o r m a t i ~ n . ~ ~ - ~ ~
G.c.-Fourier-transform i.r. appears to be a technique of great potential for the
identification of monoterpenes in plant extracts: in some cases it is claimed to be
superior to g.c.-m.s. but generally the methods are complementary.68 Another
recent procedure is droplet counter-current chromatography which is a modification
66
67
6O
61
6z
63
64
66
68
67
S. G. Vulfson and V. F. Nikolaev, Izv. Akad. Nauk SSSR, Ser. Khim., 1981, 2259.
R. D. Singh and T. A. Keiderling, J. Am. Chem. SOC.,1981, 103, 2387.
J. C. Rees and D. Whittaker, Org. Magn. Reson., 1981, 15, 363.
(4) has traditionally been known as (+)-isothjone. We here adopt a more rational, if little used,
nomenclature; cf. S. P. Achorya et al. J . Org. Chem., 1969,34,3015.
Z. Kisiel and A. C. Legon, J . Am. Chem. SOC.,1978, 100, 8166.
J. Texter and E. S. Stevens, J. Org. Chem., 1979, 44, 3222.
G. Castellani, R. Scordamaglia, and C. Tosi, Gazz. Chim. Ztal. 1980, 110, 457.
L.-F. Tietze, U. Niemayer, P. Marx, and K.-H. Glusenkamp, Tetrahedron, 1980, 36, 1231.
A. J. Birch and 17 others, Tetrahedron Supplmt., NO. 1, 1981, 37, 289.
R. A. Pauptit and J. Troffer, Can. J . Chem., 1980, 58, 2805.
V. G. Andrianov, Yu. T. Struchkov, V. A. Blinova, and I. I. Kritskaya, Zzv. Akud. Nuuk
SSSR, Ser. Khim., 1979, 2021.
R. Rogues, J. Sotiropoulous,G. Feuillerat, G. Germain, and J. P. Declercq, J . Chern. Res. (S),
1980, 370.
J. T. McDonard and V. F. Valasinsky, Proc. SPIE, Int. SOC.Opt. Eng., 1981, 154.
Monoterpenoids
P
(3)
(4)
of counter-current distillation. This has been applied very successfully to the bulk
separation of iridoid g l ~ c o s i d e sA. ~method
~ ~ ~ ~has been claimed for the identification of terpene alcohols at the pg level:71this involved g.c.-m.s. after reduction
over platinum with lithium aluminium hydride. As a result, different substrates were
said to give a pattern of products with characteristic skeleta: thus borneol yielded
camphane or tetramethylcyclopentanes.
Photoelectron spectra of fenchone derivative^'^ and e.s.r. spectra of the paramagnetic adducts between organic Si-, Ge-, and Sn-centred radicals and camphor
and t h i ~ c a r n p h ohave
r ~ ~ been studied.'
Chirality.-The simultaneous presence of (8) and (9) (L= Yb"', GaIII, or Prrrl
splits the lH and lSC n.m.r. signals of chiral a-pinene, limonene, and camphene.
As a consequence the enantiomeric purities could be readily determined :74 previously, hydrocarbons were not amenable to such techniques. Compound (9)
augmented the Ag salt shift but did not interact alone.
Ally1 boronates of substituted camphor diols (10) added to acetaldehyde to
yield (1 l), which on base treatment cleaved to give 86 % optically pure pent-4-en-
K. Hostettmann, M. Hostettmann-Kaldas, and 0. Sticher, Helv. Chim. Acta, 1979, 62, 2079.
R. K. Chaudhuri, 0. Salama, and 0. Sticher, Planta Med., 1980, 40, 164.
71 B. A. Bierl-Leonhardt and E. D . Devilbiss, Anal. Chem., 1981, 53,936.
l e D. C. Frost, N. P. C. Westwood, and N. H. Werstiuk, Can. J. Chem., 1980,58, 1659.
73 A. Alberti, M. Guerra, and G. F. Pedulli, J. Am. Chem. Soc., 1981,103,6604.
74 W. Offermann and A. Mannschreck, Tetrahedron Lett., 1981,22,3227.
6@
70
2-01: pinane diols were less effective.75 B-3-Pinanyl-9-borabicycl0[3.3.1

Inonane
[prepared from ( +)-x-pinene] proved an exceptionally effective reagent for the
stereospecific reduction of [I -2H,]-aldehydes to [2H,]-primary alcohols : thus
[CHO-2H,]benzaldehyde was converted into optically-pure ( +)-[ 1-2H,]benzyl
A detailed mechanistic discussion of the reaction was appended. The
chiral titanium compound (1 2) converted benzaldehyde into l-phenylethanol in low
(ca. 14 %) optical yield. 7 7 Chiral amines, e.g. N-isopropyl-( -)-menthylamine, were
used as bases in asymmetric condensations between bromoacetates and ketones in
Reformatsky-type reactions, but the optical yields were generally poor, at a
maximum 400/;j.78The rhodium complex (13) was resolved: the enantiomers were
both yellow, although the racemic mixture was red-green. 7 9
3 General Synthetic Methods
Monoterpenes are widely used as substrates in the development of new synthetic

reagents and routes. However, many of these studies refer to a one-off use of a
particular compound as one of many models and such are not discussed here unless
of especial interest. We rather review the salient work involving specific functionalization and modification of the class.
,,,,*ao
Me,C=CHCH,MgBr-CuI
75
76
77
76
78
>
pcl
T. Herold, U. Schrott, R. W. Hoffmann, G . Schnelle, W. Ladner, and K. Steinbuch, Chem.

Ber., 1981, 114, 359
M. M. Midland, S. Green, A. Tramontano, and S . A . Zderic, J . Am. Chem. SOC.,1979, 101,
2352.
M. T. Recti, R. Steinbach, B. Wenderoth, and J. Westermann, Chem. fnd. (London), 1981, 541.
S. Brandange, S . Josephson, L. Morch, and S . Vallen, Acta Chem. Scand., Ser. B, 1981,35,273.
V . Schurig, Angew. Chem. Int. Ed. Eng., 1981, 20, 807.
Mono terpenoids
The ene reaction of aldehydes with alkenes provides a potentially valuable route
to homoallylic alcohols [cf. (14a) + (14b)l. Coupling of isoprene with 3-methylbutan-1-a1 yielded ( 1 5) in excellent yield, and limonene similarly, reacted (at the
Cii
lii
6
H COMe
3
OH
Reagents: i, AgSbF6; ii, H,O; iii, MeMgI; iv, MeOH
Scheme 1
exocyclic double bond) to yield a hydroxybisabolane. 8o Dimethylaluminium

chloride (a mild Lewis acid and also a proton scavenger) catalysed the process and
proton-initiated reactions did not occur. A novel synthetic method has been
developed for the synthesis of optically active terpenes by the ring-opening of
(R)-( +)-p-methyl-propiolactone :81 the sequence to citronellic acid (1 6) and
pulegone (17) utilized the previously developed step whereby a regiospecific
attack of a Grignard reagent on the substrate was catalysed by cuprous iodide.
An elegant new route to monoterpenes could possibly be developed to give specific
labelling with tracer: the key intermediate was an oxonium salt (18), and pathways to cis-terpin (19), 1,8-cineole (20), and a-terpineol (21) are shown in Scheme
1.B2 An effective method of converting camphor into epicamphor and menthone
into carvomenthone involved the route (22)-+(23).83 A very detailed study has
been made of the linkage of C, units, via the elaboration of a C,,-cyclopropyl
8o
BB
88
B. B. Snider and D. J. Rodini, Tetrahedron Lett., 1980, 21, 1815.

T. Sato, T. Kavara, A. Nishizawa, and T. Fujisawa, Tetrahedron Lett., 1980, 21, 3377.
J. P. Begue, M. Charpentier-Morize, D. Bonnet-Delpon, and J. Sansoulet,J . Org. Chem., 1980,
45, 3357.
T. Nakai and T. Mimura, Tetrahedron Lett. 1979, 531.
10
intermediate (24) formed from reaction of C,-carbenes and a C,-alkene. Typically,

acid treatment of (24) led to a product showing head-to-tail linkage of the units
(25), whereas base treatment followed by acidification gave irregular structures
(26) (Scheme 2):84 treatment of (24) and its analogues with dissolving metals
or peracids also led to novel, functionalized but regular structure^.^^ Methods
for the formation of allylsilanes from geraniol, linalool, and myrtenola6 and
A
-
- Li
NNHTs
NNTs
BuLi,
MeSSMe
Li
NNTs
(23)
from verbenola7 have been reported. The gem-di-(trimethylsilane) derived from
geraniol reacts with acid to yield citronellene (3,7-dimethylocta- 1,6-diene)87.
A general route has been developed to a,p-unsaturated aldehydes of homomonoterpenes,8s and various monoterpene y- and 8-lactones have been synthesized by the
Wittig-Horner reaction. 8 9 Geraniol and also pinane derivatives have been elaborated into a-substituted methylacrylates via a Claisen-o-ester rearrangement with
trimethyl p-methoxyorthopropionate using trimethylbenzoic acid as catalyst,g0
liii
OMe
Reagents : i, BF, etherate-MeOH; ii, KOBut-DMSO ; iii, H+-MeOH
Scheme 2
E4
B6
B6
87
L. Crombie, P. J. Maddocks, and G. Pattenden, Tetrahedron Lett. 1978, 3479.

L. Crombie, P. J. Maddocks, and G. Pattenden, Tetrahedron Lett. 1978, 3483.
C. Biran, J. Dunogues, R. Callas, J. Gerval, and T. Tskhovrebachvili, Synthesis, 1981, 220.
D . Pandy-Szekeres, G. Deleris, J. P. Picard, J.-P. Pillot, and R. Callas, Tetrahedron Lett., 1980,
21, 4267.
T. Hiyama, A. Kanakura, H. Yamato, and H. Nozari, TetrahedronLett. 1978,3051.
H. Biedrzycki, K. Witkiewks, and Z. Chabudzinski, Pol. J . Chern., 1980, 54, 45.
S. Raucher, J. E. Macdonald, and R. F. Lawrence, Tetrahedron Lett., 1980, 21,4335.
Monoterpenoids
11
e.g. (27) -+ (28), and the epoxides of pulegone and piperitone have been prepared
by the Wittig reaction.g1 Treatment of ally1 acetates of the menthane and pinane
classes (e.g. those of carveols and myrtenol) with sodium diethylmalonate in the
presence of diphenylphosphinoethane and a Pd catalyst effected the transformation
(29) -+ (30), with obvious scope for further modification. 92 Another reaction leading
to valuable synthetic intermediates is the addition of dichlorocarbene to camphene
followed by reduction to yield (31) and (32);93 P-pinene and limonene behaved
similarly.
LoH
*
MeO(CH,),C(OMe),catalyst
(28)
&Ac
4rb
+O2EO,
R
(30)
(29)
(31)
(32)
The reactions of metal complexes of monoterpenes continue to be actively

explored and many specific examples will be found in later sections. Of general
interest are the dimerization of x-allyl-Pd complexes of or- and P-pinenes and of
carvone that are effected by irradiation at 366 nmg4and the thermal decompositions
of (x-ally1)nickel halide complexes of, e.g., isoprene (33), to form m ~ r c e n e . ~ ~
Hydrosilylation of I ,3-dienes (e.g. isoprene, myrcene, ocimene) was found to be a
regiospecific 1,6addition for Pd complexes but followed the alternative route for
Rh compounds; a good discussion is appended.96 A series of dimers of isoprene
vTNiBrl2
(33)
-OH
--+
&OH
(34)
v
OH
-&OH
(35)
O3
9'
OS
N. Bensel, J. Hohn, H. Marschall, and P. Weyerstahl, Chem. Ber., 1979, 112, 2256.
J. C. Fiand and J. L. Malleron, Tetrahedron Lett., 1980, 21,4437.
S. Watanabe, T. Fujita, K. Suga, and K. Kasahara, Aust. J . Chem., 1981, 34, 1161.
J. Muzart and J. P. Pete, J . Chem. SOC.,Chem. Commun., 1980, 256
L. S. Hegedus and S. Varaprath, Organometallics, 1982, 1, 259.
I. Ojima and M. Kumagi, J . Organomet. Chem., 1978, 157, 359.
12
bonded at 1-2, 1-3, 1-4, 2-4, 3-4, and 4-4 positions were prepared by suitable
regiocontrolled catalysis by transition metals of the coupling of 2-methylbut-2ene- 1,6diylmagnesium or 3-methylbut-2-enylmagnesium chloride with C,-alkenyl
halides.97 Various terpene amines have been obtained in excellent yields by Pdcatalysed telomerization of isoprene with NH,. 98
Conditions have been worked out for the conversion of allylic alcohols into
1,3-dienes (e.g. nerol-tmyrcene, geraniol+trans+P-ocimene)
by a sequence
involving epoxidation, trimethylsilylation, ring-opening, desilylation, formation
of diol, then of dibromides, and debromination, e.g. (34) --f (35).99 Reaction of a
variety of monoterpenes with HOCl-CH,Cl, resulted in addition of chlorine
followed by shift of the double bond: dechlorination (Zn) led to a-olefins (60-80 %),
and the chloro-derivative of citronellol could be efficiently converted into rose
oxide [2-(2-methylprop-1-enyl)-4-methyltetrahydropyran] by successive treatment
with acid and base.loO Dehydrations of allylic monoterpenols with carbodiimideslOlaand anhydrous C U S O , were
~ ~ ~effective.
~
Hydroalumination of p-pinene,
camphene, and a-thujene in the presence of 0, gave after work-up the product of
anti-Markovnikov addition (73 % trans-product, 85 % endo, and non-stereoselective,
respectively).102 In contrast, hydroboronation (TiC1,-NaBH,) gave 85 % cisproduct from p-pinene and mainly isopinocampheol from ~ c - p i n e n e . ~ ~ ~
A very useful functionalization of the isopropylidene terminus of isoprenoids led
to the formation of terminal trans-allylic alcohols (36) * (37), e.g. 10-hydroxy-
geraniol. Step (i) was highly regioselective and (ii) could be very effectively carried
out by the Evans procedure.lo4Preoccupations with the reactions of monoterpenes
(thujenes, menthenes, and carenes) and other 1-methylcyclohexenes has obscured
the fact that 1-methylcycloalkenes with four-, five-, seven-, eight-, or twelve-membered rings show predominantly syn-side addition in the ene oxidation with photochemically generated singlet oxygen (38 ; route i). 1-Methylcyclohexenes, however,
show anti-side addition (route ii): the theoretical reasons for this dichotomy have
been very convincingly
The PdCl, complex from carvone was conY. Kajihara, K. Ishikawa, H . Yasuda, and A. Namarnura, Bull. Chem. SOC.J . , 1980, 53,3035.
W. Keim and M. Roper, J . Org. Chem., 1981, 46, 3702.
Bs A. Yasuda, S. Tanaka, H. Yamamoto, and N. Nozaki, Bull. Chem. SOC.J., 1979, 52, 1752.
looS. G. Hegde and M. K. Vogel, Tetrahedron Left., 1980, 21, 441.
lo1 A. Trius, A. Trivino, and A. Virgili, Anales de Quim., 1980, 76, 58.
l 0 l b R. V. Hoffmann, R. D. Bishop, F. M. Fitch, and R. Harderstein, J . Org. Chem., 1980, 45,
917.
l o 2 A. V. Kuchin, L. I. Alkmetor, V. P. Yurev, and G . A. Tolstikov, Zh. Obshch. Khim., 1979, 49,
1567.
l o 3 S. Kano, Y. Tanaka, and S. Hibino, J . Chem. SOC.,Chem. Commun., 1980, 414.
lo*Y. Masaki, K . Hashimoto, and K. Kaji, Tetrahedron Lett., 1978, 4539.
K. H. Schulte-Elte and V. Rautenstrauch, J. Am. Chem. SOC.,1980, 102, 1738,
97
88
Monoterpenoids
13
verted by irradiation in the presence of 0, into (39)lo6whereas treatment of carveol

or myrtenol with Pd in the presence of PPh, and a base yielded the ketone.lo7
Geraniol and carveol were oxidized at the alcohol group by 0, in the presence of
[ R U C ~ , ( P P ~ ~ and
) J , ~menthol
~~
was converted into menthone by
Methods have been developed for the epoxidation of a variety of types of monoterpenes with t-butyl hydroperoxides over metal catalysts.l1
a,@-Unsaturatedketones (e.g. pulegone) were specifically reduced at the 1,2positions by Lu"l-NaBH,"l

and the conjugated double bond of citral was
selectively attacked by (MeO),SiH in the presence of [ R U C ~ ~ ( P P ~Pulegone
,)~].~~~
and its analogues were readily reduced with $-branched trialkylaluminium compounds: the yield and stereoselectivity were highly dependent on the solvent, and
asymmetric induction could occur when chiral reducing agents were used.l13 Chiral
menthyl or neomenthyl groups were ligated to Rh-phosphine complexes to form
soluble catalysts for enantioselective hydrogenation of geranic acid.l14J16Catalytic
reductions of a-pinene, limonene, and others have been studied.l16J1' Ca(NH,),Me,CHOH-Me,CHCH,OH
was claimed to be more effective than a Birch
reagent for the reduction of phenol ethers (e.g. methyl thymyl ether) to a,@unsaturated ketones.l18 Such ketones (carvone, pulegone) were rapidly reduced (to
saturated ketones after work-up) by the liquid reagent 'lithium bronze', Li(4NH3);
this was more convenient than the traditional use of blue solutions of Li in NH,.l19
J. Muzart, P. Pale, and J. P. Pete, J . Chem. SOC.,Chem. Commun., 1981, 668.
lo6
Y.Tamaru, K, Inoue, Y. Yamada, and Z. Yoshida, TetrahedronLett., 1981,22,1801.
lo7
M. Matsumato and S. Ito, J. Chem. SOC.,Chem. Commun., 1981, 907

Y. Masuyama, A. Tsuhako, and Y. Kurusu, Tetrahedron Lett., 1981, 22, 3973.
D. V. Banthorpe and S. E. Barrow, Chem Znd. (London), 1981, 502.
111 A. L. Gemal and J. L. Luche, J. Am. Chem. SOC.,1981, 103,5454.
M. Matsumoto, Y . Hoshino, and Y. Nagai, Bull. Chem. SOC.J., 1981, 54, 1279
113 G. Giacomelli, A. M. Caporusso and L. Lardicci, Tetrahedron Lett., 1981, 22, 3663,
114 D.Valentine, K.K. Johnson, W. Priester, R. C. Sun, K . Toth, and G. Saucy, J . Org. Chem.,
lo8
log
1980,45,3698.
115
116
117
11*
D.Valentine, R.C. Sun, and K. Toth, J . Org. Chem., 1980, 45, 3703.
A. Fischli and P. M. Muller, Helv. Chim. Acta, 1980, 63, 1619.
A. Fischli and P. M. Muller, Hefv. Chim. Acta, 1980, 63, 4529.
V. V. Bazylchik, T. N. Overchuk, and P. I. Fedorov, Zh. Org. Khim., 1978, 14, 2085.
R. H. Mueller and J. G . Gillick, J . Org. Chem., 1978, 43, 4647.
14
It was recommended that alkali-metal-NH, reduction of ketones should be

conducted in the presence of NH,+: this follows from the finding that reduction of
[3,3-2H2]camphorand quenching in the absence of the ion gave epimeric alcohols
with one or two atoms of tracer and complex products formed by disproportionation, abstraction of H from the medium, and pinacolic coupling. In the presence of
NH,Cl, exclusively [3,3-2H2]-alcohols were formed with Li, Na, or K. It was
concluded that a mechanism proposed by House (1972) predominated when NH4+
was the proton source.12o
Novel regioselective electrochemical ene-type chlorinations (40) -+(41) to yield

ally1 chlorides have been developed although the product selectivity was highly
dependent on the choice of halide ion and the solvent: e.g. allylic chlorides,
chlorohydrins, dichlorides, or epoxides may be formed.121Electrochemical oxyselenation-deselenation (involving addition of PhSeOH) in the presence of ROH
(R = alkyl) also led to allylic-type addition of OR with shift of the double
The synthesis of chiral monoterpenesulphonic acids for use in the resolution of
amino-acids has been
as has the enzymic resolution of chiral acyclic
monoterpenols via the asymmetric hydrolysis of the corresponding acetates by
rnicro-organism~.~~~
Lipases from micro-organisms catalysed the formation of
esters from geraniol and lower fatty acids in up to 50% yields.lZ5Other interesting
papers dealt with methods for acylation126and carbonylation,lZ7isomerization of
monoterpene hydrocarbons on heating in dipolar aprotic solvents,12*and the
dehydrogenation of terpenoids on c h r o r n ~ p l a t e s . ~ ~ ~
4 The Acyclic Class
Occurrence.-In this, and later sections, only novel (or so-claimed !) compounds
or known compounds in unexpected environments will be considered. A variety of
mono- and di-hydroxy-linalools [e.g. (42), (43)] substituted at C-6 and C-7 have
been found in grapes 130-132 and may be the precursors of more volatile usual
V. Rautenstrauch, B. Willhalm, W. Thommen, and U. Burger, Helv. Chim. Acta, 1981, 64,
2109.
lz1 S. Torii, K. Uneyama, T. Nakai and T. Yasuda, Tetrahedron Lett., 1981, 22, 2291.
S. Torii, K. Uneyama, M. Ono, and T. Banou, J . Am. Chem. SOC.,1981,103,4606.
I z 3 S. C. Traynor and B. J . Kane, J . Org. Chem., 1979,44, 1557.
12* T. Oritani and M. Yamashita, Agric. Biol. Chem., 1980, 44, 2407.
l Z 5 M. Iwai, S. Okumura, and Y . Tsujisaka, Agric. Biol. Chem. 1980, 44, 2731.
128 R. Couffignal and J. L. Moreau, Tetrahedron Lett., 1978, 3713.
12' S. D. Pirozhkov, N. V. Puzitski, T. N. Myshewnova, N . G. Ryabova, and S. S. Poddubnaya,
Izv. Akad. Nauk SSSR, Ser. Khim., 1979, 784.
128 A. Matawowski, Polish J . Chem., 1980, 54,469.
129 J. C. Kholi, R. Gupta, A. K. Arora, and K. Ushminder, J . Chromatogr., 1981, 210, 370.
I 3 O P. J . Williams, C. R. Straws, and B. Wilson, Phytochemistry, 1980, 19, 1137.
H. Etoh, K. Ina, and M. Iguchi, Agric. Biol. Chem., 1980, 44, 2999.
138 A. Rapp, W. Knipser, and L. Engel, Vitis, 1980, 19, 226 (Chem. Abstr., 1981, 94, 82 103).
pH PH
Mono terpenoids
15
COZH
OH
(43)
(45)
m o n o t e r p e n e ~Two
. ~ ~ 5-ketolinaloyl
~
derivatives (previously ~ynthesizedl~~)
occur in
Citrus ~ p p . , 1and
~ ~ a corresponding 4-hydroxy-compound (cornusol) has been
isolated from a Curnus spp.136The acid (44)was the monoterpenoid moiety of a
~ap0nin.l~'Geranyl-p-D-glucoside was readily formed, transported, and metabolized when apples were injected with the alcohol;13s this and the linaloyl glucoside that occur in tea shoots were cleaved on mechanical disruption.139 These
results suggest that glycosides may generally be storage and/or transportable forms
of certain monoterpenols. 3,7-Dimethylocta-(Z)3,6-dien-1-al,1407-hydroxycitronellic
acid,141geranic
geranyl dihydroquinones and the corresponding aromatics,l43
and sulphur derivatives of m y ~ c e n e[e.g.
l ~ ~ (45)] have been isolated from a variety of
plant species. Halogenated dimethyloctadienes, e.g. 8-bromo-3,7-dichloro-2,6dimethyl-octa-1, (E)S-diene, continue to be found in marine red algae.145-147
Synthesis of the C,, Skeleton.-Isoprene in the presence of Pdo catalysts1@or
telomerized with its
gave mainly citronellene (3,7-dimethylocta- 1,6diene) and geranyl chloride respectively, although an interesting minor product
(7 %) of the latter reaction was 2,7-dimethyl-3-chloro-octa-1,6-diene-anirregular
P. J. Williams, C. R. Strauss, and B. Wilson, J . Agric. Food Chem., 1980, 28, 766.
0. S. Park, Y.Grillasia, G. A. Garcia, and L. A. Maldonado, Synth. Cornrnun., 1977, 7 , 345.
lS6 T. Kitahara, Y. Takagi, and M. Matsui, Agric. Biol. Chem., 1980, 44, 897.
T. Kurihara and M. Kikuchi, Yukuguku Zasshi, 1978, 98, 969.
13' Y.Okada, K. Koyama, K. Takahashi, T. Okuyama, and S . Shibata, Plantu Med., 1980,40,185.
R. B. H. Wills and F. M. Scriven, Phytochemistry, 1979, 18, 785.
139 T. Takeo, Phytochemistry, 1981, 20, 2145.
140 J, M. Sandra and P. Cunat, Phytochemistry, 1980, 19, 89.
141 M. L. Sethi, S. C. Taneja, K. L. Dhar, and C. K. Atal, Indian Perfum., 1979,23,167.
A. Nahrstedt, U. Vetter, and F. J. Hammerschmidt, Planta Med., 1981, 42, 313.
143 R. J, Capon, E. L. Ghisalberti, and P. R. Jefferies, Phytochemistry. 1981, 20, 2598.
144 T. L. Peppard and J. A. Elvidge, Chem. Znd. (London), 1979, 552.
Ips R. W. Dunlop, P. T. Murphy, and R. J. Wells, Aust. J . Chem., 1979, 32, 2735.
146 D.B. Stierle, R. M. Wing, and J. J. Sims, Tetrahedron, 1979, 35, 2855.
P. Bates, R. W. Blunt, M. P. Hartshorn, A. J. Jones, M. H. G. Munro, W. T. Robinson, and
S . C. Yorke, Aust. J . Chem., 1979, 32,2545.
14* K. Nozaki, Eur. P., 19 960/1980.
149 A. Erm, M. Heinvali, T. Valimae, and K. Laats, Eesti, NSV. Tead. Akad. Toim.,
Keem., 1981,
133
134
30, 56.
16
nerol,
isogeraniol
(51)
Reagents: i, H+; ii, -CH,O;
iii, -H,O;
iv, Me,C=CHCH,CI-BuLi;
v, N a or electrochemical
Scheme 3
product of tail-to-tail linkage. Dimerization with PdO and MeC0,H led (on
work-up) to 2,6-dimethylocta-2,7-dien-1-01 (regu1ar)l5Oor, under activation by Mg
in the presence of B(OBU"),,~~~
to a mixture of regular (e.g.geraniol and oc-geraniol)
and tail-to-tail linked alcohols. With Zr complexes the products were exclusively
tail-to-tail linked trienes.15, Isoprene on treatment with Mg formed a series of
dimeric and polymeric complexes in equilibrium, which on addition of 2-chloromethylbutadiene gave myrcene and irregular hydrocarbons formed by 1-2 and 1-3
linking.153Coupling of the trimethylsilyl derivative (46) of isoprene with 3-methylbutyraldehyde gave ipsenol (47) .154 A very detailed mechanistically orientated
study of theaction of HC104, F3C0,H, and HC02H on the 1,l and 3,3-dimethylallyl
alcohols has secured conditions for 'biomimetic' condensations leading to 3,7dimethylocta-6-ene-l,3-diol(86 %; and thence to geraniol) and also to lavandulyl
compounds (irregular).155Use of other suitably functionalized isoprenes has led to
the sequences (48)+(49)156 and (50)+(5 I) (Scheme 3).157J58
Other interesting routes for the construction of an acyclic Clo skeleton from C,
precursors are the selective y-alkylation of Cu enolates derived from oc,p-unsaturTakagago Perfumery Co., Jap. P., 39 366/1980.
B. Ceskis, A. M. Moiseenkov, M. I. Struchkova, and A. V. Semenovski, Izv. Akud. Nuuk
SSSR, Ser. Khim., 1981, 365.
152 H. Yasuda, Y.
Kajihara, K . Nagasuna, K. Mashima, and A. Nakamura, Chem.Lett., 1981,719.
lS3 Y.Kajihara, K. Ishikawa, H. Yasuda, and A. Nakamura, Bull. Chem. SOC.
J., 1980, 53, 3035.
150 A. Hosomi, M. Saito, and H. Sakurai, Tetrahedron Lett., 1979, 429.
156 D. Babin, J.-D. Fourneron, and M. Julia, Bull. SOC.Chim. France, Part IZ, 1980, 588.
156 N. A. Romanov, E. A. Kantor, R. S. Musavirov, R. A. Karakhanov, and D. L. Rakhmankulov,
Zh. Org. Khim., 1981, 17, 1762.
lS7 A. M. Moiseenkov, E. V. Polunin, and A. V. Semenovsky, Tetrahedron Lett., 1979, 4759.
lS8 A. M. Moiseenkov, E. V. Polunin, and A. V. Semenovsky, Angew. Chem. Znt. Ed. Engl., 1981,
150
151
20, 1057.
Mono terpeno ids
17
Me& =CHCH,Br
c02h
(53)
A X LOSiMe,
i
P0 h
w;
OSiMe,
(54)
(55)
ated
e.g. (52)+(53) ;the use of 3-methylbuta-l,3-dienyl phenylsulphoneas a
Michael acceptor of lithiated and protected cyanohydrins, e.g. (54)455)160 (this
has led to routes to tagetones and ocimenones); and y-alkylation via metalated
unsaturated amides, e.g. (56)-+(57).l6l
+o NHMe
i: ~ ~ c = , , c ~ s ~ r
$NHMe
fHMe
(56)
(57)
An ingenious method of linking two C , units to give ultimately 10-hydroxygeraniol, a precursor for loganin and iridodial, involved photochemical coupling of
2,5-dihydro-3-methylthiophenSS-dioxide (58) with citraconic anhydride (59)
followed by thermal extrusion of SOz, Cope rearrangement of the resulting
divinyl ester, and suitable functionalization (Scheme 4).162
This work demonstrates
that (58) and its analogues offer an alternative method to the use of cyclobutenes
for the stereospecific synthesis of cis- 1,2-divinyl systems and trans,trans- 1,5-dienes.
P. M. S a w and J. A. Katzenellenbogen, J . Org. Chem., 1981,46,239.
E. Guittet and S. Julia, Synth. Cummun., 1981, 11, 709,
M. Majewski, G. B. Mpango, M. T. Thomas, A. Wu, and S. Snieckus,J . Org. Chem., 1981,46.
lSn
160
2029.
J. R. Williams and C. Liu, J . Chem. Suc., Chem. Cummun., 1981, 752.
18
K-q--;::
OH
Reagents: i, h v ; ii, CH,N,, A ; iii,A
Scheme 4
A variety of routes have been explored for linkage of (rn + n) units (m + n =
10;m,n # 5.) Methylhexenone (60) could be converted into the terminal acetylene
(61) and thence into (E)-trisubstituted olefins such as g e r a n i ~ I , ~ and
~ ~ Jcould
~ * also
be protected, oxidized at a gern-dimethyl, and functionalized to give 10-hydroxyl i n a l o 0 1 ~or~ ~converted into [1,2J4C2]geranial and thence into ionones.166Hydromagnesiation of prop-Zynylic alcohols proceeds with stereo- and regio-specificity
(64)
under mild conditions in almost quantitative yields: thus nerol has been synthesized
from (62).16' Procedures involving coupling of (C, + C,) units (Me,C=CH(CH2),C1 + MeCOCHClCH2C1) to give geranyl acetate168and of (C, + C,) units
163
E. Negishi, A. 0. King, W. L. Klina, W. Patterson, and A. Silveira, J . Org. Chem., 1980, 45,
2526.
16'
N. Okukado and E. Negishi, Tetrahedron Lett., 1978, 2357.

0. P. Vig, S . S. Bari, I. R. Trehan, and R. Vig, Indian J . Chem., Sect. B, 1979, 17, 619.
R. R. Muccino and C. A. Wasiowich, J. Labelled Comp. Radiopharm., 1980, 17,463.
F. Sato, H. Ishikawa, H. Watanabe, T. Miyanke, and M. Sato, J . Chem. SOC.,Chem. Commun.,
16@
K. K. Mathew, P. S . Raman, and T. G . B. Antbarjanam, Indian J. Chem.,Sect. B, 1981,20,340.
1*
165
1981, 718.
19
Monoterpenoids
_.,
SPh
q S i M e 3
SPh
SiMe,
SPh
J,iii
oxidation ; reduction
t
o
Reagents : i, NaH-Me,SiCH,I ; ii, Grignard ; iii, SO&l,-Et,N, HMPA-LiCl

Scheme 5
[(63)+(64)] have been worked out. Compound (63) has been proposed as a new
key intermediate for the synthesis of a variety of acyclic m o n ~ t e r p e n e s .PhS
~~~
groups are well known to migrate to an adjacent positive centre, and by incorporation of a Me,% group into the molecule it has been possible to encourage rearrangement from a secondary to a secondary or even a secondary to a tertiary
migration terminus. The method was illustrated by the efficient synthesis of geraniol/
nerol and l i n a l ~ ofrom
l ~ ~ (65)
~ as shown in Scheme 5 .
Trimethylsilyl-enol ethers of pentane-2,4-dione and methyl acetoacetate reacted
with linalool at room temperature without catalysts to yield the trimethylsilyl ether
(85 %), excellent for g.1.c. or m.s.171 Other interesting routes involving couplings of
(C, + C4) and (C, + C,) units to give myrcene have been r e p ~ r t e d ~and
~~J~~
elegantly conceived several-stage syntheses of (I?)-( -)-ipsdienol and the (S)-( +)isomer [a pheromone of Ips beetles (66)] were based on a previously developed
route to ipsenol (47) and utilized (I?)-( +)-glyceraldehyde and (R)-( +)-malic acid
respectively as starting rnate~ia1s.l'~
J?
HO
Reactions of 3,7-Dimethyloctadienes and their Derivatives.-Geraniol

and nerol
were sequentially converted into their chlorides and cyanides with no allylic
rearrangement on treatment with (Bu"),P-CCl,-KCN in the presence of crown
ether.17s 2,4,6-Trichloro-4-bromocyclohexa-2,5-dienone
selectively brominated
geraniol derivatives (functionalized at C-1) under mild conditions to give the
T. Mandai, H. Yamaguchi, K. Nishikawa, M. Kawada and J. Otera, Tetrahedron Lett., 1981,
lo@
22,763.
170
171
178
17a
17*
17ti
I. Fleming, I. Paterson, and A. Pearce, J. Chem. SOC.,Perkin Trans. I , 1981, 256.

T. Veysoglu and L. A. Mitscher, Tetrahedron Lett., 1981, 22, 1303.
H. Kleijn, H. Westmijze, J. Meijer, and P. Vermeer, Recl. Trav. Chim.Pays-Bas, 1980,99,340.
Y. Ueno, H. Sano, S. Aoki, and M. Okawara, Tetrahedron Lett., 1981, 22, 2675.
K. Mori, T. Takigawa, and T. Matsuo, Tetrahedron, 1979, 35, 933.
A. Mizuno, Y. Hamada, and T. Shioiri, Synthesis, 1980, 1007.
20
6,7-dibromo-compounds together with products substituted at C- 10 and at C-6.17s

10-Bromogeranyl methyl ether was readily isomerized to the 8-bromo-compound
and products of allylic rearrangement.l 7 7 The isomers of 2,3-epoxygeraniol yielded
1 ,2-dihydroxy-myrcene and -0cimene on treatment with Ti(OPr'), : however,
(70)
erythro-l,2-epoxylinalool(hydroxy and epoxy cis) with vanadium catalysts gave
dihydroxymenthanes whereas the threo-isomer was decomposed; Ti(OPri), catalysed the reaction of the erythro-compound but threo was recovered unchanged.
These results were rationalized by 'OH-assisted delivery' of the metal to the oxiran
ring.17s The synthetic uses of bisulphite adducts of citrals have been explored.17B
Myrcene deuteriated at (C-8 + C-10) has been prepared,lsOandthe 3-fluoromethyl-,
3-difluoromethyl-, and 3-trifluoromethyl-geraniols have been synthesized for use
as substrates of prenyltransferase.lsl The key reaction that defined the stereochemistry of the double bond was the syn-addition of a (4-methylpent-3-en- 1-yl)
copper reagent to derivatives of ethyl but-Zynoate bearing the appropriate
functional group at C-4.
Several interesting studies have been directed towards the synthesis of insect
pheromones (see also ref. 174). (3R)-( +)-Frontalin (67), an aggregation factor of
beetle species which can be regarded, at least from the synthetic viewpoint, as a
bis-nor-monoterpene, has been obtained (25 % ;five steps) from (3R)-(-)-linal~ol:~*~
the key step was (68)+(69) using the reagent Me,SiCMe(Li)Cl; this, as a source of
carbanion in carbonyl addition followed by intramolecular displacement of
chlorine, would seem an important general route to a,P-epoxysilanes. The diol
(70), a butterfly pheromone, has resulted from geraniol by site-specific olefin
functionalization and the subsequent anionic (2,3)-sigmatropic rearrangement of
the methoxycarbonylethylallylic sulphide.lS3 Other insect pheromones of diverse
size (C&-C29)
have been synthesized using citronellol, citronellal, or citronellic
R
0 NMe,
0 NMe,
xy
(71)
176
177
178
1'9
180
181
----+
a,
(72)
(73) X
C0,H or C0,Et
T. Kato and 1. Ichinose, J. Chem. SUC.,

Perkin Trans. I , 1980, 1051.
T. Kumagai, F. Ise, I. Uyehara, and T. Kato, Chem. Lett., 1981, 25.
D. J. Morgans, K. B. Sharpless, and S. G. Traynor, J. Am. Chem. SOC.,1981, 103,462.
M. B. Erman, L. V. Shmelev, I. M. Pribytkova, and I. S. Aulchenko, Zhr. Org. Khim., 1979, l!~,
1598.
Y. Stenstrou and L. Skattebol, Actu Chem. Scund., Ser. B. 1980, 34, 131.
C. D. Poulter, P. L. Wiggins, and T. L. Plummer, J. Org. Chem., 1981, 46, 1532.
P. Magnus and G. Roy, J. Chem. SOC.,Chem. Commun., 1978, 297.
Y. Masaki, K. Sakuma, and K. Kaji, Chem. Lett., 1980, 1061.
Monoterpenoids
21
acid as chiral source^.'*^-^^^ p-Sinensal (which exhibits JH activity) was prepared

from myrcene; the last steps utilized a possibly general reaction whereby a thioncarbamate (71) was rearranged in situ to an allylic thiolcarbamate (72), which could
be functionalized to give an (E)-product (73).18'
Many reports concern homologization or coupling of monoterpenes to give
non-terpenoid products. Of especial interest are the reactions of allyl formates with
Wittig reagents to give substituted allyl vinyl ethers, e.g. (74)+(75), which can
undergo Claisen rearrangement to y,bunsaturated carbonyl compounds (76),188
focHo
(74)
-;"'
PhaPCHPh
-Ph
(75)
(76)
and the reaction of isolinalool (77) to give (78).lS9Citronellyl acetate (79) coupled
with acetylenic esters in the presence of AlC13 to give (80), and the use of ethylaluminium dichloride as a catalyst allowed the isolation of pure products from
acid-sensitive alkenes.lgoMe,Cu,Li, (prepared from CuI and MeLi-LiC1)converted
a,P-unsaturated aldehydes such as geranial efficiently into @-methylaldehydes and,
unlike Me,CuLi, it usually gave a negligible amount of the 1,2-adduct (l-methylgeraniol) even when a quaternary carbon was generated in the reaction.lgl Other
studies have recorded the coupling of myrcene with organic acids in the presence of
sodium naphthalenidelg2and with vinyl cyanide and vinyl phenylsulphone to give
l-(4-methyl-pent-3-enyl)cyclohexenes1g3~1g4
and reaction of citral with substituted
acetophenones to give, e.g. (81),lg5with allyl iodide (SnF, catalyst) to give chain
extension at C-1,1g6with bis-anions derived from furoic acid to give (82),197 with
U. Jensen and H.-J. Schafer, Chem. Ber., 1981, 114, 292.
T. Sumki, Agric. Biol. Chem., 1980, 44, 2519.
IB6 K. Mori, S. Masuda, and T. Suguro, Tetrehedron, 1981, 37, 1329.
T. Mimura, Y. Kimura, and T. Nakai, Chem. Lett., 1979, 1361.
lS8 M. Suda, Chem. Lett., 1981, 967.
F. Naf, Ger. P., 2 849 332/1979.
1 9 0 B. B. Snider, D. J. Rodini, R. S. E. Conn, and S. Sealfon, J. Am. Chem. SOC.,1979, 101, 5283.
191 D. L. J. Clive, V. Farina, and P. Beaulieu, J . Chem. SOC.,Chem. Commun., 1981, 643.
192 T. Fujita, S. Watanabe, K. Suga, and H. Nakagama, Synthesis, 1979, 310.
198 R. V. C. Carr and L. Paquette, J. Am. Chem. Soc., 1980,102,853.
194 0. P. Vig, I. R. Trehan, G. L. Kad, and A. L. Bedi, IndianJ. Chem., Sect. A , 1979,17,555.
S. Y.Dike and J. R. Merchant, Indian J . Chem., Sect. B., 1978, 16, 1111.
T. Mukaiyama, T. Harada, and S. Shoda, Chem. Lett., 1980, 1507.
D. W. Knight, Tetrahedron Lett., 1979, 469.
184
22
p-
carbazoles to give pyran0[2,3a]carbazoles,19~and with dihydroxycoumarones to

give (amongst others) an intermediate en route to e r i o b r u c i n ~ l . ~ ~ ~
OAc
HC = CC0,Me
(79)
(80)
Reactions with Metal Complexes.-Pd (mainly Pd") complexes catalyse or otherwise

mediate several synthetically useful processes. Myrcene with aqueous [(MeCN),PdC12] yielded (83) + (84) which on basification gave nerol and citral, but no
geranio1.200The same complex catalysed the conversion of linaloyl acetate into
neryl and geranyl acetates in low yield, but 6,7-dihydrolinaloyl acetate was very
effectively (90 %) isomerized.201Geranyl and neryl acetates underwent hydrogenolysis with PdO and ammonium formate to give largely unrearranged 1-olefins,2O2
and the same substrates were converted with regio- and stereo-control into allylic
p-tolyl sulphones by sodium p-tolylsulphinate and [Pd(PPh3)4].203Pd and Ni
(83)
lS8
lSs
(84)
(85) X
S0,Ph or C0,Me
D. P. J. Patel, Synth. Commun., 1981, 11, 823.

L. Crombie, S. D. Redshaw, D. A. Slack, and D. A. Whiting, J . Chem. Soc., Chem. Commun.,
1979,628.
2oo
202
*03
(86)
M. Takahashi, H. Suzuki, Y. Moro-Oka, and I. Ikawa, Chem. Lett., 1979, 53.

L. E. Overman and F. M. Knoll, Tetrahedron Lett., 1979, 321.
J. Tsuji and T. Yamakawa, Tetrahedron Lett., 1979, 613.
K. Inomata, T. Yamamoto, and H. Kotake, Chem. Lett., 1981, 1357.
Monoterpenoids
23
complexes catalysed the alkylation of myrcene with NaCH(C0,Me)2,204and this

reagent or NaCH(SO,Ph)CO,Me alkylated geranyl acetate in the ally1 positions in
the presence of PdO complexes to give (85) and small amounts of (86).205Geranyl
derivatives (87) [X = acetate, halogen, OAlR,, OPO(OR),, or OSiR,] coupled with
dimethylalkenyl aluminium compounds, e.g. to give (88).,06
Oxidation and Reduction.-Geraniol on treatment with t-butyl hydroperoxide and
Ti catalysts in the presence of ( +)-diethy1tartrate gave the (2S,3S)-oxide,whereas
t-Butyl
in the presence of the (-)-tartrate the other isomer was
hydroperoxide and vanadium catalysts converted (R)-(-)-linalool into 2,3epoxycitronellol (89), which on reduction and photosensitized oxidation yielded
(93)
(94)
(90) : this was cyclized to two products which were separately dehydrated to nerol
oxide (91) and its enantiomer, each in 95 % optical purity.20sNerol oxide from rose
oil is racemic and it was suggested that this was produced by the direct photoxidation of nerol [natural (-)-rose oxide is believed to be similarly produced from
( -)-citronellol]. The rose oxide was also converted into sesqui-rose oxides.208a
Epoxidations, carbene additions, etc. of 2,3-epoxycitral have been
A very detailed investigation of the dye-sensitized photoxidation of a-nerol (92)
showed the formation of the diols (93) and (94) with no cyclized products.210
Allo-ocimene and myrcene on autoxidation in DMF or DMSO give an odd variety
*04
*05
*06
*07
ao8
R. Baker and R. J. Popplestone, Tetrahedron Lett., 1978, 3575.

B. M. Trost and T. R. Verhoeven, J . Am. Chem. SOC.,1980,102,4730.
E. Negishi, S. Chatterjee, and H. Matsushita, Tetrehedron Lett., 1981, 22, 3737.
T. Katsuki and K. B. Sharpless, J. Am. Chem. SOC.,1980, 102, 5974.
G. Ohloff, W. Giersch, K. H. Schulte-Elte, P. Enggist, and E. Demole, Helv. Chim. Acta,
1980,63, 1582.
G. Ohloff, W. Giersch, R. Decorzant, and G. Biichi, Helv. Chim. Actu, 1980,63, 1589.
L. P. Glushko, V. N . Samsonova, M. S. Malinovskii, and L. A. Yanovskaya, Zsv. A k d . Nauk
SSSR, Ser. Khim., 1980, 1048.
*lo K. H. Schulte-Elte, B. L. Mulier, and H. Pamingle, Helv. Chim. Actu, 1979, 62, 816.
*Ow
*09
24
OH
(95)
R'
R'
(97)
R'
(98)
(99)
of products,211and geranic acid was formed in 92% yield from citral by sodium
chlorite in the presence of 2-methyl-but-2-ene (a C1. scavenger).212Benzyl ethers of
nerol were oxidized at the 6,7-bond to give poor yields of products required as
intermediates for the synthesis of the antibiotic moenocinol, but epoxidation and
conversion into the sulphone (95) allowed epoxidation to (96) in good (60%)
yields.213
Electrochemical oxidations have been previously mentioned.122A novel application is the regioselective epoxidation (80 % conversion ; 90 % selectivity) at the 6,7bond of geranyl and neryl esters and phenyl ~ u l p h o n e sAnother
. ~ ~ ~ is the one-step
conversion of olefins into allylic alcohols via electrooxidative-oxyselenylationdeselenylation, e.g. (97)+(99). This method has been applied to the synthesis of
(100) which can be converted (70%) into marmelolactone [(101) from quince], and
h0-r+
0
MeSO&l-Et.N
ho0
(100)
to the synthesis of rose oxide (102) from citronellol (103).215[l-2H]Citralcould be

reduced to [l-2H]geraniol with an optical purity of 90 % by use of a chiral complex
aluminium hydride.21aIsotopically normal citral was efficiently reduced to geraniol
211
212
213
214
216
?16
M. Nomura, Y. Fujihara, and Y. Matsubara, Nippon Kogaka Zaishi, 1980, 779.

B. S. Bal, W. E. Childers, and H. W. Pinnick, Tetrahedron. 1981, 37, 2091.
P. J. Kocienski, J . Org. Chem., 1980, 45, 2037.
S. Torii, K. Uneyama, M. Ono, H. Tazawa, and S. Matsunami, TetrehedronLett., 1979, 4661.
S. Torii, K. Uneyama, and M. Ono, TetrahedronLett., 1980, 21, 2653.
M. Nishizawa and R. Noyori, Tetrahedron Lett., 1980, 21, 2121.
Monoterpenoids
25
(W
Reagents: i, Ni(OAc),NaBH,;
ii, ROCl; iii,
;iv, CuBr-PBr,, -78C
scheme 6
with no 1,6addition by EtCH(OMgBr)2217or to citronellol over metallic catalysts.218-220Geraniol and nerol were reductively deoxygenated with preservation of
the E- or 2-geometry by LiAlH, and [Cp2TiC12]as catalyst.221Dehydrolinalool was
effectively reduced over Pd to l i n a l o 0 1 , ~as~was
~ ~ geranic
~ ~ ~ acid to dihydrogeranic
acid over K-gra~hite.~~*
The trimethylsilyl group continues to be used as a protecting or directing group in synthesis, viz. the sequences (104)+( 105)225and ( 1 0 6 ) j
(107) (Scheme 6).226Also, a variety of A2-butenolides may be synthesized via
oxidation of the 0-trimethylsilylcyanohydrinsof ct,p-unsaturated aldehydes with
pyridinium dichromate in DMF, cf. (108)-+(109).227
Cyclizations, Isomerizations, etc.-(See also rose oxidezo8).Citral on irradiation at
relatively elevated temperatures ( > 80 "C) gave two new products (1 10a and b)
(5-10%) and a biradical route was proposed. It was demonstrated that these
products did not arise from cleavage of (1 1l), a previously known product of the
reaction: the latter gave (1 12) and (1 13) under these conditions.228A more detailed
*17
J. H. Babler and B. J. Invergo, TetrahedronLett., 1981, 22, 621.

D. V. Sokolskii, A. M. Pak, and S. R. Konuspaev, Zh. Prikl. Khim., 1981, 51, 1145.
D. V. Sokolskii, A. M. Pak, S. M. Turganbaeva, S. R. Konuspaev, and M. A. Ginzburg,
Zh. Prikl. Khim., 1981, 54, 1574.
A. M. Pak, S. R. Konuspaev, and D. V. Sokolskii, Kinet. Catal. Lett., 1981, 16, 339.
F. Sato, Y. Tomuro, H. Ishikawa, T. Oikawa, and M. Sato, Chem. Lett., 1980, 103.
A. M. Pak, D. V. Sokolskii, 0. I. Kartonozhkina, and R. E. Kumetsova, Dokl. Akad. Nauk
SSSR, 1980, 253, 170.
A. M. Pak, D. V. Sokolskii, 0.I. Kartonozhkina, 0.V. Vyaznikovtseva, and E. N. Lituyakova,
Zh. Prikl. Khim., 1980, 53, 2065.
M. Oontento, D. Savoia, C. Trombini, and A. Umani-Ronchi, Synrhesis, 1979, 30.
R. Calas, J.-P. Pillot, and J. Dunogues, C. R. Hebd. Seances Acad. Sci., Ser. D, 1981,292,669.
A. Yasuda, S. Tanaka, H. Yamamoto, and H. Nozaki, Bull. Chem. SOC.J., 1979, 52, 1752.
E. J. Corey and G. Schmidt, TetrahedronLett., 1980, 21, 731.
S. Wolff, F. Barany, and W. C. Agosta, J. Am. Chem. SOC.,1980, 102,2378.
lao
*28
2Z4
a25
aa7
26
po
j
?
o
(110a)
+CHO
E C H O
(1lab)
&\
CHO
study showed that on 'n,x* excitation (A > 347 nm) the products were (1 11) and
(1 14), whereas on %,x* excitation (A = 254 nm) (1 14) and (1 1 9 , but not (1 1l),
were formed. An intramolecular [2 + 21 photocycloaddition that was shown to be a
triplet process was found on h,x* or lx,x* excitation of (1 16) to give (1 17) only,
whereas broad-spectrum irradiation (A > 280 nm) of (1 17) gave isomers of (1 18)
which photoisomerized to the oxetans (1 19).229Irradiation of citronellyl iodide
gave citronellene and various m e n t h e n e ~ . ~ ~ ~
Lao
M. Yoshioka, K. Ishii, and H. R. Wolf, Helv. Chim. Acta, 1980, 63, 571.
K. M. Saplay, R. Sahui, N. P. Damodaran, and S. Dev, Tetrahedron, 1980,36, 1455.
Mono terpenoids
I
27
Hp$-JH
HO
(123)
( 124)
Several new, or adaptations of old, cyclizations to furan and pyran derivatives
have appeared. Geranyl acetate with RuOl gave the isomers of (120)and also (121)
(51 % and 12 %),231 A more stereocontrolled synthesis yielded the bis-tetrahydrofurans (122)and (123)containing four chiral centres (each in 90% isomeric purity)
in a four-step route from geranyl or neryl chlorides that involved two stereoselective
cyclizations. The epoxide ring of (123) could be opened by an allylic Grignard
reagent and the resulting product dimerized to give (124).232
Two new routes to rose
oxide have been claimed; one from citronellyl acetate233and the other from cyclization of 3,7-dimethylocta-(Z)2,5,7-triene,which can be easily obtained from iso~rene.~~~
An elegant stereocontrolled synthesis of the cis- and trans-linalool oxides (125)

has been developed involving iodocyclization of 2,6-dimethylocta-(E)6-ene-2,3-diol:
the cis-isomer was favoured on steric grounds.? The isomers (125) were also
formed in an alleged biogenetic-type ( !) process from 6,7-epo~ylinalool.~~~
Hydroxylated linalool derivatives have been demonstrated as likely precursors for (I 25), its
dehydration products, and other furanoid and pyranoid compounds formed on
heating g r a p e j u i ~ eLinalool
. ~ ~ ~ was cyclized by HgOAc to give (126)but demercura231
232
233
234
236
z36
437
P. H. J. Carlsen, T. Katsuki, V. S. Martin, and K. B. Sharpless,J . Org. Chem., 1981,46,3936.

A. Amouroux, G. Folefoc, F. Chastrette, and M.Chastrette, Tetrahedron Lett., 1981, 22,2259.
S. G. Hegde and seven others, Tetrahedron Lett., 1980, 21, 441.
T. Yamato and N. Nakamura, 7th International Congress on Essential Oils, pp. 287, 997
(Chem. Abstr., 1980, 92, 129 093).
S. D. Rychnovsky and P. A. Bartlett, J . Am. Chem. SOC.1981,103, 3963.
T. Kametani, H. Nemoto, and K. Fukamoto, Bioorg. Chem., 1978, 7 , 215.
P. J. Williams, C. R. Strauss, and B. Wilson, J. Agric. Food Chem., 1980, 28, 766.
28
tion (NaBH,) led to bicyclic ethers [e.g. (127)l. The unexpected formation of the
C-C bond is presumably due to the proximity of the Hg and the vinyl group in the
organomercurial intermediate.23s In contrast, treatment of linalool with Hg2+
salts under different conditions was claimed to lead to mainly (128).239
pq3f
I
OH
(128)
0
(131)
(132)
(129)
$q
OHC
OH
(1 30)
P (134)
O H
A detailed mechanistic study records the products of solvolysis of geranyl

chloride, phosphate, and pyrophosphate under a variety of conditions : the prevalence of cyclization or of double-bond rearrangement was correlated with the
lifetimes of the carbocations and the possibility of their achieving the most favoured
conformation^.^^^ As did most Lewis acids, Me2A1CI cyclized citronella1 to menthane derivative^.^^' Similar cyclizations of 6,7-epoxylinalyl acetate to menthanes
(after initial ring-opening with PhSeOH and treatment with F3CC02H-CH2C12)
were claimed to be biogenetic-type processes.242Treatment of allo-ocimene with
acrolein led to (129) together with some of the epimer at the carbon a to the
aldehyde group: the proportion of the latter was increased on heating.243cisOcimenol was partly converted into its trans-isomer on irradiation in the presence
of PhSSPh (presumably owing to the formation of PhS -244) and ( +)-citronello1 gave
( +)-dihydrocitronellal in the presence of [Fe(CO),] via a succession of 1,3-hydride
shifts without apparent dissociation of the
Allylic rearrangement caused by
treatment of ipsdienol (66) with HBF4 gave (130) together with dehydration
products that show pheromone activity towards Ips beetles,246and NN-dimethylgeranylamine (easily formed by base-catalysed condensation of isoprene with
dimethylamine) could readily be converted into the phenylselenide (PhSe-; Ru
catalyst), which on oxidation and rearrangement gave linalool in 83% overall
yield.247
238
23*
240
241
242
243
244
246
246
241
Y. Matsuki, M . Kodama, and S. Ito, Tetrahedron Lett., 1979, 4081.

Y. Matsuki, M. Kodama, and S. Ito, Tetrahedron Lett., 1979, 291.
C. A. Bunton, 0. Cori, D. Hachey, and J. P. Leresche, J . Org. Chem., 1979,44, 3238.
M. Karras and B. B. Snider, J . Am. Chem. SOC.,1980, 102,7951.
T. Kametani, H. Kurobe, and H. Nemoto, J. Chem. Soc., Chem. Commun., 1980, 762.
G. J. Ferber and J. A. Botten, U.K. P., 2 050 365/1981 (Chem Abstr., 1981, 95, 12 589).
K. H. Schulte-Elte, Swiss. P., 610 580/1980.
E. Weissberger, A. Stockis, D. Carr, and J. Giebfried, Buff.SOC.Chim. Belg., 1980, 89, 281.
W. Francke, P. Saverwein, J. P. Vile, and D. Klimetzet, Naturwissenschaften 1980, 67, 147.
S. I. Murahashi and T. Yano, J . Am. Chem. SOC.,1980,102,2456.
Mono terpenoids
(136)
29
(137)
(138)
(139)
(140)
Nerol was cyclized on treatment with Tl(ClO,), to 6-oxabicyclo[3.2.1]octane

derivatives (131) and (132):248it had previously been shown (in 1976) that geraniol
gave 6,9-dioxabicyclo[3.3.1Inonane derivatives under the same conditions. Similar
reactions of citral led to a novel 6,8-dioxabicyclo[3.2.l]octane (133) that has the
skeleton of certain pheromones of bark beetles.249Nerol and related (Z)-allylic
alcohols could be cyclized with Tic,-PhNHMe complex. Nerol yielded a-terpinyl
chloride, whereas (134) gave (135) : chlorine in the latter could not be displaced in
SN2reactions but conversion into the Bu",Sn derivative and oxidation gave (136),
which could be readily elaborated to nezukone (137).250Cycloheptyl compounds
[e.g. (138)] could also be made by hydroboronation and cyanidation of linaloyl
acetate or by carbene addition to p i p e r i t e n ~ n eCyclo-octyl
.~~~
ketones [e.g. (140)]
resulted from cyclization of the enol form of (E)-ocimenone ( 1 39).252
5 Tetramethylcyclohexanes and Related Compounds

Safranal (141) was formed by cyclization of (142) and functionalization. The
intermediate was obtained by treatment of the epoxide of geranyl acetate with
PhSe-.253Cationic cyclization of geranyl cyanide and related compounds via their
bromohydrins gave isomeric products (143 ; R = CH2CN) that could be modified
to give certain marine natural products, e.g. [143;R = CH,C(Me)OHCH=CH2].2S4
Dimethylgeranylamine (cf. ref. 247) was cyclized by 40 % H2S04to (144) whereas
treatment of the diethylamine with BF, etherate gave the exo-isomer. Treatment of
24t3
35O
251
z62
263
854
Y. Yamada, H. Sanjoh, and K. Iguchi, Tetrahedron Lett., 1979, 1323.

Y. Yamada, H. Sanjoh, and K. Iguchi, Tetrahedron Lett., 1979, 423.
T. Saito, A. Itoh, K. Oshimo, and H. Nozaki, Bull. Chem. SOC.J . , 1981, 54, 1456.
R. Murphy and R. H. Prager, Aust. J. Chem., 1981, 34, 143.
R. C. Cookson, S. Sakdarat, and M. Webster, J. Chem. SOC.,Chem. Commun., 1980, 281.
T. Kametani, K. Suzuki, H. Kurobe, and H. Nemoto, Chem.Pharm. Bull., 1981,29,105.
A. Murai, A. Abiko, K. Kato, and T. Masumune, Chem. Lett., 1981, 1125.
30
(144) with ethyl chloroformate gave (145), whereas conversion of the exo-isomer
into the amine oxide and Cope elimination formed (146).255-256 Two elegant
(150)
Reagents: i, Me,C=CHCH,Br; ii, SnCI,; iii, NaH; iv, ClPO(OEt),;
v, LiMe2Cu; (iii, iv: conversion to enol phosphate); vi, HC0,Et-NaH
Scheme 7
/,iii-v
(151)
Reagents: i, H,-Pd; ii, HN0,-AcCH; iii, KOH; iv, H+; v, LiAlH,; vi, BunLi;
vii, TiC1,-LiAlH, ; viii, 1-methyl-2-fluoropyridinium salts
Scheme 8
25b
eaa
K. Takabe, T. Yamada, and T. Katagin, Chem. Ind. (London), 1980, 540.

K. Takabe, T. Yamada, T. Sato, and T. Katagin, J . Chem. SOC.J., Ind. Chem. Sect., 1980,
776.
Monoterpenoids
31
pathways to interesting and potentially synthetically useful intermediates based on

the 1,1,2,3-tetramethylcyclohexane skeleton are (147)+( 148)257and (149)+( 150)
(Scheme 7);258paths to related diene and monoene esters have also been developed.259-261
An impressive route has been established to karahara ether (151) (Scheme
8):262 the last dehydration with ring closure by use of a 1-methyl-2-fluoropyridinium salt is especially noteworthy.
FCyclocitral (152) has been converted into ~ h l o r o -and
~ ~ lactonized
~
comp o u n d the
~ ~a-isomer
~~
has been f u n c t i ~ n a l i z e dand
~ ~used
~ as starting material for a
synthesis of a-damascones.266Thirteen new halogenated and oxygenated monoterpenes with the I 1-dimethyl-3-ethylcyclohexaneskeleton [so-called ochtodane
(153)] have been isolated from red marine
and a weevil pheromone (154)
has been synthesized from dimedone using ethoxyvinyl-lithium(a new acetaldehyde
equivalent).268 2,4,4,5-Tetramethylcyclohex-2-en-l-oneoccurs in rhizomes of
iris.269 A compound from Curium spp. is p-cyclolavandulic acid (2,4,4-trimethylcyclohex- 1-en-l-oic acid), not a keto-acid as previously reported.268aNor-monoterpenes, e.g. 3,5,5-trimethylcyclohex-2-en-l-one,were oxidized at the allylic
positions by cultures of Aspergillus species.27o
F. W. Sam and L. Weiler, J. Am. Chem. SOC.,1979, 101,4401.

D. Gullerm, G. Boussac, J. Lalande, P. Lemaitre, and J.-Y. Lallemand, Synth. Commun., 1981,
11, 627.
a69
m0
e61
26z
263
864
266
26e
269
F. Rouessac and H. Zamarlik, Tetrahedron Lett., 1979, 3417.

M. Alderice and L. Weiler, Can. J. Chem., 1981, 59, 2239.
I. Kitagawa, and seven others, Chem. Pharm. Bull., 1981, 29, 2548.
T. Mukayama, N. Iwasawa, T. Tsuji, and K. Narasaka, Chem. Lett., 1979, 1175.
S. G. Hegde and J. Wolinsky, Tetrahedron Lett., 1981, 22, 5019.
A. W. Frank, J. Heterocycl. Chem., 1981, 18, 549.
R. Pelliciari, E. Castognino, R.Friguelli, and S. Corsano, Tetrahedron Lett., 1979, 481.
H. J. Liu, H. K. Hung, G. L. Mhehe, and M. L. D. Weinberg, Can. J. Chem., 1978,56,1368.
V,J. Paul, 0. J. McConnell, and W. Fenical, J. Org. Chem,, 1980, 95, 3401.
R. H. Wollenberg and R. Peries, Tetrahedron Lett., 1979, 297.
A. Sattar, M. Ashref, M. K, Bhatty, and N. H. Christi, Phytochemistry, 1978, 17, 559.
J. Garner0 and D. Joulain, Bull. SOC.Chim. Fr., Part IZ, 1979, 455.
Y. Mikami, Y. Fukunaga, M. Arita, Y. Obi, and T. Kisaki, Agric. Biol. Chem., 1981,445, 791.
32

6 The Menthane Class
General.-Reviews,
some unfortunately badly out-of-date, have appeared on
p-menth- 1-ene,271~ - m e n t h - 3 - e n em-menthane
,~~~
derivatives,273dihydrocar~one,~74
P - t e r p i n e ~ land
, ~ ~on
~ aspects of the chemistry of a ~ c a r i d o l eThe
. ~ ~enantiomers
~
of
(155), together with products of cleavage of the dioxide bond (but no a~caridole),~~
1-hydroxy- and 1,4-dihydroxy-derivativesof ~ - m e n t h - 2 - e n e other
, ~ ~ ~ oxygenated
p - m e n t h e n e ~ ,and
~ ~ ~various 2-nitro-p-rnenthadiene~~~O
have been isolated from
assorted plants.( -)-Mint lactone (156) and its epimer at C-3 occur in Mentha spp.
and have been prepared by oxidation of menthofuran.281More extensively functionalized p-menthanes, e.g. (1 57),282(1 58) (R= Et or Pri),283and 1-vinyl-p-menth-4(8)ene284also occur naturally. Two new glucosides [schizonepetosides (1 59 ; isomers)]
occur in Schizonepeta s p ~ .and
, ~ menthyl-p-D-glucosides
~ ~
were found in Mentha
spp. :z8s the latter have been prepared and the isomers separated by g.c. of acetyl
derivatives.287Pyrolysis of an incense derived from Boswelliu spp. gave (160) and
fiH
(159)
QPh 0
II
271
279
275
270
277
478
279
280
281
283
284
28s
280
J. Verghese, Perfum. and Flavorist, 1980, 5, 18.

J. Verghese, Perfum. and Flavorist, 1980, 5 , 39.
M. Balci, Chem. Rev., 1981, 81, 91.
J. de Pascual, I. S . Bellido, C. Torres, B. A. Sast,e, and M. Grande, Phyrochemistry, 1981, 20,
163.
H. P. Schenk and D. Lamparsky, J . Chromatogr., 1981, 204, 391.
J. M. Sendra and P. Cunat, Phytochemistry, 1980, 19, 89.
S . Escher, U . Keller, and B. Willhalm, Helv. Chim. Acta, 1979, 62, 2061.
K. Takashashi, T. Someya, S. Muraki, and T. Yoshida, Agric. Biol. Chem., 1980, 44, 1535.
F. Bohlmann, C. Zdero, and A. G. R. Nair, Phytochemistry, 1979, 18, 1062.
A. F. Thomas, M. Schouwey, and J. C. Egger, Helv. Chim. Acta, 1981, 64, 1488.
S . B. Singh, A. Goswami, M. C. Nigam, and R. S . Thakur, Phytochemistry, 1980, 19, 2466.
H. Sasaki, H. Taguchi, T. Endo, I. Yosioka, and Y . Iitaka, Chem. Pharm. Bull., 1981,29,1636.
I. Sakata and K. Koshimizu, Agric. Biol. Chem., 1978, 42, 1959.
I. Sakata and H. Iwamura, Agric. Biol. Chem., 1979, 43, 307.
Monoterpenoids
33
related corn pound^.^^^^^^^ The optical properties (c.d. etc.) of conjugated cisoid
dienss, and enones including pulegone and cx-phellandrene, have been studied.O
A menthofuran derivative was a main constituent of an Anethum species:291menthofuran itself has been efficiently synthesized from a - p ~ l e g o l p
, ~u~l e~ g 0 n e , ~ ~or~ ~ ~ ~ 4
2-carboxyethyl-5-methylcyclohexanone.295A synthesis of the related (R)-(-)evodone (161) from (R)-(+)-citronellic acid confirmed the natural isomer to the (R)c o m p o ~ n d96. ~
A mixture of o-menthanes resulted from reduction of o-cymene with Ca(NH3),,2S7
and a neat route to the o-menthane skeleton involved photochemical addition of
allene to 3-methylcyclohex-2-en-1-one and opening of the cyclobutyl ring with
BF3.2980-Menthadi- and tri-enes resulted from pyrolysis of ~ e r b e n e n e . Acid~~Q
and base-promoted isomerizations of o-menthadienes300 and dehydration of
cis- and trans- o-menthan-8-01s with a variety of reagents have been re~orded.3~1
Optically active 2-methyl-4-isopropenylcyclohexanone(which is a useful precursor
for rn-menthane derivatives) has been prepared by pyrolysis of chiral2,2,5-trimethylbicyclo[3.1.l]heptan-2-0ne.~~~
Formation of the Menthane Skeleton.-Isoprene cyclodimerized in the presence of
Ni303 or Fe304$305
catalysts to mixtures of m- and p-menthadienes, 1,4-dimethyl-4vinyl- and 1,3-dimethyl-3-vinyl-cyclohexenes,and
dimethylcyclooctadienes. An improved synthesis of piperitone from mesityl oxide and methyl
vinyl ketone has been devised,306and the latter condensed (NaH) with methyl
2-methyl-1-carboxymethylpropyl ketone to yield (162), which could be cyclized
under appropriate conditions to give excellent ( > 80 %) yields of either 0- or p men then one^.^^' Myrcene yielded p-cymene on heating with metal
( +)-citronella1 was selectively cyclized to (-)-isopulegol by Zn halides,309and the
288
M. Pailer, 0. Scheidl, H. Gutwillinger, E. Klein, and H. Obermann, Monatsh. Chem., 1981,

112, 595.
289
M. Pailer, 0. Scheidl, H. Gutwillinger, E. Klein, and H. Obermann, Monarsh. Chem., 1981,

112, 987.
280
293
D. A. Lightner and six others, J . Am. Chem. SOC.,

1981, 103, 5314.
P. Schreier, F. Drawert, and I. Heindze, Lebensm. Wiss. Technol., 1981, 14, 150.
Z. U. Din, T. L. Ho, and S. G. Traynor, U.S. P., 4 240 969/1980 (Chem. Abstr., 1981, 95,
7510).
T. Sato, M. Tada, and T. Takahashi, Bull. Chem. SOC.

J., 1979, 52, 3129.
S. C. Taneja, K. L. Dhar, and C. K. Atal, Indian J. Chem., Sect. B, 1980, 19, 714.
2S5 S. Tsubio, K. Shimozuma, and A. Takeda, J. Org. Chem., 1980, 45, 1517.
286 Y. Masaki, K. Sakuma, K. Hashimoto, and K. Kaji, Chem. Lett., 1981, 1283.
2 e 7 V. V. Bazylchik, P. I. Fedorov, and N. M. Ryabushkina, Zh. Org. Khim., 1978, 14, 969.
z88 D. K. M. Duc, M. Fetizon, I. Hanna, and S. Lazare, Synthesis, 1981, 139.
2nQ V. V. Bazylchik, P. I. Fedorov, E. D. Skatovski, and L. I. Vinogradov, Zh. Org. Khim., 1981,
293
ZQ4
17, 320.
300
301
302
303
304
305
306
307
308
30s
V. V. Bazylchik and P. I. Fedorov, Zh. Org. Khim., 1979, 16, 1422.

V. V. Bazylchik and E. I. Ionova, Zh. Org. Khim., 1978, 14, 538.
A. Yoshikoshi, K. Takagi, T. Nishimura, M. Iwamoto, and K. Kojo, Jap. P., 132 541/1978.
P. W. N. M. van Leeuwen and C. F. Roobeck, Tetrahedron, 1981, 37, 1973.
E. Leroy, D. Huchette, A. Mortreux, and F. Petit, Nouv. J . Chem., 1980, 4, 173.
R. Petiaud and Y. B. Taarit, J. Chem. SOC.,Perkin Trans. I , 1980, 1385.
0. Namanishi, M. Fusitani, I. Ichimoto, and H. Ueda, Agric. Biol. Chem., 1980, 44, 1667.
W. Kreiser and P. Below, Tetrahedron Lett., 1981, 22,429.
M. A. Ryoshentseva, E. P. Belanova, K. M. Minachev, M. M. Emelyanov, and A. V. Semenovski, Izv. Akad. Nauk SSSR,Ser. Khim., 1980, 1659.
Y. Natakani and K. Kawashima, Jap. P, 11 648/1978 (Chem. Abstr., 1979, 90, 876494).
34
bisulphite compound of citra1310or the PhSeOH adduct (at C-6 to C-7) of linaloyl
acetate311 (cf. ref. 242) readily cyclized to p-menthane derivatives. Long-term (8
months) treatment of citral with HCl gave a variety of oxygenated derivatives of
p-cymene and of piperitone that were responsible for the odour of deteriorated
lemon oil?, The benzylimine derived from citronellal was cyclized by SnCl, to give
(after reduction and debenzylation) menthylamine together with its neo- and
neo-iso-isomers (75 % total; 7: 1: 2):312athis shows that an imido function can
initiate acid-catalysed cyclization of polyenes, and an additional advantage of the
method is that chirality may be introduced by reason of a chiral group linked to N
(e.g. 36 % chiral induction when chiral citronella1 was used).
More defined rou+te_shave been developed to specific compounds. Use of five
equivalents of Me,PCH, under 'salt free' conditions (necessary) converted 4carboxyalkylcyclohexanones into p-menth- 1(10),7-diene.,13 An example of a
general ketone to enone homologation is the reactign of 4-methylcyclohexanone
with the anion from alkylchlorosulphoxides [R(Cl)CSOPh] to yield (after intramolecular displacement of C1) the epoxide (163), which on pyrolysis gave (164) that
could be easily converted into p-menth-3-en-8-01.~~~
A highly stereoselective route
to both diastereoisomers of p-menth-1 -en-Pol was developed using kinetically
controlled alkylations and epimerization of the lactone (165) to control the stereochemistry :315 the intermediate was synthesized from 6-methylcyclohex-2-en-1-01.
Silyl-Li reagents mixed with Cu' salts reacted with enones to give @-silylketones
in good yield. These could be used in synthesis without risk to the silyl groups and
the enone grouping could be restored by bromination-desilylbromination with
CuBr,. The method is illustrated by an efficient synthesis of carvone (166) (Scheme
9).3l6
Jiii, iv
y&L
PhMe,Si*
(166)
Reagents: i, (PhMe,Si),CuLi; ii, MeI; iii, MeLi; iv, H,O+;
V,
CuBr2-(PhC02), vi, Ac20
Scheme 9
alo
M. B. Erman, L. V. Shmelev, I. M . Pribytokova, and I. S. Aulchenko, Zh. Org Khim., 1979,

15,1598.
sll
312
alea
313
314
s16
T.-Kametani,H. Kurobe, and H. Nemeto, J . Chem. SOC.,Perkin Trans. I 1981, 756,

K. Kimura, E. Doi, H. Nishimura, and I. Iwata, J . Agric. Chem. SOC.Jpn., 1981, 55, 1073.
G. Demailly and G. Solladie, J . Org. Chem., 1981, 46, 3102.
A. P. Uijttewaal, F. L. Jonkers, and A. van der Gen, J . Org. Chem., 1979,44, 3157.
D. F. Taber and B. P. Gum, J. Org. Chem., 1979,44,450.
P. A. Bartlett and C. F. Pizzo, J. Org. Chem., 1981, 46, 3896.
D. J. Ager, I. Fleming, and S. K. Patel, J. Chem. SOC.,Perkin Trans. I , 1981, 1510.
Monoterpenoids
35
Another impressive use of silyl reagents came in the sequence leading to 8terpineol (167).,17 Homologation of 5-methylcyclohex-2-en-1-onecatalysed by
FeO complexes led (after appropriate functionalization) to menthone and isom e n t h ~ n ewhereas
, ~ ~ ~ Pd'I-catalysed coupling of 2-bromopropene with l-methylcyclohexa-1,3-diene gave p-mentha- 1,3,8-triene
Treatment of a-pinene
with Bz,02 and Cu' salts gave the benzyl derivative of trans-carveol, which could
be converted into carvone in 46% overall yield:320the phenylurethane of pinol
formed (1 68) on pyrolysis.321
II
C0,Me
II
C0,Me
OH
(168)
(167)
Oxidation, Reduction, and Related Reactions.-Anthem01 (169) which has hardly

been reported since its claimed discovery in 1879 has been synthesized (44 %) in a
one-pot (presumably general) metallation of a-terpinene (BuLi-ButOK), followed
by reaction with fluorodimethyloxyborane and oxidation (alkaline KMn04).322
6-Terpinene and other non-conjugated p-menthadienes were quantitatively
aromatized by KMnO,-C,H,-crown
ether, whereas the conjugated isomers (e.g.
a-terpinene) were unaffected.323Ammonoxidation of limonene (NH, + 0,;
Fe or
U-Sb catalysts) gave various terpinenes, pulegones, and trimethylpyridines ( !):
the intermediacy of such as (170), which cyclized to, e.g., (171) and (172) was
Oxidation of limonene with Pb(OAc), led to (173; 82%), which is a
component of Bulgarian rose oi1,325932sin contrast, hydroboration (BH,Cl) and
oxidation gave (174).327Quinquevalent organobismuth reagents (e.g. Ar,BX,;
X = ester or halogen) oxidized allylic alcohols under mild conditions: thus carveol
gave ~ a r v o n e . ~ ~ ~
Pulegone and menthone formed (1 75) and (1 76) respectively on autoxidation in
alkaline media.329Pulegone also underwent a conventional Baeyer-Villiger oxidation
317
318
31g
320
321
322
323
324
386
386
327
S. R. Wilson, L. R. Phillips, and K. J. Natalie, J. Am. Chem. SOC.,1979, 101, 3340.

T. C. T. Chang and M. Rosenblum, J. Org. Chem., 1981, 46,4103.
B. A. Patel, L. C. Kao, N. A. Cortese, J. V. Minkiewicz, and R. F. Heck, J . Org. Chem., 1979,
44,918.
W. Liang-Liu and Y. S. Cheng, Proc. Natl. Sci. Counc. Repub. China, 1980, 5, 21.
H. Starzemska and K. Piatkowski, Pol. J . Chem., 1980, 54,939.
M. Schlosser, M. Bosshardt, A. Walde, and M. Stahle, Angew. Chem. Znt. Ed. Engl., 1980, 19,
308.
A. Poulose and R. Croteau, J . Chem. SOC.,Chem. Commun., 1979, 243.
S. R. Dolhyj and L. J. Velenyi, Ind. Eng. Chem., 1980, 47, 320.
M. Nomura, Y. Fujihara, and Y. Matsubara, J . Chem. SOC.Jpn., Chem. Ind. Chem., 1979, 305.
N.Nomura, Y. Fujihara, and Y. Matsubara, Nipon Nogei Kagaku Kaishi, 1978, 1182, (Chem.
Abstr. 1979, 90, 23 274).
I. Uzarewicz and A. Uzarewicz, Pol. J . Chem., 1979, 53, 1989.
D. H. R. Barton, J. P. Kitchin, D. J. Lester, W. B. Motherwell, and M. T. B. Papoula, Tetrahedron, Suppl. 9, 1981, 37, 73.
A. Horinaka, E. Yo, 0. Mori, and K. Naya, Bull. Chem. SOC.J., 1979, 52, 2372.
36
?G
CHO
(40 % lactone formed).330 Menthone (57 %) resulted from Jones oxidation of

menthyl benzyl ether,331but (177) proved surprisingly difficult to convert into the
acid except by treatment with NaC10,.332 Conventional oxidations of the 3carboxymethyl derivative of 7,8-dih~drocarvone~~~
and of p-menth-7-en-9-01~~~
have
been recorded.
A good discussion and reference to previous results accompanies a study of the
kinetics of reaction of conjugated p-menthadienes with singlet 0,.335
Photosensitized oxidation of the isomeric trimethylsilylenol ethers of menthone yielded
p-menth- 1-en-3-one and -4-en-3-0ne,,~~
and pulegone formed (1 78) and (179) : the
former (75% yield) was reduced (PPh,) to (180). In contrast, similar oxidation
of p-menth-4(8)-ene gave only the hydroperoxide at C-4 with shift of the double
bond.337The hydroperoxides of limonene formed by ene oxidation at C-1 or C-2
have been separated and
Photo-oxidation of menth-1-ene in the
presence of FeC1, formed 1-chloro-p-menth-2-one (Cl, Pr' cis), together with
ring-opened mono- and d i - ~ h l o r i d e s . ~ ~ ~ ~ ~ ~ ~
J. R. Handley, A. A. Swigar, and R. M . Silverstein,J . Org. Chem., 1979, 44, 2954.
B. S. Bal, K. S. Kochhar, and H. W. Pinnick, J . Org. Chem., 1981,46, 1492.
332 B. S. Bal, W. E. Childers, and H. W. Pinnick, Tetrahedron, 1981, 37, 2091.
s33 H. Irie, J. Katakawa, M . Tomita, and Y. Mizuno, Chem. Lett., 1981, 637.
334 T. J. Brocksom and J. T. B. Ferreira, J . Chem. Res. ( S ) , 1980, 412.
336 B. M. Monroe, J . Am. Chem. SOC.,1981, 103, 7253.
336 E. Friedrich and W. Lutz, Chem. Ber., 1980, 113, 1245.
337 H. E. Ensley, R. V. C. Carr, R. S. Morton, and T. E. Pierce, J . Am. Chem. SOC.,
1980,102,2836.
338 B. B. Jones, B. C. Clark, and G. A. Iacobucci, J . Chromatogr., 1980, 202, 127.
339 A. Kohda and T. Sato, J . Chem. SOC.,Chem. Commun., 1981, 951.
340 T. Sato, K. Maemoto, and A. Kohda, J . Chem. SOC.,Chem. Commun., 1981, 1116.
330
331
Monoterpenoids
37
A plethora of papers records the epoxidation (both mono- and di-) ofp-menthenes
and p-menthadienes and their derivatives, and the products (usually very predictable) formed on ring-opening of the epoxides with a variety of reagents. A selection
comprises reactions of p-menth- l-ene,341p342
p-menth-7-ene (en route to p-menthenp-menth-8-en-7-01,~~
limonene,3429346-349
puleolides), 8-~hloro-p-menth-l-ene,~*~
gone,350g351
piperit~ne,~~~
carveol, 355-357 and 2,8-cineolederivatives.358
The most interesting paper of this
reports the radical-induced ringopening of the epoxide and provides a convenient alternative to the Wharton
rearrangement. As generalized from the example studied, Bun3Sn reduction
of an a,P-epoxy-o-thiolcarbonylimidazolide derivative of an alcohol led, via
(1 8 5 )
341
342
343
344
345
346
347
348
340
350
351
352
a53
s54
355
358
3J7
358
Takasago Perfumery, Co. Ltd., Jap. P., 154 929/1980 (Chem. Abstr., 1981, 94, 157 112).
K. Arata and K. Tanabe, Bull. Chem. SOC.J., 1980, 53, 299.
T. J. Brocksom and J. T. B. Ferreira, Synth. Commun., 1981, 11, 105.
R. Mestres, M. C. Polo, and M. J. Valero, An. Quim., 1979, 75,970.
T.J. Brocksom, J. T. B. Ferreira, and A. L. Braga, J. Chem. Res. ( S ) , 1981, 334.
F. Delay and G. Ohloff, Helv. Chim. Acta, 1979, 62, 2168.
R. W. Rickards and W. P. Watson, Aust. J. Chem., 1980, 33,451.
0.P. Vig, S. D. Sharma, S. S. Bori, and M. Lal, Indian J. Chem., Sect. B, 1978, 16, 739.
L. A. Mukhamedova, F. G. Nasybullina, and M. I. Kudryavtseva, Izv. Akad. Nauk SSSR, Ser.
Khim., 1979, 847.
J. Sepulveda, M. C. Polo, and R. Mestres, An. Quim., 1979, 75, 398.
A. Horunka and K. Naya, Bull. Chem. SOC.J . , 1979, 52, 1964.
A. Baragliu, G. Grandolini, C. Rossi, and C. G. Casinovi, Tetrahedron, 1980, 36, 645.
H. Orszanska, K. Witkiewicz, and Z. Chabudzinski, Pol. J. Chem., 1980, 54,45.
L. Friedman and J. G. Miller, Science, 1971, 272, 1044.
A.Yasuda, H. Yamamoto, and H. Nozaki, Bull. Chem. SOC.J., 1979, 52, 1757.
D.H. R. Barton, R. S. H. Motherwell, and W. B. Motherwell, J. Chem. SOC.,Perkin Trans.
I, 1981, 2363.
A. Itoh, K. Oshima, S. Sasaki, H. Yamamoto, T. Hiyama, and H. Nozaki, Tetrahedron
Lett., 1979, 4751.
D. Mrozinska and K. Piatkowski, Pol. J. Chem., 1980, 54, 693.
38
ring-opening, to an allylic alkoxyl radical. By a suitable choice of conditions

this could either be quenched by H transfer from the stannane or rearranged to give
more complex products [e.g. carveol gave (1Sl)]. Another significant development
is a method for the reduction of an epoxide in the presence of a carbonyl group.
The oxiran ring of (182) was opened by PhTe- or PhSe- and the resulting
product reduced with Ph,SnH under mild (25-80 "C) conditions.35Q
Ascaridole yielded the 1,2:3,4-diepoxide in the presence of a cobalt catalyst.36o
1,3,5The same product, together with a-terpineol and 2-methyl-5-isopropylhexatriene was formed on irradiation (1 85 nm) of the same substrate in cyclohexane:361
the excised oxygen all reacted with the solvent. The formation of p-menthenolides
by oxidation and lactonization of menthol derivatives362and ring-openings of
P-pinene epoxide to give perilla esters and related compounds have been recorded.363g364
Useful synthetic intermediates result from oxidative cleavage (sometimes
~*~~~
followed by degradation) of the cyclohexane rings of l i m 0 n e n e , 3 ~ diosphenol
(autoxidation in the presence of cationic micelle~),3~~
i s o p ~ l e g o l c, ~a~r ~v ~ n e , ~ ~ ~
menthone (en route to rose
a~caridole,3~l
and 1,8-cineole (mediated by a
Pseudomonas ~ p p . ) . ,The
~ ~ isopropenyl group of carvone can be effectively cleaved
off.373
Isolimonene (p-mentha-2,7-diene) was specifically reduced in the side chain

(H2 over Ru or Pd).374p375
Carvone was reduced at the endocyclic double bond by
K,[Co(CN),H] under phase-transfer catalysis (transxis-products, 6 :1),378 by
~ ~ NaBH,-p~ridine,~~~
~
or by Na-NH3NaBH,-Te (100 % t r ~ n s - p r o d u c t ) ,by
358
380
381
D. L. J. Clive and eight others, J. Am. Chem. Soc., 1980, 102,4438.

J. D. Boyd, C. S. Foote, and D. K. Imagawa, J. Am. Chem. Soc., 1980, 102, 3641.
R. Srinivasan, K. H. Brown, J. A. Ors, L. S. White, and W. Adam, J. Am. Chem. SOC.,1979,
101,7424.
B. S. Bal and H. W. Pinnick, Heterocycles, 1981, 16,2091.

363 H. Miyawaki and S. Miyazaki, Jap. P., 76 55011979 (Chem. Abstr., 1980, 92, 59 032).
384 G. Ohloff and W. Giersch, Helv. Chem. Acta, 1980, 63, 76.
365 J. Podlejski, J. Kula, and R. A. K. Riechst, Aromen, Kosmet., 1980, 30,41.
366 R. R. Heath, R. E. Doolittle, P. E. Sonnet, and J. H. Tumlinson,J. Org. Chem., 1980,45,2910.
3 1 3 ~M. Utaka, S. Matsushita, H. Yamashita, and A. Takeda, Tetrahedron Lett., 1980, 21, 1063.
SB8 K. Shankaran and A. S. Rao, Indian J. Chem., Sect. B, 1979, 18, 507.
3~ K. Tanida and K. Mori, J. Chem. Soc. Jpn., Chem. Ind. Chem., 1981, 635.
3 7 0 S. Takano, K. Masuda, and K. Ogasawara, Heterocycles, 1981, 16, 1509.
371 G.Rucker and U. Molls, Liebigs Ann. Chem., 1979, 205.
372 I. C. MacRae, V. Alberts, R. M. Carman, and I. M. Shaw, Aust. J. Chem. 1979, 32, 917.
373 S.L. Schreiber, J. Am. Chem. SOC.,1980, 102,6163,
3 7 4 J. 0. Bledsoe and C. G. Cardenas, U S . P., 4 249 028/1981.
375 J. 0. Bledsoe, U.S. P., 4 204 080/1979.
370 D. L. Rieger, M. M. Habib, and D. J. Fauth, Tetrahedron Lett., 1979, 115.
3 7 7 M. Yamashita, Y. Kato, and R. Suemitsu, Chem. Lett., 1980, 847.
3 7 e S. Raucher and K.-J. Hwang, Synth. Commun., 1980, 10, 133.
361
Monoterpenoids
39
Fe111.379It was reduced at the exo-bond by H2-[Ph3P),RhC1].3so Pulegone yielded

menthone (99 %; isomers not stated) with NaBH4-Te,377or menthone and isomenthone (3 :2) with an Ir catalyst.3s1Methods have also been worked out for the
conversion of piperitol into isomenthone using Co complexes382and for the
reduction (Na-NH,) of p-mentha-2,7-dien-9-01 to i s o l i m ~ n e n e .Liquid-phase
~~~
hydrogenation (Pd-C) of the epoxides of limonene and carvomenthene yielded
hydrocarbons and p-menthan-1-01s and -2-01s: it was deduced from a mechanistic
study that, for limonene, reaction involved an intermediate wherein the exo-double
bond had migrated into the ring.384Under similar conditions trans-1,Zdihydroxylimonene gave the dihydroxymenthane with the same configuration at C-4 as in
substrate together with its epimer (3:2): with PtO, as catalyst only the former
epimer was obtained.385Wolff-Kishner reduction of chiral carvone gave racemic
limonene and presumably involved a free carbanion as intermediate.385a
Alkylation, Homologation, and Related Processes.-Acid-catalysed (HC0,HCH2CI2)coupling of chiral limonene with 3,3-dimethylallyl alcohol gave a mixture
of C& products from which chiral a-bisabolol and epi-8-a-bisabolol could be
i~olated.~8~
Limonene condensed with methyl vinyl ketone (AlC13 catalyst) at C-9
to gave a product that could be converted into B-bisabolene (50 %).387 Carvone was
the starting material for an efficient synthesis of the sesquiterpenes P-agarofuran
and dihydroagar~furan,~~~
and also for p h y t ~ b e r i n Piperitone
.~~~
has been elaborated into the sesquiterpene ~ h y o b u n o n e and
, ~ ~ ~pulegone was ring-opened to
give dihydrogeranic acid en route to (R,R)-phyt~l,~~l
and has also been condensed
with dicyanomethane to yield Z-amin0-4,7-dimethyl-5,6,7,8-tetrahydro1-naphthalene c a r b ~ n i t r i l e Cyclobutene
.~~~
derivatives can act as isoprene equivalents in
the elaboration of Clo into C15 compounds. Thus piperitone underwent the
sequence (1 83)+( 185).393C14 compounds that should be convertible into guaiane
and eremophilane derivatives resulted from similar reactions of piperitone with the
di-TMS derivative of 1,2-dihydroxycyclobut-1-ene.394-395
Perilla aldehyde underwent the Wittig reaction,39s and also reacted with 1methoxy-1-thiophenoxycyclopropaneto give (I 86).397The 5,6-epoxide of carvone
379
3B0
381
383
G. S. R. Subbarao and N. S. Sundar, J. Chem. Res. ( S ) , 1979, 282.

S. G. Levine and B. Gopalkrishnan, Tetrahedron Lett., 1979, 699.
J. W. Suggs, S. D. Cox, R. H. Crabtree, and J. M. Quirk, Tetrahedron Lett., 1981, 22, 303.
Takasago Perfumery Ltd., Jap. P., 2627/1980.
S. D. Sharma, A. S. Sethi, A. L. Bedi, and R. C. Aggarwal, Indian J. Chem., Sect. B., 1980, 19,
811.
G. Accrombessi, P. Geneste, J. L. Olive, and A. A. Pavia, Tetrahedron, 1981, 37, 3135.

A. A. Pavia, P. Geneste, and J. L. Olive, Bull. SOC.Chim. Fr., Part 21, 1981, 24.
385a A. Akhila and D. V. Banthorpe, Indian J. Chem., Sect. B, 1980, 19, 998.
3ae D. Babin, J. D. Fourenon, and M. Julia, Tetrahedron, Suppl. 9, 1981, 37, 1.
3 8 7 G. Mehta and A. V. Reddy, Tetrahedron Lett., 1979, 44, 546.
G. Buchi and H. Wuest, J. Org. Chem., 1979, 2625.
38B J. A. Findlay, D. N. Besai, G. T. Lonergan, and P. S. White, Can. J. Chem., 1980, 58, 2827.
0.P. Vig, M. L. Sharma, A. S. Sethi, and S. D. Sharma, Indian.J. Chem., Sect. B, 1980,19, 176.
3g1 T, Fujisawa, T. Sato, T. Kawara, and K. Ohashu, Tetrahedron Lett., 1981, 22, 4823.
J. Sepiol, J. Mirek, and R. L. Soulen, Pol. J . Chem., 1978, 52, 1389.
393 S. R. Wilson, L. R. Phillips, Y. Pelister, and J. C. Huffman, J. Am. Chem. Soc., 1979,101,7373.
394 M. van Audenhove, D. De Keukeleire, and M. Vandewalle, Bull. SOC.Chim. Belg., 1981, 90,
255.
395 F. Andenaert and M. Vandewalli, Tetrahedron Lett., 1981, 22, 4521.
T. Lok Ho, Synth. Cummun., 1981, 11,605.
3 B 7 T. Cohen and J. R. Matz, Tetrahedron Lett., 1981, 22, 2455.
384
385
40
also underwent a Wittig addition of .CH,CO,R followed by cyclization to (187).39s

CsF in the presence of Si(OR), (R = alkyl) appeared to be an efficient catalyst for
Michael addition to a,p-unsaturated ketones : carvone and pulegone both thus
reacted with a c e t o p h e n ~ n e .Trimethylvinylsilane
~~~
in the presence of TiCl4
similarly transferred its vinyl group to p u l e g ~ n e . ~ ~ ~
3,3,5,5-Tetramethyl-limonene
resulted from the condensation of 1,1,3-trimethylbut-2-en- 1-01 catalysed by H,S0,-pentane,401 and the corresponding 3,5-dimethyl
compound and also 3,5-dimethyl-a-terpineolresulted from treatment of 1,3dimethylbut-2-en- 1-01with T ~ O H - p e n t a n eTetramethylated
.~~~
carvone and carveols
have been prepared by the regio-controlled opening of tetramethyl-limonene
oxide.4031,2-Dihydrocarvone reacted with PhSeCH,CHO followed by MsC1-Et3N
to yield (188).404Such vinylations a to a ketone group should provide ready access
to a variety of substrates useful for the Cope-Claisen reactions and in the synthesis
of natural products. Methods have been developed for the functionalization of
limonene at C-9 with -CH,C02H,405.C(OH) (C0,Et),,406 or S C H = C H C O ~ M ~ , ~ O ~
and also of p-menth-l-ene at C-6 with the last
Carvomenthene was
methylated at C-4 by MeI-KI.408 A hydroxymethyl group was introduced at C-1
of 1,2-dihydrocarvone on treatment with p a r a f ~ r m a l d e h y d e ,and
~ ~ ~the same
substrate reacted with 3,3-dimethylacrylic acid-Et2NLi to yield (1 89).410Acetone
added electrophilically in the presence of BuLi-TMEDA to the endocyclic double
bond of protected carvone to give products with shift of u n ~ a t u r a t i o n . ~ ~ ~
Selected from numerous other, apparently randomly studied, reactions are :
carboxylation of menthol or menth-l-ene at C-1, C-3, C-4, and C-8 on treatment
with CO-BF3-ClCH2C02H,412coupling of limonene at C-2 and C-4 to xylenols
in the presence of Amberlite IR-120 resin,413dimerization (C-3 to C-3 linkage) of
carvone induced by FeC1,,414and the aromatization observed in the BF,-catalysed
reaction of terpinolene and tetrahydrogeraniol to give cymen-8-yl tetrahydrogeranyl
ether.
308
380
400
Ool
Oo2
403
Oo4
Oo5
406
Oo7
H. Orszanska, K. Witkiewicz, and Z. Chabudzinski, Pol. J . Chem., 1980, 54,45.

J. Boyer, R. J. P. Corriu, R. Perz, and C. Reye, J . Chem. Soc. Chem. Commun., 1981, 122.
R. Pardo, J.-P. Zahra, and M. Santelli, Tetrahedron Lett., 1979, 4557.
3. M . R. Hoffmann, and H . Vathke-Ernst, Chem. Ber., 1981, 114, 1182.
H. Vathke-Ernst and H. M. R. Hoffman, Chem. Ber., 1981,114,1548.
R. J. Giguere and H. M. R. Hoffman, Tetrahedron Left., 1981, 22, 5039.
C. J. Kowalski and J. S . Dung, J. Am. Chem. SOC.,1980, 102, 7950.
N. Fukamiya, M. Oki, M. Okano, and T. Aratani, Chem. Znd. (London), 1981, 96.
S. N. Pardo, S. Ghosh, and R. G. Salomon, Tetrahedron Lett., 1981, 22, 1885.
B. B. Snider, D. M. Roush, D. J. Rodini, D. Gonzalez, and D. Spindell, J . Org. Chem., 1980,
45,2773.
408
408
410
41i
412
013
414
(16
Taiyo Perfumery Co. Ltd., Jap. P., 162 712/1980 (Chem. Abstr., 1981, 94, 127 159).
J. A. Findlay, D. N. Desai, and J. B. Macaulay, Can. J . Chem., 1981, 59, 3303.
I. Casinos, R. Mestres, and M. Valero, An. Quim., 1980, 76, 70.
D. Hoppe, R. Hanko, A. Bronneke, and F. Lichtenberg, Ang. Chem. tnt. Ed. Engl, 1981, 20,
1024.
S. D. Pirozhkov, K. V. Puzitskii, T. N. Myshenkova, K. C. Ryabora, and S. S . Poddubnaya,
tzv. Akad. Nauk SSSR, Ser. Khim., 1979, 841.
E. Pother, Bull. SOC.Chim. Fr., Part I t 1981, 335.
R. H. Frazier and R. L. Harlow, J . Org. Chem., 1980, 45, 5408.
K. Nagai and M. Nakayama, Bull. Chem. SOC.J., 1981,54, 3607.
Monoterpenoids
41
General Reactions.-( -)-Limonene racemized on pyrolysis and formed a variety

of compounds. Thus (190) gave (191)-(193).4161417 It also cyclized to chiral aterpineol on treatment with chloroacetic acid and a cationic resin4lSor isomerized
and polymerized on heating with P205.419Terpinolene and acetylosulphoacetic
acid gave a-fenchyl acetate (I 1 %) in addition to expected acetates with the menthane
Isolimonene (p-mentha-2,8-diene) isomerized to p-mentha-2,4(8)and the 7-sulphito-derivative of p-menth- 1-ene could be pyrolysed
diene with Na,421
to p-phellandrene (89 %).422 (-)-Menthone on treatment with NBS and quinoline
followed by the Shapiro procedure gave p-mentha-2,4-diene :the same paper reports
a five-step synthesis of a-phellandrene from ethyl 4-methylpentan-2-en-0ate.~~~
(192)
(193)
Products of addition of IF424and of N-chlorosulphonamides425
to p-menth-1-ene,
of Br, to y - t e ~ i n e n e of
, ~ ~NOCl
~
to ~-menth-3-ene,~~'
and of hydration of at e r p i n e 0 1 have
~ ~ ~ been characterized. An interesting example of remote and selective
GH GBUn3
i, NaH-CS,-Me1
m-CIC,H,CO,H
ii, Bun,SnH
(194)
(195)
S. G . Traynor, K. J. Crowley, and W. Cocker, J . Chem. Res. (S), 1981, 175.

417 K. J. Crowley and S. G . Traynor, Tetrahedron, 1978, 34, 2783.
Y . Matsubura, K. Tanaka, M. Urata, T. Fukungaga, M. Kuwata, and K. Takahoshi, Bull.
Chem. Soc. J., 1979,52, 1757.
A. I. Lamatkin, Y . P. Klynev, and A. G . Gordon, Khim. Khim. Tekhnol. (Minsk). 1980,15,
112.
420 R. Luft, J . Org. Chem., 1979, 44, 523.
4B1 A. N. Misra, M. R. Sarma, R. Soman, and S. Dev, Indian P, I46086/1976 (Chem. Abstr.,
1980,93, 235 705).
a2 L. M. Hirschy, B. J. Kane, and S. G. Traynor, U.S. P., 4 136 126/1979.
483 L. A. Paquette and R. F. Doehner, J . Org. Chem., 1980, 45, 5105.
424 S. Rozen and M. Brand, Tetrahedron Lett., 1980, 21,4543.
laSZ . Rykowski and J. Wrzesien, Pol. J. Chem., 1981, 55, 371.
426 R. M. Carman, and J. K. L. Maynard, A m . J . Chem., 1981, 32, 217.
ta7 V. Sadasivan and J. Verghese, Indian J. Chem., Sect. B, 1979, 17, 546,
428 P. C. Mathew and J. Verghese, Indian J. Chem., Sect. B., 1979, 17, 172.
416
42
electrophilic fluorination at a C-H bond has been discovered: reaction of F, and

menthyl p-nitrobenzoate gave substitution at C-8 (and, on forcing, at C-1).
Treatment of the former product with BF3 etherate yielded the ester of isopulegeo1.429 It is rare for a non-radical process involving fluorine to proceed in
reasonable yield and with high selectivity.
A new method for 1,3-transposition of OH of allylic alcohols via stannanes has
been developed, e.g. (194)4( 195).430This procedure is especially valuable for the
preparation of alcohols with the thermodynamically less stable exo-double bond.
The hydrolysis of a-terpinyl chloride to a - t e r p i n e ~ lthe
, ~ ~formation
~
of dimenthylphosphorous chloride from
the cyclization of 8-aminomenthanes via
iminium intermediates to give 1-aza-adamantane derivatives,433and the [3,3]sigmatropic rearrangement of the lactone derived from hydration of menth- 1-en-9-oic
have been reported. Substitution of 6-substituted carveyl diethylphosphates
with organoaluminium compounds (Me,AlX; X = OPh, SPh, or NHPh) proceeded
with predominant inversion, but with R3Al (R = alkyl) dimerization occurred.435
The product distribution and the high P-deuterium isotope effect (kH/kD= 2.5)
indicated that the S,1 solvolysis of neomenthyl tosylate proceeds via ratelimiting sluft of hydride ion followed by elimination.436The presumed syn-elimination of the di-isopropylaluminium derivative of menthol required a lower temperature than decomposition of the acetate or xanthate, and gave better yields,
although there was some i s ~ m e r i z a t i o n This
. ~ ~ ~paper gives an excellent list of
references to elimination reactions of menthol and its derivatives. 8,9-Dihydroxylimonene yielded p-menth-l-ene-l O-al (a component of Bulgarian rose oil) on
treatment with KHSOl or SOCI,, but oxalic acid gave I O-hydroxylirn~nene.~~~
Menthone was elegantly transposed into carvomenthone by the sequence
(196)+( 197).439Piperitol was isomerized into isomenthone over cobalt catalysts.uo
Piperitone, p-menth-3-en-2-oneY and 8,9-dihydrocarvone can by pyrolysed to
aromatics that have lost the Pr' group in fair yields (30-50%),441 and menthone
can be converted into piperitone and other p-menthen-3-ones via bromination and
Zn treatment.442Pulegone on reaction with HOCl formed 4-chloro-p-menth-8-en3 - 0 n e , ~and
~ ~ O-acetylated dienolates of pulegone have been prepared.444Carvomenthene oxide was isomerized to p-menth- 1(7)-en-2-01, carvotanacetol, and
cyclopentane derivatives over solid acids and bases,445and 6-thiophenoxy-8,9p28
430
p31
S. Rozen, C. Gal, and Y. Faust, J . Am. Chem. SOC.,1980, 102, 6860.

Y. Ueno, H. Sano, and M. Okawara, Synthesis, 1980, 1011.
S. Anandaraman, K. N. Gurudutt, C. P. Natarajan, and B. Ravindranath, Tetrahedron Lett.,
1980, 21,2189.
433
433
434
435
436
p37
438
438
440
441
442
443
p44
445
H. W. Krause and A. Kinting, J . Prakt. Chem., 1980, 322, 85.

A. Pancrazi, 1. Kabore, B. Delpech, and Q. Khuong-Huu, Tetrahedron Lett., 1979, 3729.
G. Frater, Helv. Chim. Acta, 1979, 62, 641.
A. Itoh, S . Ozawa, K. Oshima, S. Sasaki, H. Yamamoto, T. Hiyama, and H. Nozaki, Bull.
Chem. Soc. J . , 1980,53,2357.
S. Hirsl-Starcevic,Z . Majerski, and D . E. Sunko, J . Org. Chem., 1980, 45, 3388.
E. Brieger, S. W. Watson, D. G. Barar, and A. L. Schene, J . Org. Chem., 1979,44, 1340.
M. Nomura, Y . Fujihara, and Y. Matsubara, Nippon Kagaku Kaishi, 1979, 305.
W. E. Fristad, T. R. Bailey, and L. A. Paquette, J . Org. Chem., 1980, 45, 3028.
H. Kumobayashi, H. Taketomi, and S. Akutogawa, Jap. P., 2628/1980.
G. L. Lange, V. A. Pereira, and M. Weedle, Can. J . Chem., 1980, 58, 1639.
C. Metge and C. Bertrand, C . R . Hebd. Seances Acad. Sci., Ser. C , 1980, 291, 255.
S. G. Hegde and J. Wolinsky, Tetrahedron Lett., 1981, 22, 5019.
R. Pardo and M. Santelli, Tetrahedron Lett., 1981, 22, 3843.
K. Arata, S. Akutagawa, and K. Tanabe, Bull. Chem. SOC.J., 1978, 51, 2289.
Monoterpenoids
43
(1 96)
(1 97)
dihydrocarvonehas been reported.44sPhotochemicallyinduced addition of allene to
piperitone gave (198), which underwent acid-catalysed rearrangement to (199).447
Irradiation of terpinen-4-01 in the presence of HgO-Iz gave 2-iodo-l,4-cineole
which could be reduced to 1,4-cineole (79 %).448 Iodometric assay of ascaridole gave
15 products, some iodinated, some derivatives of 1 , 4 - t e r ~ i nLimonene
.~~~
reacted
with 'PhSeOH' to give a product which after removal of selenium (Bu",SnH)

yielded 1 , 8 - ~ i n e o l eBamford-Stevens
.~~~
reaction of the tosylhydrazone of 2-keto1,8-cineole yielded cyclopentane derivatives and dimers derived from carbenoid
intermediate^.^^^ Pinol [the 6,8-cineole derivative (200)] reacted with NBS to form
2,6-dibromo-1 , 8 - ~ i n e o l e or
, ~ ~could
~
be oxidized with Hg" salts to 4a-hydroxyp i n 0 1 . ~Hydroboration
~~
of (201), followed by conversion into the N-oxide and Cope
elimination, gave the unusual compound (202).454
Studies using 2H-labellinghave indicated that allylic alkylation of carveyl acetate
catalysed by PdO complexes involve a symmetrical x-ally1 intermediate;455 this
refutes a previous mechanism.456
The chirality of (203) was establishedby conversion
OMe
(203)
P. Bakuzis and M. L. F. Bakuzis, J . Org. Chem., 1981, 46, 235.
D. K. M. Duc, M. Fetizon, I. Hanna, A. Olesker, C. Pascard, and T. Prange, J . Chem. SOC.,
Chem. Commun., 1980, 1209.
u* H. Takahashi and M. Ito, Chem. Lett., 1979, 373.
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~0 R. M. Scarborough, A. B. Smith, W. E. Barnette, and K. C. Nicolaou, J . Org. Chem., 1979,44,
44a
1742.
461
46a
458
464
F. Bondavalli, A. Ranise, P. Schenone, and S. Lanteri, J . Chem. SOC.,Perkin Trans. I , 1979,885.

D. Mrozinska, A. Siemienink, K. Piatkowski, and H. Kuczynski, Pol. J. Chem., 1979,53,2213.
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2626.
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u6J. C. Fiaud and J. L. Malleron, Tetrahedron Lett., 1981, 22, 1399.
466
44
into chiral a - p h e l l a n d ~ e n e Chiral

. ~ ~ ~ terpenes have been used in several studies as
adjuvants for asymmetric synthesis. The x-allyltitanium complex (204) (R = H or
Me) reacted with CO, under mild conditions to form a C-C bond (205; 18%
enantiomeric excess, e.e.) : this provides the first example of asymmetric fixation of
C02.458A phosphorus-containing cationic rhodium complex incorporating
( -)-a-phellandrene catalysed asymmetric reductions (95 % e.e.),459and asymmetrical co-ordination of prochiral dienes to form chiral Fe(CO), complexes has
been achieved (25 % e.e.) by direct transfer of the Fe(CO), group from its complex
with ( +)-~ulegone.~~O
Metallation and alkylation (MeI) of aldimines derived from
various chiral terpene methoxyamines (e.g. 1-methoxy-2-amino-p-menthane) and
octanal produced, after hydrolysis, ( +)-2-methyloctanal (1 1-75 % e.e.).461
(-)-Menthol
could be converted into (+)-(neoisomenthylsulphony1)methyl
isocyanide, which reacted with 1,3-dibromobutane to give, in two steps, the enantiomers of 2-methylcyclobutanone.462(This reaction is well known for RCH,NC,
where R = Tos etc.) The conformationally locked adjuvant (206) has been prepared
from ( + ) - ~ u l e g o n e ~
and
~ , used in a synthesis of ( -)-mevalonolactone.464
1
7 The Camphane Class

See also reference 120.
Occurrence; Synthesis of the Skeleton.-Bornyl

chloride has been identified
(g.c.-m.s.) in Thymus spp.: it was considered an artifact of a - ~ i n e n ebut
~ ~the
~
origin of the required HCl was not explained. Campholenic aldehyde and exo-6hydroxy-2,3-dimethylnorborn-2-ene
occur in Cistus and Abies spp. re~pectively.~66*467
Treatment of 1,3-dibromo-3,7-dimethylocta-6-en-2-one
with [Fe,(CO),] gave
camphor (38 %).468 Acid treatment of the phenylhydrazone of campholenic
aldehyde gave 2,f~dinitrogen-bridged~ a m p h a n eDiels-Alder
.~~~
coupling of cyclopentadiene with acetylenic esters led to esters of n ~ r b o r n e n e . ~ ~ ~
A. J. Birch, W. D. Raverty, and G. R. Stephenson, J . Chem. SOC.,Chem. Commun., 1980,857.
F. Sato, S. Iijima, and M. Sato,J. Chem. SOC.,Chem. Commun., 1981, 180.
45B M. Lauer, 0. Samuel, and H. B. Kagan, J . Organometal. Chem., 1979, 177, 309.
460 A. J. Birch, W. D. Raverty, and G. R. Stephenson, Tetrahedron Lett., 1980,21,197.
u1 A. I. Meyers, Z. Brich, E. W. Erickson, and S. G. Traynor, J . Chem. SOC.,Chem. Commun.,
1979, 566.
462 D. van Leusen, P. H. F. M. Rouwette, and A. M. van Leusen, J . Org. Chem., 1981,46, 5159.
463 E. L. Eliel and J . E. Lynch, Tetrahedron Lett., 1981, 22, 2855.
464 E. L. Eliel and K. Soai, Tetrahedron Lett., 1981, 22, 2859.
465 V. P. Papagorgiou and N . Argyriadou, Phytochemistry, 1981, 20, 2295.
466 P. Proksch, P. G . Guelz, and H. Budziekiewicz, 2. Nuturforsch., Tie1 C , 1980, 35, 529.
467 A. Koedam, J. C. Scheffer, and A. B. Svendsen, J . Agric. Food Chem., 1980,29,862.
R, Noyori and seven others, J . Am. Chem. SOC.,1979, 101,221.
IeS
B. Fouchet, M. Joucla, and J. Hamelin, Tetrahedron Lett., 1981, 22, 1333.
4 7 0 F. M. Simmross and P. Wegerstahl, Liebigs Ann. Chem., 1981, 1089.
457
458
45
Mono t erpenoids
Oxidation-Reduction.-Chemical oxidation (Cr0,-HOAc) of (-)-bornyl acetate

yielded a mixture of 3-, 5-, and 6-oxobornyl acetates whereas microbiological
oxidation (Helminthosporum spp.) gave the 5-0x0- and the 2,5- and 2,6-dioxoderivatives. The latter type of oxidation of ( +)-bornyl acetate occurred exclusively
at (2-5. Fusarium spp. hydroxylated both substrates at C-5, but now without
concomitant cleavage of acetate.47f Bornylmagnesium bromide with MOO,pyridine-HMPA gave borneol with retention of configuration. If general, this
method should be important for the stereoselective conversion of bromides into
Ozonolysis of camphor in the presence of vinyl acetate gave camphor
lactones.473e474
10-Chlorocamphor-10-sulphme (easily prepared from (-)-camphor10-sulphonyl chloride) was ozonized to the 10-oxychloro-derivative,which is useful
for the optical resolution of
Camphor and camphor-3-carboxylic acid
were reduced with NaBH, or NH,-BH, to different proportions of exo- and endoproduct^.^^^,^^^ The enantiomeric camphorquinones have been stereoselectively
reduced by chiral models for NAD(P)H.478Camphor was reductively aminated by
f o ~ m a r n i d e .The
~ ~ ~exo-ester of 3-bromocamphor-3-carboxylic acid was both
debrominated and decarboxylated by strong bases: NaBH, in MeOH gave
debromination only, whereas in diglyme decarboxylation
General Reactions.-The potassium salts of cis- and trans-pinane-2-01s in DMSO
or in the pinanols as solvent were more effective dehydrohalogenating agents for
bornyl chloride or 2,6-dichlorocamphane than was KOBu' in DMS0.481Treatment
of 3-bromocamphor with N-methylaniline yielded camphene, tricyclene, and
b ~ r n y l a n i l i n e ,and
~ ~ ~with lithium hexamethyldisilazide-LiBuf gave the novel
a-ketodianion equivalent (207), which on quenching with ,H20 yielded [3,3-,H,]camphor.483The rates of base-catalysed ,H-exchange of thiocamphor were 23- and
12-fold greater (exo and endo) than those for camphor. The reasons for the rate
enhancements are fully
Thiocamphor reacted in sequence with Na,
& fi
&i
OLi
(207)
471
Li
(208)
(209)
M. S. Allen, N. Darby, P. Salisbury, E. R. Sigurdson, and T. Money, Can.J . Chem., 1979,57,

733.
47z
478
474
476
476
477
478
479
480
481
482
,1133
N. J. Lewis and S. Y. Gabhe, Aust, J . Chem., 1978, 31, 2091.

R. Lapalme, H. J. Borschberg, P. Soucy, and P. Deslongchamps, Can.J . Chem., 1979,57,3272.
R. Barba, A. Guirado, M. L. Segura, and A. Soler, An. Quim., 1979, 75, 967.
M. F. Haslanger and J. Heikes, Synthesis, 1981, 801.
G. C. Andrews and T. C. Crawford, Tetrahedron Lett., 1980, 21, 693.
R. Antkowiak, Bull. Acad. Pol. Sci., Ser. Sci. Chim., 1979, 27, 103.
A. Ohno, T. Goto, J. Nakai, and S. Oka, Bull. Chem. SOC.J., 1981, 54, 3478.
I. I. Bardyshev and N. G. Kozlov, Dokl. Akad. Nauk SSSR, 1979,23,630.
R. Antkowiak and W. Antkowiak, Bull. Acad. Pol. Sci., Ser. Sci. Chim., 1978, 26, 933.
S. G. Traynor, B. J. Kane, J. B. Coleman, and C. G. Cardenas, J . Urg. Chem., 1980,45,900.
A. G. Giumanini and M. M. Musiani, J. Prakt. Chem., 1980, 322,423.
C. J. Kowalski, M. L. O'Dowd, M. C. Burke, and K. W. Fields, J . Am. Chem. SOC.,1980,102,
5411.
484
N. H. Werstiuk, H. Nick, and P. Andreis, Can. J . Chem., 1978, 56, 2605.
46
[Fe(CO),] and acid chloride to give 2-thioesters of b ~ r n e n e Transposition

.~~~
of
camphor into its 3-oxo-isomer via hydroboration of the eneamine, oxidation, and
elimination,486decarbonylation of camphor in glow
its metallation at
C-3,488the products of its Beckmann rearrangement,4sgpreparation of bornylamines
from bornyl chloride.490and mercuration of b ~ r n e n e have
~ ~ l also been reported.
Camphor tri-isopropylbenzenesulphonylhydrazonereacted with lithium alkyls
and BunI to yield the vinylcarbanion equivalent (208) which can be quenched
with a variety of electrophiles (e.g. Br+, Bu+, Me2C0).492Aryl vinyl selenoxides
and the lithium enolate of camphor gave the spiro-cyclopropyl derivative at
C-3.493 (-)-endo-Bornyl-l,2,4-triazolinedionewas used as a dieneophile in cycloaddition to cyclo-octatetraene (the first step of the resolution of the latter).4w
Bornyl-A3-1,3,4-oxadiazolin-2-ones(epimers at C-1) decomposed concertedly
to give either diazocamphane or camphor.495 Bornyl- 1 , 2 - d i a z e n e ~and
~~~~~~~
-tria~enes4~8
have been prepared. The endo-configuration at C-6 in a 6,8-dibromocamphor has been proved by bridging of C-6 to C-8 with a -(NW2- linkage.499
Ring-opening of the camphane skeleton to give derivatives of camphoric acid or
1,2,2,3-tetramethylcyclopentaneresulted from camphor ( +HN03),50010-sulphitocamphor ( + KOH),501camphonic anhydride ( + RNH2),502and N-nitrobornylimine ( +A);503 derivatives of 1,1,2,2-tetrarnethylcyclopentane (i.e. via methyl
migration) resulted from photolysis of c a m p h o r q ~ i n o n e3,3-Dibromocamphor
.~~~
( +AgNO,) gave 4-bromo-l,2,2-trimethylcyclohex-3-enecarboxylic
acid and its
3-bromo-isomer : the former could be cyclized (H2S04)to (209).505
Tricyclen-lO-oic acid was oxidized (KMnO,) to the 3-ketone, which was cleaved
to S-bromocamphan-2-one- 10-oic acid;506the tosylhydrazone of tricyclen-3-one
(and also of isotricyclen-Zone) underwent Bamford-Stevens decomposition in
ROH solvent to the 3- or 2-OR
8-bromotricyclene was coupled
(RLi) with isoprene oxide to give a sesquiterpene
endo-3-AminoH. Alper, B. Marchand, and M. Tanaka, Can. J . Chem., 1979, 57, 598.
F. Bondavalli, P. Schenone, and A. Ramise, J . Chem. Res ( S ) , 1980, 257.
4 8 7 G. Kruppa and H. Suhr, Liebigs Ann. Chem., 1980, 677.
4 8 8 0. A. Kruglaya, L. I. Belousova, D. V. Gendin, I. D. Kalikhman, and N. S. Vyazankin,
J . Organometal. Chem., 1980, 201, 69.
489 G. R. Krow and A . Szczepanski, Tetrahedron Lett., 1980, 21,4593.
490 M. E. Spiridonova, 0. I. Korobkova, L. A. Tilchourova, and G . I. Sterligova, Khim. Prir.
Soedin., 1981, 673.
491 E. V. Skorobogatova, L. N. Povelikina, and V. R. Kartashov,Zh. Org. Khim., 1980,16,2318.
482 F. T. Bond and R. A. Dipietro, J . Org. Chem., 1981, 46, 1316.
M. Shimizu and I. Kuwajima, J . Org. Chem., 1980, 45, 2921.
a4J. M. Gardlik and L. A. Paquette, Tetrahedron Lett., 1979, 3597.
495 A. J. Paine and J. Warkentin, Can. J . Chem., 1979, 57, 2681.
496 M. J. Kulshreshtha and N. M. Khanna, Indian J . Chem., Sect. B, 1979, 18, 90.
4 8 7 W. E. Hahn and E. Kozlowskagramsz, Pol. J . Chem., 1979, 53, 1729.
4 9 8 S. Treppendahl and P. Jakobsen, Acta Chem. Scand., Ser. B, 1980, 34, 303.
S. Nagai, N. Oda, and I. Ito, Heterocycles, 1979, 12, 1275.
I. Kitagawa and seven others, Chem. Pharm. Bull., 1981, 29, 2540.
601 H. J. Liu and W. H. Chan, Can. J . Chem., 1979, 57, 708.
K. H. Bell, Aust. J . Chem., 1981, 34, 665.
603 G. Buchi and H. Wuest, J . Org. Chem., 1979, 44,4116.
604 M. B. Rubin and A. Gutman, 7th IUPAC Symposium on Photochemistry, 1978, p. 287.
R. M. Carman and R. Fielden, Aust. J . Chem., 1979, 32, 2331.
L. Borowiecki, B. Makowski, and W. Wodzki, Pol. J. Chem., 1979, 53, 2267.
L. Borowiecki and M. Welniak, Pol. J . Chem., 1978, 52, 2173.
'Oa
M. Tamura and G . Suzukamo, Tetrahedron Lett., 1981, 22, 577.
486
486
Mono terpenoids
47
(212)
(213)
camphor on deamination gave isotricyclen-Zone(13 %) :509 opening of the C, ring
of the latter gave bicyclo[2.2.1lheptane d e r i v a t i ~ e s .Fenchocamphorone
~~~*~~~
(210)
was oxidized (Se0,) to the quinone and functionalized (CH2N2; Pd-H,) to
(21 l).512Carvonecamphor (212) gave (hv, MeOH; Br,; A) the isomers of (213). The
epimer of the initial product (exo-Me) resulted from cleavage of the C4 ring to a
biradical which r e c y c l i ~ e d . ~ ~ ~
8 The Isocamphane Class
New routes to camphenilone and dehydrocamphene derivatives using alkenes514

or allenic esters as dienophiles in Diels-Alder reactions515have been developed.
Lewis acid-catalysed coupling of a$-unsaturated methyl ketones with cyclopentadiene favoured exo-products except when TiCl, was used,51g and led to
isocamphanes that were s p a s m ~ l y t i c s The
. ~ ~ ~tricyclene (2 14) could be converted
(214)
(2 15)
(2 16)
into 5-iodocamphene and 5,6-dihydrocamphene, and so provides a route to otherwise inaccessible homoallylic functionalizations of c a m ~ h e n e . (-)-Camphene
~l~
resulted from syn-elimination of derivatives of ( +)-isocamphenilanic a~id.51~~5~0
The absolute configuration of the acid was established by X-ray analysis.52o
This confirms the previously deduced stereochemistry of (-)-camphene as (1S,4R)
but is in conflict with an earlier report of the conversion of (-)-camphene into the
(-)-acid.
An efficient route to 7-oxocamphene involved as its key step the solvolytic
rearrangement of 3,3-ethylenedioxyisobornyl tosylate (derived from camphorq ~ i n o n e )Brief
. ~ ~ (3
~ min; 0 "C) treatment (PCl,-CaCO,) of borneol gave excellent
yields of camphene hydrochloride: longer reaction times gave bornyl
0.E. Edwards, J. Dixon, J. W. Elder, J. R. Kolt, and M. Lesage, Can.J. Chem., 198 1,59,2096.
A. Garcia-Martinez and A. Garcia-Fraile, An. Quim., 1980, 76, 127.
m A. Garcia-Martinezand A. Garcia-Fraile, An. Quim., 1980, 76, 327.
612 R.F. Childs and C. V. Rogerson, J . Am. Chem. SOC.,1980, 102,4159.
T. Gibson, J. Org. Chem., 1981, 46, 1073.
614 E. Dworan and G. Buchbauer, Chem. Ber., 1981, 114, 2357.
2.M. Ismail and H. M. R. Hoffmann, J. Org. Chem., 1981,46, 3549.
616 J. Bachner, U. Huber, and G. Buchbauer, Monatsh. Chem., 1981,112,3517.
617 G. Buchbauer, W. Pernold, D. Rassl, and B. Black, Monatsh. Chem., 1981, 112, 517.
618 S. N. Sunyawanshi and U. R.Nayak, Tetrahedron Lett., 1979, 269.
a8 G. W. Hana and H. Koch, Chem. Ber., 1978,111,2527.
I B 0J. M. Midgley and six others, J. Chem. Soc., Perkin Trans. I , 1978, 1312.
621 D. G. Patil, H. P. S. Chawla, and S . Dev, Tetrahedron, 1979, 35, 527.
OZ8 R. W. Carman and I. M. Shaw, Aust. J. Chem., 1980, 33, 1631.
510
48
Camphene could be hydroaluminated and oxidized to endo- and e ~ o - l O - o l sand

,~~~
(-)-camphor was converted (eight and nine steps respectively) into (-)-5,6dihydroxycamphene and 1,4-diformyl-2,3,3-trirnethylcyclopentene,
the latter for
testing as a p h y t ~ h o r m o n e . ~ ~ ~
Camphene condensed with methyl propiolate under the influence of Lewis acids
to give spiro-cyclobutene derivatives525and with PC1,Me-AlCl, to form C-3-C-8
bridged phosphorus a d d u ~ t s Isocamphan.~~~
10-a1 condensed with rhodanine to
yield a fungicidal
Camphenyl-lithium can readily be converted into the
tetra-alkyl-chromium or -uranium
Nojigiku alcohol (2 I5), previously synthesized from camphene or tricyclene, has
been prepared from (-)-isobornyl acetate by remote oxidation (cf. ref. 471) and
functionalization (seven steps) : this confirms the absolute configuration of the
natural
Camphenilone and camphene oxide were starting materials for
the synthesis of albene (a C12 c o m p o ~ n d )and
~ ~(~+)-@-santalol
?~~~
(C4532respectively. The norcamphene (2 16) with PdCl, yielded a bis-n-allyldichloro-di-Pd
complex that could be methylated (CdMe,; MeMgI) at C-3 to give exo-isosantene
(90 %), which is otherwise difficult to
9 The Pinane Class

See also references 30 and 31 (structure) and 62 (stereochemistry).
Occurrence.-Myrtenol was the main component of the oil of a Chrysanthemum
spp. ;534 Filipendulol (7-hydroxy-a-pinene) occurred in Achillea spp.,535W3 4Shydroxychrysanthemyl acetate and 3s-hydroxyisochrysanthemyl acetate in Diotis
~ p p . , and
~ ~ 'benzoyloxypaeoniflorin (217 ; G = 6-benzoyl-@-glucose;Bz = benzoyl)
and the related paeoniflorigenone in roots of Paconia and Paeoniae spp,53S,539
Rearrangement, Oxidation, Reduction, Simple Functiona1izations.-( +)-a-Pinene
was converted into the rare (+)-P-pinene (optical yield 90%) via conversion into
A. V. Kuchin, L. I. Akhmetov, V. P. Yurev, and G. A. Tolstikov,Zh. Obschch. Khim., 1979,49,
401.
524 M. S. Allen, N. Lamb, T. Money, and P. Salisbury, J. Chem. SOC.,Chem. Commun., 1979, 112.
625 B. B. Snider, D . J. Rodini, R. S. E. Conn, and S. Sealfon, J. Am. Chem. SOC.,1979,101,5283.
526 E. Vilkas, M. Vilkas, J. Sainton, B. Meunier, and C. Pascard, J. Chem. SOC.,
Perkin Trans. 1,
1980, 2136.
527 G. Buchbauer and M. Kern, Arch. Pharm. (Weinheim, Cer.), 1980, 315, 1043.
5 2 8 A. N. Nesmeyanov, I. V. Shchirina-Eingoru, G. M. Khvostik, V. N. Sokoloy, and I. I. Kritskaya', Izv. Akad. Nauk SSSR, Ser. Khim., 1979, 2826.
528 N. Darby, N. Lamb, and T. Money, Can. J. Chem., 1979, 57, 742.
6ao W. Kreiser, L. Janitschke, W. Voss, L. Ernst, and W. S. Sheldrick, Chem. Ber., 1979,112,397.
531 W. Kreiser and L. Janitschke, Chem. Ber., 1979, 112, 408.
532 P. A. Christenson and B. J. Willis, J. Org. Chem., 1979, 44, 2012.
533 Y. Castanet and F. Petit, Tetrahedron Lett., 1979, 3221.
534 Y. Uchio, K. Tomosue, N. Nakayama, A. Yamamura, and T. Waki, Phytochemistry, 1981,20,
2691.
535 A. D . Dembitski, R. A. Yurina, A. E. Lyuts, and M. I. Goryaev, Khim. Prid. Soedin., 1979, 862.
536 A. D. Dembitski, R. A. Yurina, and M. I. Goryaev, Izv. Akad. Nauk Kaz. SSR, Ser. Khim.
1980, 55.
537 J. D e Pascual Teresa, A. F. Barrero, E. Caballero, and M. Medarde, An. Quim., 1979,75,323.
538 I. Kitagawa, M. Yoshikawa, K. Tsunaga, and T. Tani, Shoyakugaku Zasshi, 1979, 33, 171
(Chem. Abstr., 1980, 92, 169 115).
63B M. Shimizu and eight others, Tetrahedron Lett., 1981, 22, 3069.
523
Monoterpenoids
49
myrtenyl diethylphosphonate followed by reduction (LiA1H4).540Catalysts have

been evaluated for the isomerization of ~ t - p i n e n e and
,~~~
its conversion into camphene was increased 100-fold by the addition of TiO, to the usual optimum
catalysts.642p-Pinene was converted in low yield into the a-isomer in the presence of
Mg0,643and this isomerization, catalysed by NaH-[2H,]DMS0, involved relatively
fast uptake of one atom of tracer transferred from the face trans to the gemdimethyl bridge (owing to steric hindrance) ;544 cis and trans-6-Pinenes resulted from
acid-treatment of ( +)-4-trimethyl~tannylpinane.~~~
,*.
CD,
b b
\
Photo-oxygenation of a-pinene in MeCN-H,O differed from that in aprotic

media: the main hydroperoxide was the same but it was accompanied by (218).64s
Similar reaction of the P-isomer in the presence of metal oxides gave myrtenol,
myrtenal, nopinone, and p i n o c a r ~ o n e .a-Pinene
~~~
was reduced to cis-pinane
(96 % stereoselective) over R u ,and
~ ~electrochemical
~
reduction of 2,4-dibromopinocamphone gave a variety of products devoid of Br.549Hydroboration of aminoand a z i d o - p i n a n e ~and
~ ~ ~the conversion of a-pinene into 2-hydroxy-3-amino- and
3-hydroxy-5-amino-pinaneshave been r e p ~ r t e d . ~ syn-Addition
~ l - - ~ ~ ~ of 2HCl to the
640
641
643
b43
644
645
640
647
648
64a
660
661
66*
663
L. M. Hanvood and M. Julia, Synthesis, 1980, 456.

S. Battalova, T. R. Mukitanova, and N. D. Pak, Dokl. Akad. Nauk SSSR, 1978,242,111.
A. A. Popov and V. A. Vyrdov, Lesokhim. Pohochka, 1978, 2, 6 (Chem. Abstr., 1978, 89,
90 223).
H. Hattori, K. Tanabe, K. Hayano, H. Shirahama, and T. Matsumato, Chem. Lett., 1979, 133.
R. Ohnishi, J . Chem. SOC.,Perkin Trans. 2, 1980, 530.
A. N. Kashin, V. N. Bakunin, I. P. Beletskaya, and 0. A. Reutov, Izv. Akad. Nauk SSSR, Ser.
Khim., 1981, 1180.
P. Capdevielle and M. Maumy, Tetrahedron Lett., 1980, 21, 2417.
M. A. Fox and C. C. Chen, J . Am. Chem. SOC.,1981, 103,6757.
M. S. Pavlin, U.S. P., 4 310 714/1980.
A. J. Fry and G. S. Ginsburg, J . Am. Chem. SOC.,1979, 101, 3927.
I. Uzarewicz and A. Uzarewicz, Pol. J . Chem., 1978, 52, 1907.
K. Burak and Z . Chadbudzinski, Poi. J. Chem., 1978, 52, 1721.
Z. Rykowski and J. Wrzesien, Pol. J . Chem., 1981, 55, 371.
K. Burak and Z . Chadbudzinski, Pol. J. Chem., 1981,55,387.
50
less hindered side of a-and p-pinenes was demonstrated by a combination of 13Cand

lH n.m.r : the resulting tertiary chloride was configurationally pure and isomerized
solely to bornyl chloride. The rapidity of the isomerization with the probable conversion of a tertiary into a secondary carbocation was rationalized by calculations of
strains:554in contrast, acetolysis of cc-pinene appeared to involve approach of H+
from both exo- and endo-sides, with the participation of a bridged intermediate in the
addition
The ArSeCl-catalysedreaction of a-pinene with N-chlorosuccinimide
OsO, in the presence of trimethylwas anomalous and led to pinocarveyl
amine N-oxide-pyridine effectively hydroxylated the hindered double bond in
10-substituted a - p i n e n e ~ .Surprisingly,
~~~
pinan-2-01 could only be efficiently
converted into a-pinene with SOC1,-pyridine : use of POC1,-pyridine and other
conventional methods led to rearrangement.lS0 Potassium cis- or trans-pinan-2oxides are the most basic alkoxides known558and effectively promoted the ringopening of trans-pinene oxide to trans-pinocarveol and trans-pin-3-en-2-01.~~~
The cyclic ether (219) was converted into (220), which underwent rearrangement
to (221) in a manner analogous to the celebrated norcaradiene ring-walk: stereochemical analysis of the rearrangement indicated predominant inversion of
configuration for both the photolytic and thermal processes and so symmetry
considerations of the Woodward-Hoffman type may not be relevant to these (or at
least the thermal) processes.559Esters of pinocarveol were converted into myrtenyl
compounds by C U O A C . ~cis~ * and trans-Verbenyl and verbanyl acetates,661@2
related
and 2-methylverban0ne~~~
have been synthesized for evaluation as attractants for cockroaches.
Ring-opening.-=- and p-Pinenes with various metal salts or acids were converted
into carvey1565~566
or ~ r - t e r p i n y l compounds.
~ ~ ~ - ~ ~ ~ p-Pinene with Pb(OAc), gave 2-,
7-, and 8-acetylated p-menthenes and d i e n e and
~ ~ on
~ ~treatment with HSiC13 and
Ni catalyst formed the 7- and 10-trichlorosilyl derivatives of p-menth-1 -ene(77 %)
and endo-isocamphane respectively.570a-Pinene was converted into 2,2-dimethyl3-cis-(2-methylpropenyl)cyclobutane-l-carboxylicacid and its t r ~ n s - i s o m e r ~ ~ ~
(analogues of the chrysanthemic acids), and a similar ring fission and derivatization
led to (222).572Pinenes could be thermally isomerized over Na or K salts to myrcene
664
666
666
667
668
66B
680
Oel
662
683
664
565
667
66s
c70
671
E. F. Weigand and H. J. Schneider, Chem. Ber., 1979, 112, 3031.

R. Muneyuki, Y. Yoshimura, and K. Tori, Chem. Lett., 1979, 49.
T. Hori and K. B. Sharpless, J . Org. Chem., 1979,44,4208.
R . Ray and D. S. Matteson, Tetrahedron Lett., 1980, 21,449.
B. J. Kane, G . Marcelin, and S. G. Traynor, J . Org. Chem., 1980, 45, 895.
W. T. Borden, J. G. Lee, and S. D. Young, J . Am. Chem. SOC.,1980, 102,4841.
H. Miyawaki, Jap. P., 59 25311979.
C. Nishino and H. Takayanagi, Comp. Biochem. Physiol., 1981,70A, 229.
H. Takayamagi and C. Nishino, J. Chem. SOC.J., Chem. Ind. Chem., 1981, 629.
C. Nishino and H. Takayamogi, Agric. Biol. Chem., 1979, 43, 1967.
Mitsubishi Chem. Industries Co. Ltd., Jap. P., 30 940/1981 (Chem. Abstr., 1981, 94, 150 956).
U. Lipnicka, A. Rykowski, J. Wrzesien, and Z. Z . Chabudzinski, Pol. J. Chem., 1980,54,2373.
A. V. Pol, V. G. Naik, and H. R. Sonawane, Indian J . Chem., 1980, 19, 603.
A. Watanabe and I. Iwata, Eiyo to Shokuryo, 1980,33,305 (Chem. Abstr., 1981, %,23 155).
N. Bluthe, J. Ecoto, M. Fetizon, and S. Lazare, J . Chem. SOC.,Perkin Trans. 1, 1980, 1747.
K. Yokoi and Y. Matsubara, Nippon Kagaku Kaishi, 1979, 641.
V. V. Kaverin and six others, Izv.Akad. Nauk SSSR, Ser. Khim., 1980, 2657.
H. D. Scharf, H. Kalkoff, and J. Janus, Tetrahedron, 1979, 35, 2513.
M. Gannon, A. Postlewhite, and R. S. McElhinney, J. Chem. Res. ( S ) , 1979, 393.
Mono terpenoids
51
(222)
(223)
(224)
(225)
and 2-methyland a l l o - o ~ i m e n e . ~
Pyrolysis
~~
of 3-methylnorpinan-2-0ne~~~
~ e r b a n o n egave
~ ~ ~the expected o-menth-3-ones but trans-verbenol was cleaved
differently to give 4-0x0-1,3,3-trimethylcyclohex-1-ene.576a-Pinene oxide was
but over salts
converted into carvacrol over Group 8 transition metals at 200 0C,577
of other metals campholenaldehyde and its 4-methyl isomer were mainly (ca. 90 %)
formed.578 P-Pinene oxide yielded p-menth-1-ene-7,8-diol on treatment with
Hg2+.57 9
Homologation, More Complicated Functiona1ization.-As an example of a genera1
synthesis of methylenecycloalkanesfrom cycloalkenes, a-pinene was coupled with
B-(cycloalkylmethyl)-9-BBN. The product was treated with CO, reduced, and
10-Trimethylfinally decomposed with PhCHO to yield 3-methylene-ci~-pinane.~~~
silyl-a-pinene on acylation (RCOC1-A1Cl3, -90 "C) gave (223) (R = Me or
CH=CMe,). The reaction also proceeded for the 7-silyl derivative of p-menth-lene, formed from P-pinene under slightly different
5-( 1,2-Diethylhepty1)resorcinol was coupled at C-4 of myrtenyl trimethylacetate to yield an
analgesic compound;582the 4-SnMe3,5834-PhS02, 4-CH20H, and 4 - m e t h ~ l e n e ~ ~ ~
derivatives have also been prepared. The lactone (224) resulted from (10-piny1)acetic acid + A c C ~and
, ~ the
~ ~corresponding saturated and unsaturated lactones
derived from the (3-0x0- lO-pinyl)-a~id~~~
and also from (225)587have been reported.
Addition of dichlorocarbeneto a- or P-pinene followed by treatment with Me3SiC1Li yielded (for the a-isomer) products (226) and (227).588Diels-Alder adducts of
10-methylene-a-pinene589
and products of annelation (with extrusion of SO2) of
@-pinenewith tetrachlorothiophen 1,l-dioxide have been
M. Nomura, Y. Fujihara, and Y . Matsubara, Yukuguku, 1979,28,919.
A. Yoshikoshi, K. Takagi, T. Nishimura, M. Iwamoto, and K. Kojo, Jap. P., 132 541/1978
(Chem. Abstr., 1979, 90, 187 171).
676 J. P. Konopelski, P. Sunderaraman, G. Barth, and C. Djerassi, J . Am. Chem. Soc., 1980,102,
2737.
6 7 6 S. Escher, W. Giersch, and G. Ohloff, Helv. Chim. Actu, 1981, 64, 934.
6 7 7 T. Kurata, Yukuguku, 1981, 30, 562.
578 K. Arata and K. Tanabe, Chem. Lett., 1979, 1017.
678 S. L. Ecoto, Eur. P., 21 952/1979.
6 B 0 H. C. Brown and T. M. Ford, J. Org. Chem., 1981, 46, 647.
681 J. P. Pillot, G. Deleris, J. Dinogues, and R. Calas, J . Org. Chem., 1979,44,3397.
6*2 R. Mechoulam, N. Lander, and S. Dikstein, U.K. P., 2 027 021/1980 (Chem. Abstr., 1981,95,
80 289).
A. N. Kashin, V. N. Bakunin, Y . K. Grishin, I. P. Beletskaya, and 0. A. Reutov, Izv. Akud.
Nauk SSSR, Ser. Khim., 1980, 1950.
684 H. Takayanage and C. Nishino, Agric. Biol. Chem., 1980,44,2877.
686 J. J. Becker, Ger. P., 3 016 111/1981 (Chem. Abstr., 1981, 94, 65 471).
686 J. J. Becker and G. Ohloff, Ger. P., 3 025 449/1981.
6a7 Z. Rykowski and Z. Chabudzinski, Pol. J . Chem., 1980, 54,741.
M. Laguerre, M. Grignon-Dubois, and J. Dunogues, Tetrahedron, 1981, 37, 1161.
68Y S. W. Markowicz and B. Bouchwic, Pol. J . Chem., 1979, 53, 221.
690 M. S. Raasch, J. Org. Chem., 1980, 45, 856.
673
674
52

*!fSiMe3
Me,Si
--- SiMe,
(226)
(227)
(228)
Myrtanyl derivatives (i.e. a-pinene substituted at C- 10)with NHNH2,591SC(CN)NR2,592OCH,SMe, and OCH,CN593 and trans-pinane substituted at C-10 with
CH,CH,NO, (from reaction of p-pinene with nitroethylene-a possibly useful
~ y n t h o n and
) ~ ~alkylated
~
at C-10 and formylated at C-3 (as intermediates en route
to prostaglandin analogues in which ether links were replaced by carbon groupi n g ~ have
) ~ ~
been
~ reported. N-Alkylmyrtenylamines are useful for optical resolution of
The use of chiral pinane derivatives-in asymmetric syntheses has
been expanded: ( +)-(3,2,1O-q-pinene)-PdI1 acetate in the presence of Cu" and
0, catalysed the asymmetric cyclization of 2-allylphenols to benzo[b]furan
derivatives,597and chiral aminyl oxides [e.g. (228)] effected enantiomeric oxidation
(7 % e.e.) of benzoin to b e n ~ i l This
. ~ ~is~a rare example of asymmetric induction
in atom transfer from carbon. The adduct of monoisopinocamphenylborane with
NNN'N'-tetramethylethylenediamine is stable and readily prepared : treatment
with BF, liberated the free b ~ r a n e . ~ ~ ~
Norpinane Derivatives.-Apopinene (6,6-dimethylnorpin-2-ene)underwent ring
cleavage on treatment with PdC1,-AcOH to give 1,2,3-trimethylbenzene by a
concerted path involving a Pd complex; this is believed to be the first reported
opening of the C4 ring of the pinane skeleton by C-1-C-7 cleavage.600Nopinone
(6,6-dimethylnorpin-2-one)
was easily synthesized from ethyl 4-oxocyclohexane-lcarboxylate,601and was readily alkylated at C-3 by organosilicon reagents802and in
the presence of ,H,O-NaOH rapidly took up one atom of tracer at C-3 via base
attack from the cis-face (steric hindrance).544The ketone has also been ring-opened
and converted into 2,2-dimethyl-4-t-butylcyclohexan-l-one603
and converted into
apoverbenone and its ring-opened
The 6,6-dimethylnorpinane
skeleton and also that of camphane were coupled via C-3 and C-4 to the N-phenyl2,4-disulphotetrahydropyrimidinering
J . N. Shah, Indian J. Chem., Sect. B., 1979, 18, 488.
K . Friedrich and M. Zamkanei, Chenz. Ber., 1979, 112, 1916.
593 J. A. Schwindeman and P. D. Magnus, Tetrahedron Lett., 1981, 22,4925.
5 84
D. Ranganathan, C. B. Rao, S. Ranganathan, A. K. Mehrotra, and R. Iyengar, J. Org. Chem.,
1980,45, 1185.
5 95 M. F. Ansell, M. P. L. Caton, M. N. Palfreymer, and K. A. J. Stuttle, Tetrahedron Lett., 1979,
4497.
5 96 S . W. Markowicz, Pol. J. Chem., 1979, 53, 157.
5 9 7 H . Hosakawa, T. Uno, S. Inui, and S. I. Murahashi, J. Am. Chem. SOC.,1981, 103, 2318.
6 9 8 C. Berti and M. J. Perkins, Angew. Chem. Int. Ed. Engl., 1979, 18, 864.
5 9 9 H. C. Brown, J . R. Schwier, and B. Singaram, J. Org. Chem., 1978, 43,4395.
6 0 0 R. M. Giddings and D. Whittaker, Tetrahedron Lett., 1978, 4077.
801 G . S. S.Murthi and A. Mazumder, Indian J. Chem., Sect. B, 198L 20, 339.
602 T. Yanami, M. Miyashita, and A. Yoshikoshi, J. Org. Chem., 1980, 45, 607.
803 J. P. Konopelski and C. Djerassi, J. Org. Chem., 1980, 45, 2297.
604
M. T. Edgar, G. Barth, and C. Djerassi, J. Org. Chem., 1980, 45, 2680.
605
A. M. Lamazouene and J. Sotiropoulos, Teirahedron, 1981, 37,2451.
5 91
5 92
Monoterpenoids
53
10 The Fenchane Class
Diels-Alder reaction of methylcyclopentadiene and CH,= CCl(CN) gave 1-methylnorborn-5-en-2-one (57 %), which was hydrogenated and methylated to fenchone
(30 %).606 endo-Fenchol on dehydration (KHS04) gave a mixture of fenchenes and
c y c l o f e n ~ h e n e s .Fenchone,
~~~
on treatment with Ph,PCH(Li)OMe-a
reagent
allegedly good for homologation of sterically hindered, enolizable ketones-gave the
endo-formylated derivative : menthone under similar conditions gave a 79 % yield
of expected products, but camphor only 10 %.608 Fenchone preferentially complexed
with P - c y c l o d e ~ t r i nand
~ ~ ~underwent Wittig addition followed by functionalization;610and the addition of the 2-lithio-derivative of anisole.6112-Diphenylmethylenefenchane (from Wittig reaction of fenchone) underwent photochemical WagnerMeerwein rearrangement, forming (229) ?, this singlet-state reaction, which in
the ground state is characteristic of species with electron-deficient carbon atoms at
the rearrangement terminus, suggests the intermediacy of a twisted excited state of
the substrate.
4i$&@
(230)
(231)
(229)
The chloride of fenchane-2-carboxylic acid decomposed (Et,N, hv) to tricyclof e n ~ h a n e . ~Thiofenchone
~
on irradiation gave (230) and the corresponding disulphide ; thiocamphor behaved similarly.614 Selenofenchone could easily be
converted into syn-2,2-bifenchylidene (231) : this is an excellent model system for
the study of hindered 01efins.~~~
11 The Thujane Class
See also ref. 58 (stereochemistry).

Occurrence.-Sabinene and trans-sabinyl acetate (ester and C,-moiety trans)
were the main components of the seed oil and foliage of Thujopsis and Arternisia
606
607
608
608
610
Ell
612
613
614
615
G . Buchbauer and H. C. Rohner, Liebigs Ann. Chem., 1981, 2093.

Y. Mutsubara and K. Yokoi, J . Chem. SOC.J., Chem. Znd. Chem., 1979, 955.
E. J. Corey and M. A. Tius, Tetrahedron Lett., 1980, 21, 3535.
J. Michon and A. Rassat, J . Am. Chem. SOC.,1979, 101, 995.
E. W. Meijer and H. Wynberg, Tetrahedron Lett., 1979, 3997.
J. L. Fry and J. W. West, J . Org. Chem., 1981, 46, 2177.
S. S. Hixson, R. 0. Day, C. S. Franke, and V. Ramachandra Rao, J . Am. Chem. SOC.,1980,
102,412.
W. Kirmse and W. Spaleck, Angew. Chem. Int. Ed. Engl., 1981, 20, 776.
D. S. L. Blackwell, K. H. Lee, P. de Mayo, G . L. R. Petrasiunas, and G . Reverdy, N o w . J .
Chim., 1979, 3, 123.
F. S. Guziec and C. J. Murphy, J . Org. Chem., 1980, 45, 2890.
54
a novel compound, was isolated

spp. r e ~ p e c t i v e l y . ~cis-Thujan-4-en-2-acetate,
~~*~~'
from a Tanaceturn sp.618
Reactions.-3-Isopropylcyclopent-2-en- 1-one reacted with Me-SOI-NaH to give

sabina ketone and sabinene oxide;619the latter could be cleaved to p-menthan-l0 1 . Thujone
~ ~ ~ and isothujone (for nomenclature see ref. 59) coupled with methyl
vinyl ketone under basic conditions to give an adduct that could be modified to
sesquithujane (e.g. cubebane) derivatives.621( -)-Isothujone with HCHO formed
the 1-hydroxymethyl derivative that underwent Jones oxidation and decarboxylation to ( + ) - t h ~ j o n e . ~ ~ ~ ? ~ ~ ~
trans-Sabinene oxide was also efficiently formed on photo-oxidation (a-diketones
as sensitizers) of ~ a b i n e n eSimilar
. ~ ~ ~ reactions of a-thujene yielded trans-thujene-3,
4-oxide, which could be converted (LiA1H4625,626
or Ni-H,627) into trans-sabinyl
hydrate (90 %). a-Thujene could be converted into the trans-4-hydroperoxyderivative of p-thujene (83%) by use of other sensitizers.628An adduct, resulting
from ring-opening and acyl-Fe(CO), insertion to yield a complex involving both
0- and n-ally1 bonding, was obtained from photolysis of ( +)-a-thujene in the presence of [Fe(CO),] or thermolysis in the presence of [Fe(CO),,]. (-)-Urnbellulone
gave an intractable complex that readily decomposed to racemic starting material.
The mechanisms of these unusual reactions are fully
Photolysis of the
thujones resulting in isomeric 1,4-dienes by extrusion of CO have been reexamined.630The lack of stereospecificity had suggested biradical mechanisms
rather than concerted chelatropic reactions with conservation of orbital symmetry.
The present work with the monoterpenes and with other bicyclo[3.1.O]hexaneswith
stereochemical markers at C-2 and C-4 led to fresh speculations about the intermediates possible within the biradical formulation. Use of deuterium tracer in
substrate and solvent showed that the isomeric thujan-3-01s and their halides
underwent super-acid (e.g. FS0,H-S02) catalysed ring-opening to the 2,3-dimethyl4-isopropylcyclopenteniumion by at least two routes that initially formed either a
carbocation or an olefin.6311632
Thujone was oxidized (KMnO,) to the a-thujaketonic
S. Hasegawa and Y . Hirose, Phytochemistry, 1981, 20, 508.

0. Vostrowsky, T. Brosche, H. Ihm, R. Zintl, and K . Knoblauch, Z . Naturforsch., Ted C,1981,
36, 369,
E. Hethelyi and seven others, Phytochemistry, 1981, 20, 1847.
O l e A. Nagakura, M. Moroe, H. Tsuruta, and T. Yoshida, Jap. P., 103 85311979 (Chem. Abstr.,
1980, 92, 75 979).
e 2 0 M. Higo, H. Toda, K. Suzuki, and Y . Nishida, Ger. P., 2 814 558/1978 (Chem. Abstr., 1979,90,
23 330).
621 J. P. Kutney, J. Balsevich, and P. Grice, Can. J . Chem., 1980, 58, 2641.
e22 C. H. Brieskorn and W. Schwack, Tetrahedron Lett., 1980, 21, 255.
e23 C. H. Brieskorn and W. Schwack, Chem. Ber., 1981, 114, 1993.
624 Lion Dentifrice K. K., Jap. P., 124 864/1978.
e25 Lion Dentifrice, K. K., Jap. P. 124 862/1978.
m e T. Shimpo, Jap. Pat., 51 030/1980.
02' T. Shimpo, H. Toda, H. Saga, K. Suzuki, and Y.Nishida, Jap. Pat., 28 965/1980.
e 2 8 Lion Corp., Jap. Pat., 75 472/1981.
S. Sarel and G . Chriki, J . Org. Chem., 1978, 43, 4971.
030 R. S. Cooke and G. D. Lyon, J . Am. Chem. Soc., 1981,103,7317.
631 J. C. Rees and D. Whittaker, J . Chem. Soc., Chem. Commun., 1978, 1096.
J. C. Rees and D. Whittaker, J. Chem. SOC.,Perkin Trans. 2, 1981, 953.
Monoterpenoids
55
acids (232) and their ring-opened products, which were starting materials for
efficient syntheses of pyrethrin a n a l o g ~ e s . ~ ~ ~ . ~ ~ ~
12 The Carane Class
A review of the class635and a detailed conformational analysis of the carane-2,3d i 0 1 s ~have

~ ~ appeared. No new naturally occurring carane derivatives, or any
unusual sources of known compounds, have been reported, but much detailed
chemistry based on (+)-car-3-ene has been carried out directed towards the
wmmercial exploitation of this major component of Indian turpentine. Syntheses
of car-2-, car-3-, and car-3( 10)-enes from cyclohex-3-en-1-one have been
developed.637
Reactions Preserving the Carane Skeleton.-Many

straightforward reactions of
( +)-car-3-ene gave expected products (usually accompanied by more or less
minor amounts of ring-opened compounds) : thus oxymercuration-demercura t i ~ nh,y~d r~~ ~g e n a t i o n formylation
,~~~
at C-3,640carbene addition,641and epoxidation followed by cleavage of the oxiran ring have been
The Prins
reaction gave 4-hydro~ymethylcar-2-ene~~~
(known) together with several interesting new minor oxygenated products :644 the main product underwent Jones oxidation
to an acid and a dimeric ester.643FriedelLCrafts acetylations gave the 4-substituted
derivatives of each carene isomer,645and the products could be e p o ~ i d i z e d , ~ ~ ~ * ~ ~
J. P. Kutney, M. K. Choudhury, J. M. Decesare, H. Jacobs, A. K. Singh, and B. R. Worth,

Can. J . Chem., 1981,59,3162.
634 J. P. Kutney, M. J. McGrath, R. N. Young, and B. R. Worth, Can. J. Chem., 1979, 57,3145
635 J. Verghese, Perfum. Flavorist, 1979, 4, 23.
636 B. A. Arbuzov, Z. G. Isaeva, I. P. Povodyreva, and V. V. Ratner, Izv. Akad. Nauk SSSR,
Ser. Khim., 1979, 2831.
637 W. Cocker and N. W. A. Geroghty, J. Chem. Soc., Perkin Trans. I , 1978, 1370.
638 E. F. Buinova, N. G. Yaremchenko, T. R. Urbanovich, and L. V. Izotova, Khim. Prir. Soedin.,
1979, 646 (Chem. Abstr., 1980, 94, 175 271).
639 I. I. Bardyshev, G. V. Deshchits and A. A. Vakhrameeva, Vestsi Akad. Navuk B. S S R , Ser.
Khim. Navuk, 1980,69.
040 M. L. Glowka, Z. Galdecki, H. Sadowska, and J. Cora, Pol. J. Chem., 1980, 54,2091.
641 D. A. Baines, W. Cocker, D. H. Grayson, P. H. Ladwa, and N. W. A. Geroghty, Proc. R.
Irish. Acad., Sect. B, 1977, 77, 323.
B. A. Arbuzov, V. V. Ratner, Z. E. Isaeva, V. N. Gudova, N. R. Rubinova, and M. E. Belyaeva,
Izv. Akad. Nauk SSSR, Ser. Khim., 1979, 1294.
643 N. E. Bhat, P. P. Pai, and G. H. Kulkarni, Chem. Ind. (London), 1981, 94.
644 N. E. Bhat, P. P. Pai, and G. H. Kulkarni, Indian J. Chem., Sect. B, 1980, 19, 316.
045 L. N. Misra and M. C. Nigam, Chem. Ind. (London), 1980, 294.
646 P. P. Pai, G. D. Joshi, K. G. Gore, and G. H. Kulkarni, Indian J. Chem., Sect. B, 1979,18,549.
6 p 7 B. B. Arbuzov, N. D. Ibragimova, and I. P. Povodyreva, Izv. Akad. Nauk, SSSR, Ser. Khim.,
633
1980, 1052.
56
hydrated,64s and further modified.649trans-4-Acetylcar-3-ene oxide was reduced

(NaBH,) to a 35 % enantiomeric excess of the I 1 R - a l c o h 0 1 . ~ ~ ~ ~ ~ ~ ~
Formation of Bicyclo [3.1.0]hexane Derivatives.-Attempted Favorskii rearrangement of 5-0x0-car-3-ene oxide mainly gave the 4-hydroxy- and the transposed
3-0x0-compound (80 %), but the remainder was the keto-acid (233).652Car-3-ene
was converted into (234), which could be cleaved to cyclopentane derivatives, by
treatment with (i) HOBr, (ii) AgNO,, and (iii) Baeyer-Villiger
but
a more efficient route utilized Tl(N03)3.654
Oxidative cleavage of the same substrate
and degradative ring closure formed 6,6-dimethylnorthujan-2-01,~~~
Several routes
have been adapted or discovered from the oxide or bromohydrin of car-3-ene to
derivatives of the transposed thujane skeleton (235).656-65s
Formation of Menthane or Cyclopropane Derivatives.-Acid

treatment of 4acetylcar-2-ene oxide gave p-menthane derivatives whereas base (NaOMe) cleaved
the oxiran ring but preserved the carane
In contrast, base treatment
(pyridine) of 2,3-dibromo-4-acetylcarane gave both p - and rn-menthane compounds
51 :49),660and dehydrogenation of car-3-ene at 4 0 0 4 5 0 "C over chromia-alumina
yielded varying proportions of p- and m-cymenes depending on the contact
times.661@2The last procedure may be of use for modifying Indian turpentine
in toto: the high content of car-3-ene allows autoxidation and renders the crude
material almost useless commercially. Chromic oxidation of car-3-ene gave
rn-cymene together with small (ca. 3 %) amounts of a dimethyldihydrotr~polone.~~~
B. M. Mane, K. G. Gore, and G. H. Kulkarni, Indian J . Chem., Sect. B, 1979, 18, 395.
Z. G. Isaeva, G. S. Bikbulatova, 0.B. Skripuik, and I. P. Povodyreva, Izv. Akad. Nauk SSSR,
Ser. Khim., 1979, 1107.
6 5 0 B. A. Arbuzov, A. N. Vereshchagin, Z. G. Isaeva, S. G. Vulfson, N. D. Ibragimova, and A. 1.
Donskova, Izv. Akad. Nauk SSSR, Ser. Khim., 1979, 1156.
651 Z. G. Isaeva, N. D . Ibragimova, I. P. Povodyreva, and T. N. Timoshina, Zzv. Akad. Nauk
SSSR, Ser. Khim., 1979, 1299.
652 B. A. Arbuzov, Z . E. Isaeva, A. N. Karaseva, and V. V. Karlin, Dokl. Akad. Nauk SSSR, 1981,
261, 887.
B. M. Mane and G. H. Kulkarni, Curr. Sci., 1981, 50, 715.
654 A. V. Pol, V. G . Naik, and H. R. Sonawane, Indian J . Chem., Sect. B, 1980, 19, 603.
655 M. Walkowicz, S. Lochynski, and C . Walkowicz, Pol. J . Chem., 1981, 55, 135.
656 B. M. Mane, K. G. Gore, and G. H. Kulkarni, Zndian J . Chem., Sect. B, 1979, 18, 395.
657 B. A. Arbuzov, Z. G. Isaeva, and R. R. Dyakonova, Izv. Akad. Nauk SSSR, Ser. Khim., 1980,
2141.
658 B. A. Arbuzov, Z . G. Isaeva, and R. R. Dyakonova, Izv. Akad. Nauk SSSR, Ser. Khim., 1980,
2778.
6 5 8 P. P. Pai, G. D. Joshi, K. G. Gore, and G. H. Kulkarni, Indian J . Chem., Sect. B., 1979,18,549.
660 L. N. Misra, and M. C . Nigam, Chem. Znd. (London), 1981, 607.
V. Krishnasamy, Aust. J . Chem., 1980, 33, 1313.
w2 V. Krishnasamy, Can. J . Chem., 1978, 56, 1994.
663 P. P. Pia, B. M. Mane, R. S. Joshi, and G . H. Kulkami, Curr. Sci., 1979, 48, 155.
648
648
Mono terpenoids
57
Derivatives of m-menthenes and m-menthadienes were also almost exclusively

produced on treatment of car-4-ene
or 5-acetylcar-2-ene
with HCl.
Reaction of car-3-ene oxide with ZnBr, gave rn-menth-5-en-2-0ne.~~~
Car-3-ene is known to be a convenient starting material for access to the irregular
chrysanthemyl skeleton (see Section 14). The (+)-olefin has been again stereospecifically converted (viahydration and oxidation) into ( +)-dihydrochrysanthemolactone and ( +)-methyl cis-chry~anthemate.~~~~~~
Other 1,2-cis-cyclopropane
derivatives have resulted from oxidative cleavage of derivatives of the same
sub~trate.~~~g-~~~
13 The Cyclopentane (Iridane) Class

See also refs. 6-8 (reviews), 35-37
69,70 (separation).
(n.m.r.), 52,63 (absolute configuration), and
Occurrence.-A review covers the I3C and lH n.m.r. of iridoid glucosides and
includes data on new
These compounds have been produced by
cultured cells of a Gardenia sp.673The insect antifeedant properties of the glucoside
ipolamide have been
The iridoid glycosides (and to a much lesser
extent the irregular monoterpenes, Section 14) are the only naturally occurring
monoterpenes that are still being discovered in large numbers. Many new iridane
derivatives with a bewildering variety of exotic names have been reported from a
range of plant genera, not all of which produce terpene alkaloids. They are
e0
OR2
664
665
667
10
..q0
CO,Me
0-,3-G
G. S . Bikbulatova, Izv. Akad. Nauk SSSR, Ser. Khim., 1978, 2380.

B. A. Arbuzov, A. N. Karaseva, and Z. G. Isaeva, Dokl. Akad. Nauk SSSR, 1979,247,364,
G . L. K. Hunter and B. C. Clark, U S . P., 4 136 119/1979 (Chem. Abstr., 1979,90, 187 172)
B. M. Mane, K. G. Gore, and G. H. Kulkarni, Indian J . Chem., Sect. B, 1980, 19,605.
N. G. Bhat, B. M. Mane, G. H. Kulkarni, and R. B. Mitra, Indian J. Chem., Sect. B, 1981,20,
204.
B. M. Mane, K. G. Gore, and G. H. Kulkarni, Indian J. Chem., Sect. B, 1980, 19, 711.
M. Kozlowska and W. Sobotka, Pol. J. Chem., 1980, 54,957.
R. B. Mitra, A. S. Khanra, and A. R. A. S . Deshmukh, Indian J. Chem., Sect. B, 1981,20,436.
672 S. Damtoft, S. R. Jensen, and B. J. Nielsen, Phytochemistry, 1981, 20, 2717.
6 7 3 S. Ueda, K. Kobayashi, T. Muramatsu, and H. Inouye, Planta Med., 1981, 41, 186.
w4 E. Bernays and C . Deluca, Experientia, 1981, 37, 1289.
670
58
mainly iridoid glucosides (236 ; R2 = p-glucose) [ring numbering in (237)], although

other sugars may be P-linked. The most comprehensive and informative papers
can be grouped into four classes dealing with the differing groups of compounds.
First (236) (R1= CO,Me, or less usually, C02H, CH20H, or CHO; R2 = pglucose.) The simplest of this group is 8-epiloganin (238) ;675 others have unsaturation in the C, ring, OH groups (sometimes oxidized, esterified, or etherified),
predominantly at C-8 and C-10 but also at C-5, C-6, C-7. and C-9, and substituents
(either a or p) in the C, ring: all functionalization can be alone or in combination.676-687An interesting sub-class has a 7,8-oxiran ring.688The second class
comprises (236; R1= H, R2 = p-glucose) with similar functional groups to the
first class,689-s92
and/or with 7,8- or 8,lO-oxiran rings.693-697
A noteworthy member
is globularidin [from Globuluria spp. (239 ; R = trans-cinnamyl)] with saturation at
C-3-C-4.697 (See also refs. 706, 707.) The third class comprises (236) (as in the
previous two classes but with R2 sugars other than glucose). Examples are compounds with cellobiose or gentiobiose p-linked at C- 1,698-700 functionalized glucose
A. Bianco and P. Passacantilli, Phytochemistry, 1981, 20, 1871.

L. Jahodar, I. Liefertova, and M. Lisa, Pharmazie, 1978, 33, 536.
6 7 7 A. Bianco, M. Guiso, C. Iavarone, P. Passacantilli, and C . Trogolo, Gazz. Chim. Ztal., 1979,
108, 13.
6 7 8 Y. Ozaki, S . Johne, and M. Hesse, Helv. Chim. Acta, 1979, 62, 2708.
0 7 0 L. M. Khatri and M. A. Kazi, J . Chem. SOC.
Pak., 1979, 1, 25.
H. Achenback, R. Waibel, and 1. Addae-Mensah, Tetrahedron Lett., 1980, 21, 3677.
081 C. W. Ford and M. R. Bendall, Aust. J . Chem., 1980, 33, 509.
S. R. Jensen and B. J. Nielsen, Phytochemistry, 1980, 19, 2685.
683 F. Bailleul, P. Delaveau, and M. Koch, Phytochemistry, 1980, 19, 2763.
684 E. Davini, P. Esposito, C. Iavarone, and C. Trogolo, Phytochemistry, 1981, 20, 1583.
m5 J. T. Huang, Arch. Pharm. (Weinheim, Ger.), 1981, 314, 831.
S . Kobayashi, Y. Imakura, Y . Yamahara, and T. Shingu, Heterocycles, 1981, 16, 1475.
6 8 7 0. Sticher and 0. Salama, Helv. Chim. Acta, 1981, 64, 78.
S. R. Jensen, C. B. Mikkelsen, and B. J. Nielsen, Phytochemistry, 1981, 20, 71.
680 K. Verma, G. R. Sood, S. R. Gupta, and V. K. Gujval, J . Chem. SOC.,Perkin Trans. I , 1979,
2473.
6 8 0 R. K. Chaudhuri, 0. Salama, and 0. Sticher, Helv. Chim. Acta, 1981, 64, 2401,
R. K. Chaudhuri and 0. Sticher, Helv. Chim. Acta, 1980, 63, 117.
Oo2 R. K. Chaudhuri, 0. Sticher, and T. Winkler, Tetrahedron Lett., 1979, 3149.
w3 F. U. Afifi-Yazar and 0. Sticher, Helv. Chim. Acta, 1980, 63, 1905.
6B4 0. Sticher and F. U. Afifi-Yazar, Helv. Chim. Acta, 1979, 62, 530.
C. Bonini, E. Davini, C . Iavarone, and C. Trogolo, Phytochemistry, 1981, 20, 1587.
S.R. Elnaggar and R. W. Doskotch, Lloydia, 1980, 43, 524.
Oo7 R. K. Chaudhuri and 0. Sticher, Helv. Chim. Acta, 1981, 64, 3.
6 s 8 A. Bianco, D. Bolli, and P. Passacantilli, Gazz. Chim. Ztal., 1981, 111, 91.
H. Achenbach, R. Waibel, B. Raffelsberger, and I. Addae-Mensah, Phytochemistry, 1981, 20,
1591.
' 0 F. Murai and M. Tagawa, Planta Med., 1979, 37, 234.
675
0'16
Mono terpenoids
59
p-linked at C- I , 701?702 diglucosides (e.g. B-glucose residues at C- 1 and C-5),703

and other sugars linked at C-6.704, 705 An oddity is (240) from a Valeriana sp. 706 The
last of the four classes comprises iridoids with no sugar residue,707-709 sometimes
extensively functionalized into a tetracyclic skeleton.710 It is not often clear whether
such compounds exist as such in vivo or whether the sugar is lost during isolation.
Several new secoiridoid g l u c ~ s i d e s ~ ~and
~ - ~a ~bis-diglucoside
*
composed of
linked iridoid and seco-iridoid units715have been isolated and characterized. Of
numerous other reports on these compounds, a selection is noteworthy in recording
new c o m p ~ u n d s , ~ascertaining
~ ~ - ~ ~ ~ or correcting structures of known com701
F. U. Afifi-Yazar, 0. Sticher, S. Uesato, K. Nagajima, and H. Inouye, Helv. Chim. Acta, 1981,
64,16.
?02
7 oa
704
A. Bianco. D. Bolli, and P. Passacantilli. Guzz. Chim. Ital., 1981, 111,479.

L. Swiatek, D. Lehmann, R. K. Chaudhuri, and 0. Sticher, Phytochemistry, 1981, 20, 2023.
A. Bianco, M. Guiso, C. Iavarone, P. Passacantilli, and 0. R. Gottlieb, Phytochemistry, 1981,
20,465.
706
A. Bianco, M. Guiso, C. Iavarone. P. Passacantilli, and C . Trogolo, Phytochemistry, 1981,20,

571.
7 06
707
708
70s
710
711
W. Kucaba, P. W. Thies, and E. Finner, Phytochemistry, 1980, 19, 575.

P. D. L. Chao and G . H. Svoboda, Lloydia, 1980,43,571.
T. Sakai, K. Nakajima, and T. Sakan, Bull. Chem. SOC.J., 1980, 53, 3683.
H. G. Grant, P. J. O'Regan, R. J. Park, and M. D. Sutherland, Aust. J . Chem., 1980, 33, 853.
E. K. Adesogan, Phytochemistry, 1979, 18, 175.
S . Uesato, T. Hashimoto, Y . Takeda, K. Uobe, and H. Inouye, Chem. Pharm. Bull., 1981,29,
3421.
712
713
D. Sainty, F. Bailleul, P. Delaveau, and H. Jaequemin, Lloydia, 1981, 44, 576.

H. Inouya, Y. Takeda, S. Uesato, K. Uobe, T. Hashimoto, and T. Shingu, Tetrahedron Lett.,
1980, 21, 1059.

S. Uesato, T. Hashimoto, and H. Inouye, Phytochemistry, 1979, 18, 1981.
715
S . R. Jensen, S . E. Lyse-Petersen, and B. J. Nielsen, Phytochemistry, 1979, 18, 273.
716 F. Bailleul, A. Rabaron, M. Koch, and P. Delaveau, Plantu Med., 1979, 37, 316.
71?
A. Bianco, M. Guiso, C. Iavarone, L. Pocaia, and C. Trogolo, Gazz. Chim. Ztul., 1979,109,561.
718
M. Tagawa and F. Murai, Planta Med., 1980,39, 144.
7 1B
T . Tsuneya, M. Ishihara, H. Shiota, and M. Shiga, Agric. Biol. Chem., 1980, 44, 957.
72 0 0. Sticher, B. Meier, D . Lehman, and I. Swiatek, PIanta Med., 1980, 38, 246.
721
S . G . Chung, B. Z . Ahn, and P. Pachaly, Arch. Pharm. (Weinheim, Ger.), 1980, 313, 702.
7aa
T. Yamauchi, F. Abe, and M. Taki, Chem. Pharm. Bull., 1981, 29, 3051.
723 J. Ruhdorfer and H. Rimpler, 2. Nuturforsch., Teil C , 1981, 36, 697.
724
J. Ruhdorfer and H. Rimpler, Tetrahedron Lett., 1981, 22, 839.
785 D. Sainty, F. Bailleul, P. Delaveau, and H. Jacquemin, Pluntu Med., 1981, 42, 260.
726
L. Swiatek, D. Lehmann, and 0. Sticher, Pharm. Actu Helv., 1981, 56, 37.
727
H. Sasaki, H. Taguchi, T. Endo, I. Yosioka, and Y. Iitrara, Chem. Phurm. Bull., 1981,29,1636.
728 Y. Nishihama, H. Masuda, M. Yamaki, S . Takagi, and K. Sakina, Pluntu Med., 1981, 43,28.
729 P. Junior, PIanta Med., 1981, 43, 34.
730 A. Bianco, M. Guiso, C. Iavarone, P. Passacantilli, and C . Trogolo, PIuntu Med., 1981, 41,
75.
731 A. Bianco, P. Passacantilli, and G . Polidori, Lloydiu, 1981, 44, 732.
732 A. Bianco, D. Bolli, and P. Passacantilli, Lloydiu, 1981, 44,448.
733 C. Adriani, C. Bonini, C. Iavarone, and C. Trogolo, Lloydiu 1981,44, 739.
734 H. Thomas and H. Budzikiewicz, Phytochemistry, 1980, 19, 1866.
714
60
pounds, 735-737 and documenting rare occurrences and unexpected sources. 738-745
Of especial interest is a revision of the structure of xylomollin: synthetic and
spectroscopic studies and X-ray analysis of the 1-0-acetyl derivative show it to be
the first characterized example of a naturally occurring trans-fused iridoid. 746
Synthesis and Reactions.-The absolute configuration of boschnaloside has been

elucidated by chemical correlation with asperuloside. 747 Several routes to simple
cyclopentane derivatives have been modified or discovered : a particularly elegant
synthesis involved cycloaddition of trimethylenemethane complexed to transition
metals, e.g. from reaction of (241) or (242) with [Pd(PPh,),], to cyclopent-2-en-lone to give a bicyclo[3.3.0]octane derivative that could be ring-opened to chrysomelidial (243).748Compound (243), together with (244), was formed by a six-stage
route from l i r n ~ n e n and
e ~ ~it~was proved that the latter was not g a s t r ~ l a c t o n e , ~ ~ ~
which was suggested to be the isomeric 7-ene.749This supposition was confirmed
by a six-step synthesis from carvenolide. 751 Compound (243) was also synthesized
in a multi-step process from diethyl 2-cyclopenten-1-ylmalonate.752 Routes from
geraniol to (245) and thence to ( f)-iridomyrmecin, 753 from 2-methyl-5-chlorocyclopentane-1-carboxylicacid to the nepetalinic acids and photocitral A,754and to
other key intermediates for the synthesis of iridoids have been described. 755
Cyclocitral was converted into trans,cis-d~lichodial~~~
and p-menth- 1-ene into
chamigrene and acorenone B.757A synthesis of the alleged genipic acid by photoannelation unambiguously showed that the proposed structure (which had been
doubted by some) was incorrect.758
735
G . J. Kapadia, Y. N. Shukla, A, K . Bose, H. Fujiwara, and H. A. Lloyd, Tetrehedron Lett.,

1979, 1937.
736
737
738
73n
740
742
743
744
745
M. R. Bendall, C. W. Ford, and D. M. Thomas, Aust. J . Chem., 1979,32,2085.

S . R. Jensen, B. J. Hielsen, C. B. Mikkelsen, J. J. Hoffman, S. D. Jolad, and J. R. Cole,
Tetrahedron Lett., 1979, 3261.
A. Sutarjadi, T. M. Malingre, and F. H. L. van Os, Phytochemistry, 1978, 17, 564.
R. K. Chaudhuri and 0. Sticher, Plantu Med., 1980, 39, 140.
Y. Takeda and T. Fujita, Planta Med., 1981, 41, 192.
C. B. Rao, E. K. S. Vijayakumar, and K. U. Vijayalakshmi, Planta Med., 1981, 41, 80.
G. Lammel and H. Rimpler, Z . Nuturforsch., Teil C, 1981, 36, 708.
R. K . Chaudhuri, 0. Salama, and 0. Sticher, Tetrahedron Lett., 1981, 22,4061.
A. Bianco, A. Francesconi, and P. Passacantilli, Phytochemistry, 1981, 20, 1421.
E. K. Adesogan and F . N. Morah, Phytochemistry, 1981, 20,2585.
M. Nakane, C. R. Hutchinson, D. van Engen, and J. Clardy, J. Am. Chem. SOC.,1978, 100,
7079.
F. Murai and M. Tagawa, Chem. Pharm. Bull., 1980,28, 1730.
'748 B. M. Trost and D. M. T. Chan, J . Am. Chem. SOC.,
1981,103, 5972.
748 T. H . Jones, M. S . Blum, and H. M. Fales, Tetrahedron Lett., 1980,21, 1701.
750 M. S. Blum, J. B. Wallace, R. M. Duffield, J. M. Brand, H. M. Fales, and E. A . Sokoloski,
J . Chem. Ecol., 1978, 4,47.
751 T. H. Jones and M. S . Blum, Tetrahedron Lett., 1981, 22,4373.
7 5 2 K. Kon and S . Isae, Tetrahedron Lett., 1980, 21, 3399.
753 Y. Yamada, H . Sanjoh, and K. Iguchi, Chem. Lett., 1978, 1405.
754 T. Sakai, K. Morita, C. Matsumura, A. Sudo, S. Tsuboi, and A. Takeda, J . Org. Chem., 1981,
46,4774.
755 T. Imagawa, T. Sonobe, H. Ishiwari, T. Akiyama, and M. Kawanisi, J . Org. Chem., 1980,45,
2005.
756 C. Beaupin, J. C. Rossi, J. P. Vidal, J. P. Girard, and J. Passet, Phytochemistry, 1980,19, 1541.
7 5 7 J. D. White, J. F. Ruppert, M. A. Avery, S . Torii, and J. Nokami, J . Am. Chem. SOC.,1981,103,
1813.
768 S . W. Baldwin and M. T. Crimmins, J . Am. Chem. SOC.,1980, 102, 1198.
747
Monoterpenoids
61
Dolichodiol was converted into iridoid lactones by the N-halogenosuccinimide-Me,S complex. 759 A new synthesis of loganin and related compounds
started with the regioselective sulphenylation of P-keto-esters (such as ethyl
2-oxocyclopentane- l-carboxylate) followed by conversion into the p-thioalcohols,
oxidative cleavage, and c y c l i ~ a t i o nA. ~most
~ ~ impressive route to the skeleton (237)
involved a rare type of intramolecular ene reaction of (246).761Cyclization of (247).
prepared by Wittig reaction of diethyl oxomalonate, gave elenolic acid. 762
Eight- to sixteen-step syntheses of isoiridomyrmecin and verbenalol, 763 iridomyrrne~in'~*
allodolicholactone (first synthesis), iridomyrmecin and its i ~ o - e p i m e r ~ ~ ~
and ~ a r r a c e n i nhave
~ ~ ~been reported.
The aglycones of a s p e r ~ l o s i d o and
l ~ ~ ~its derivatives76s rearranged in acid to
tetracyclic acetals : under similar conditions other iridoid glucosides (harpagide,
antirrhide) opened to cyclopentane derivatives,768 and lamiigenin was similarly
cleaved by NaBH, in a Knoevenagel-type process. 769 C a t a l p 0 1 ~and
~ ~ other
lactones771 have been reduced and functionalized, geniposide has been converted
by a biogenetic-type transformation into p l ~ m i e r i d e , ~
aucubin
~,
has been used as a
starting material for prostaglandin
and attempts have been made to
convert the aglucone of kingiside into xylomollen. 774
Secologanin on enzymic cleavage, acid treatment, and oxidation gave elenolide
(248), and the sequence established the chirality as shown at the point of attachment
of the side-chain. 7 7 5 [10-13C]Secologaninwas synthesized in a seven-step process
from ethylene a ~ e t a lHop
. ~ ~ether
~ (249), the irioid most simply related to geraniol,
was synthesized in six steps from the protected lactol form of 3-formyl-2-methoxycarbonylcyclopentanol. 7 7 7
14 The Irregular Classes

The chemistry of the pyrethroid acids has been reviewed.778In the following
sections; A, S, and L represent compounds with the artemisyl, santolinyl, and
lavandulyl skeleta respectively.
F. Bellesia, R. Grandi, U. M. Pagoni, and R. Trave, J. Chem. SOC.,Perkin Trans. 1, 1979, 851.
K. Hiroi, H. Miura, K. Kotsuji, and S . Sato, Chem. Lett., 1981,559.
B. B. Snider and J. V. Duncia, J. Org. Chem., 1980, 45, 3461.
B. B. Snider, D. M. Roush, and T. A. Killinger, J. Am. Chem. SOC.,1979, 101,6023.
763 P. Callant, R. Ongena, and M. Vandewalle, Tetrahedron, 1981, 37, 2085.
704 P. A. Grieco and C. V. Srinivasan, J. Org. Chem., 1981, 46, 2591.
765 K. Schaffner and M. Demath, Chimia, 1981, 35,437.
788 J. K. Whitesell, R. S. Mathews, M. A. Minton, and S. M. Helbling, J. Am. Chem. SOC.,1981,
750
760
103,3468.
767
768
76*
'70
771
A. Bianco, M. Guiso, C. Iavarone, P. Passacantilli, and C. Trogolo, Tetrahedron, 1980, 36,

1613.
A. Bianco and P. Passacantilli, Guzz. Chim. Ztul., 1981, 111, 223.
A. Bianco, D. Budai, M. Guiso, C. Iavarone, R. M. Bettolo, and C. Trogolo, Guzz. Chim. Ztul.,
1979,109, 517.
K. Weinges, H. von der Eltz, and D. Tran-Viet, Angew. Chem. Znt. Ed. Engl., 1980, 19, 628.
F. Bellesia, U. M. Pagnoni, R. Trave, G. D. Andreetti, G. Bocelli, and P. Sgarabotto, J. Chem.

SOC.,Perkin Trans. 2, 1979, 1341.
772
773
775
776
777
778
K. Inoue, Y. Takeda, H. Nishimura, and H. Inouye, Chem. Pharm. Bull., 1979, 27, 3115.
M. Naruto, K. Ohno, and N. Naruse, Chem. Lett., 1978, 1419.
S. B. Hassam and C. R. Hutchinson, Tetrahedron Lett., 1980, 21, 1209.
L. F. Tietze and H. C. Uzar, Angew. Chem. Znt. Ed. Engl., 1979, 18, 539.
L. F. Tietze and S. Henke, Angew. Chem. Znt. Ed. Engl., 1981, 20,970.
T. Imagawa, N. Murai, T. Akiyama, and M. Kawanisi, Tetrahedron Lett., 1979, 1691.
D. Arlt, M. Jautelat, and R. Lantzsch, Angew. Chem. Znt. Ed. Engl., 1981, 20, 703.
62
Occurrence.-( +)-Artemisia alcohol [rather than the usual (-)-enantiomer],

yomogi alcohol (class A), santolina alcohol and triene, lyratol (class S), and epoxyartemisia ketone occur in Artemisia779?780
and Chrysanthemum
Santolinide B
(250) and lesser amounts of isomeric lactones occur in Arternisia spp.
According to the revised hypothesis concerning the biosynthesis of the A, S , and L classes,
(lR,3S)-cis-chrysanthemyl alcohol should be the precursor of these lactones as they
possess the S-configuration at C-3. 782 Achillene (2,5-dimethyl-3-vinylhexa1,4diene; class S) has been isolated from an Achillea sp.784One of the many investigated chemotypes of Tanaceturn vulgare produced y-campholenol (251), a new
compound, as well as artemisyl and lyratyl derivatives.618The claimed first C,,
acetylenic lactone was found in a Senecio sp.,785but this had the 2-methylnonane
skeleton and may not be of isoprenoid origin ; 1,5,5-trimethylcyclohepta-l,3,6triene occurs in a Pinus sp.;786
nor-monoterpenes with the 2,5- and 2,6-dimethylheptane skeleta are insect sex pheromones, 7 8 7 and ilex lactone is a bis-nor-monote~pene.~~~
782p783
(253)
(254)
Syntheses and Reactions.-Coupling of 3-methyl-1-trimethylsilylbut-2-ene with

3,3-dimethylacryl chloride yielded artemisia ketone. 7 8 9 Reaction of 2,5-dimethylhexa-2,4-diene with ClCH2CN (CuC1, 2,2'-bipyridyl catalysts) gave l-cyano2,2,5-trimethylhexa-3,5-diene
(Class A). 790 Lavandulol has been efficiently (3055 %) synthesized from 6-chloro-2,6-dimethylhept-2-ene,
791 2,6-dimethylhepta-2,5diene,792-794
and 3,3-dimethylacryl acetate795and by coupling of the lithiated
77g
780
781
782
783
784
785
786
787
R. Segal, A. Brever, and I. Feuerstein, Phytochemistry, 1980, 19, 2761.

R. Haf-Muller, W. Pickenhagen, and B. Willhalm, Helv. Chim. Acta, 1981, 64, 1424.
F. Bohlmann and U . Fritz, Phytochernistry, 1979, 18, 1888.
W. W. Epstein and L. A. Gaudioso, J . Org. Chern., 1979, 44, 31 13.
S. K. Pakniker and J. Veeravalli, Indian J . Chern., Sect. B., 1979, 18, 269.
A. Dembitskii, M. I. Goryaev, R. A. Yurina, A. E. Lyuts, and S . M. Vasilyuk, Izv. Akad.
Nauk Kaz. S S R , Ser. Khim., 1978, 28,45.
F. Bohlmann, C. Zdero, R . M. King, and H. Robinson, Phytochemistry, 1981, 20, 2425.
E. M. Manukov, V. A. Chuiko, and P. V. Kuzmichkin, Khim. Prir. Soedin., 1979, 783.
M. Uchida, K. Nakagawa, T. Negishi, S . Asano, and K. Mori, Agric. Biol. Chem., 1981, 45,
369.
788
789
7g0
7g1
7g2
7e3
784
'g6
H. Thomas and H. Budzikiewicz, Phytochemistry, 1980, 19, 1866.

G. Delaris, J. P. Pillot, and R. C. Rayer, Tetrahedron, 1980, 36, 2215.
M. Julia, G. Lethuillier, and L. Saussine, J . Organomet. Chem., 1979, 177, 211.
H. E. Du Preez, C . F. Garbers, and J. A. Steenkamp, S . Afr. J . Chem., 1980, 33, 21.
M. Takami, Y.Omura, K. Itoi, and T. Kawaguchi, Jap Pat., 98 915/1978 (Chem. Abs., 1979,
90, 23 328).
R. C. Cookson and N. A. Mirza, Synth. Commun., 1981, 11, 299.
Y .Ueno, S . Aoki, and M. Okawara, J . Chem. Soc., Chem. Commun., 1980,683.
M. Julia, C. Perez, and L. Saussine, J . Chem. Res. ( S ) , 1978, 311.
Monoterpeno ids
63
derivative of an A"'-disubstituted amide of 3,3-dimethylacrylic acid with 3,3dimethylallyl

the last is an interesting example of a general reaction
whereby the lithium derivative reacts with a variety of electrophiles to give a
deconjugated, a-alkylated product. Isodihydrolavandulo17g7and the furanomonoterpene evodone (class L)798have been synthesized from (I?)-( +)-citronelk acid.
Syntheses of chiral lyratyl acetate,799artemiseole (252),800~s01
the lactone (253),801~802
and m a r m e l ~ l a c t o n ehave
~ ~ ~been reported: the last is a rare example of a 'tail-totail' linked monoterpene.
A few cyclobutane derivatives have been investigated. Lineatin (254), a beetle

pheromone, was prepared in a route allowing optical resolution of an intermediate,
and hence synthesis of both e n a n t i o m e r ~Filifolone
.~~~
(255) can be obtained from
intramolecular alkylation of (256) : the latter was easily prepared from heptadienyl
nitrile and was claimed to be useful generally as a terpene
Photolysis
of verbanone gave a substituted cyclobutaldehyde that could be elaborated to the
pheromone (257),806and (258) was prepared from methyl cyclobut-l-enecarboxylate.807 Eucarvone resulted from an elegant ring expansion of 5,5-dimethylcyclohex-2-en-l-one.808 Amino and hydroxyl derivatives of e u c a r v ~ n eand
~~~
karahanaenone810 and other 2,2,5-trimethyl~ycloheptanones~~~
have been synthesized. y,&Epoxyeucarvone was rearranged into isomeric trimethylcyclopenta[b]furans. 812 Friedel-Crafts acylation of tropone irontricarbonyl gave a mixture of
tautomers which were convertible into P-thujaplicir~.~~~
Cryptone (a nor-monoterpene) resulted from Lewis acid-catalysed ring cleavage of nopinone. 814
The volume of work on the chrysanthemyl class reflects the importance of these
compounds as insecticides. Several new syntheses of the isomeric chrysanthemic
M. Majewski, G. B. Mpango, M. T. Thomas, A. Wu, and V. Snieckus, J. Org. Chem., 1981,
46,2029.
7 8 7 J. N. Shoolery and E. W. Southwick, J. Agric. Food Chem., 1980, 28, 302.
Y. Masaki, K. Sakuma, K. Hashimoto, and K. Kaji, Chem. Lett., 1981, 1283.
R. G. Gaughan and C. D. Poulter, J. Org. Chem., 1979, 44, 2441.
D. V. Banthorpe and P. N. Christou, Phytochemistry, 1979, 18, 666.
D. V. Banthorpe and P. N. Christou, J. Chem. SOC.,Perkin Trans. I , 1981, 05.
S . Yamagiwa, H. Kosugi, and H. Uda, Bull. Chem. SOC.J., 1978, 51, 301 1.
K. Mori and M. Sasaki, Tetrahedron, 1980, 36, 2197.
804 T. Hudlicky and T. Kutchan, Tetrahedron Lett., 1980, 21, 691.
A. B. Smith, B. H. Toder, S. J. Branca, and R. K. Dieter, J. Am. Chem. SOC. 1981,103, 1996.
*06 B. A. Bierl-Leonhardt, D. S. Moreno, M. Schwarz, J. Fargerlund, and J. R Plimmer. Tetruhedron Lett., 1981, 22, 389.
807 R. D. Clark, Synth. Commun., 1979, 9, 325.
L. Blanco, N . Slougui, G. Rousseau, and J. M. Conia, Tetrahedron Lett., 1981, 22, 6 4 5 .
Bop I. Mielczarek and F. Rulko, Pol. J . Chem., 1980, 54,419.
N. Shimuzu and Y. Tsuno, Chem. Lett., 1979, 103.
A. Itoh, K. Oshima, H. Yamamoto, and H. Nozaki, Bull. Chem. SOC.J., 1980, 53, 2050.
K. Tsutsumi and H. R. Wolf, Helv. Chim. Actu, 1980, 63, 2370.
M. Franck-Neumann, F. Brion, and D. Martha, Tetrahedron Lett., 1978, 5033.
B. B. Snider, D. J. Rodin, and J. van Straten, J. Am. Chem. SOC.,1980, 102, 5872.
786
64
acids have been developed.815-822Perhaps the two most intere$ng used 2,5dimethylhex-3-yne-2,5-diol
(commercially available) as starting materia1,"l or involved addition to 3,3-dimethylacrylate esters of the thiovinylcarbene formed on
photolysis of gern-dimethyl-5-ethylthiopyra-a~olenine.~~~
Ethyl 2-bromo-3,3-dimethylacrylate is a new synthon for p y r e t h r o i d ~ and
, ~ ~ ~useful intermediates for
these compounds could be prepared from ~ a r - 3 - e n eThe
. ~ ~ difference
~
of the 13C
n.m.r of the gem-dimethyls shows whether chrysanthemate derivatives are cis or
trans;825homogenous Pd complexes are excellent catalysts for the cis+trans isomerizations.826 Photosensitized oxidation of trans-chrysanthemic acid gave the
expected
the epoxides of both cis- and trans-acids and of pyrethrins
were decarboxylated readily ( e . g . o n t.l.c.).82R
A variety of chrysanthemic ester analogues with ~ h l o r i n e ~ or
~ ~other
-*~~
substituents (e.g. Br, SMe, or CN)833-836
on the double bond or on the ring,837and of
substituted cyclobutanones that are precursors of pyrethroids, have been obtained
by more or less standard routes. 838-840 The absolute configurations of synthetic
pyrethroids containing the a-ethylvinyl alcohol moiety have been determined84L
and p h o t ~ c h e r n i c a l ~
and
~ ~enzymic
- ~ ~ ~ (esterases from worm larvae)846degradations
of pyrethroids have been elucidated.
M. J. de Vos and A. Krief, Tetrahedron Lett., 1979, 1511.

M. J. De Vos and A. Krief, Tetrahedron Lett., 1979, 1891.
B. J. Fitzsimmons and B. Fraser-Reid, J . Am. Chem. Soc., 1979, 101, 6123.
M. Franck-Neumann and C. D. Buchecter, Tetrahedron Lett., 1980, 21, 671.
N. G. Bhat, G . D. Joshi, K. G. Gore, G . H. Kulkerni, and R. B. Mitra, Indian J . Chem.,
Sect. B., 1981, 20, 558.
820 D. Babin, J. D. Fourneron, L. M. Harwood, and M. Julia, Tetrahedron, 1981, 37, 325.
821 J. P. Gen&t, F. Piau, and J. Ficini, Tetrahedron Lett., 1980, 20, 3183.
822 M. Franck-Neuman and J. J. Lohmann, Tetrahedron Lett., 1979, 2075.
823 J. H. Babler and B. J. Invergo, Tetrahedron Lett., 1981, 21, 2743.
824 T. L. Ho and Z. U. Din, Synth. Commun., 1981, 10, 921.
825 L. Crombie, G. Kneen, G . Pattenden, and D. Whybrow, J . Chem. Soc., Perkin Trans. I , 1980
1711.
828 J. L. Williams and M. F. Rettig, Tetrahedron Lett., 1981, 21, 385.
827 A. A. Frimer, Zsr. J . Chem., 1981, 21, 194.
828 I. H. Smith and J. E. Casida, Tetrahedron Lett., 1981, 21, 203.
P. Martin, H. Greuter, and D. Bellus, J . Am. Chem. Soc., 1979, 101, 5853.
830 W. G . Taylor, Synthesis, 1980, 554.
831 T. Shono, H. Ohmizu, S. Kawakami, S. Nakamo, and N. Kise, Tetrahedron Lett., 1981,21,871.
832 P. D. Klemmenson, H. Kolind-Andersen, H. B. Modsen, and A. Svendsen, J . Org. Chem.,
1979, 44,416.
833 D. Holland and D . J . Milner, J . Chem. Res. ( S ) , 1979, 317.
834 M. B. Green, G. S. Hartley, and T. F. West, 'Chemicals for Crop Protection and Pest Control',
Pergamon, Oxford, 1977, p. 83.
835 0. Ruel, B. Cazes, and S . Julia, Synth. Commun., 1980, 10, 743.
836 J. P. Gen&tand F. Piau, J . Org. Chem., 1981, 46, 2414.
8 3 7 M. J. DeVos and A. Drief, Tetrahedron Lett., 1979, 1515.
838 P. Martin, H. Greuter, G. Rihs, T. Winkler, and D. Bellus, Hefv. Chim. Acta, 1981, 64, 2571.
839 P. Martin, E. Steiner, and D. Bellus. Helv. Chim. Acta, 1980, 63, 1947.
8 4 0 P. Martin, H. Greuter, and D. Bellus, Helv. Chim. Acta, 1981, 64, 64.
841 N. Matsuo, T. Yano, and H. Yoshida, Agric. Biol. Chem., 1981, 45, 1915.
842 L. 0. Ruzo and J. E. Casida, J . Chem. Soc., Perkin Trans. I , 1980, 728.
843 Y. Kawano, K. Yanagihara, T. Miyarnoto, and 1. Yamamato, J . Chromatogr., 1980, 198, 317.
844 L. 0. Ruzo, L. C. Gaughan, and J. E. Casida, J . Agric. Food Chem., 1980, 28, 256.
845 L. 0. Ruzo and J. E. Casida, J . Agric. Food Chem., 1981, 29, 702.
848 A. A. I. Yehia and D. M. Soderlund, Pestic. Biochem. Physiol., 1980, 14, 282.
el5
Monoterpenoids
65
15 Cannabinoids and Other Phenolic Monoterpenoids
See also ref. 2 (review).

Cannabinoids.-New compounds (259; OH at C-8 or at C-10)S47and (259; OH at
both C-9 and C-10)S4Shave been isolated from Cannabis sativa. p-Menth-2-ene-1,8diol is an excellent synthon for the Ag-tetrahydrocannabinol (THC) skeleton,
coupling (ZnC1,-catalysed) with olivetol (3-n-pentylresorcinol) to form the (-)parent compound, and forming the biologically potent 3-OH metabolite by
appropriate modification of the reaction.S49The structurally equivalent substrate
p-menth- 1,8-dien-l-ol reacted with other substituted resorcinols and led to AS- and
A9-THC analogues differing in the side-chain attached at C-3.S50-S51
Use of the
synthon (260) in a similar manner gave 2', I 1 -dihydroxy-Ag-THC: this was claimed
'i
QH
?!
OH
(259)
. ,
(260)
to be the first synthesis of a metabolite functionalized in both the terpenoid moiety
and in the ~ i d e - c h a i nCoupling
.~~~
of pulegone with 3-X-resorcinols (X= C5HII or
Me), protection of the phenolic group with SiMe,Bu', bromination and aromatization (NBS,hv) of the C, ring, and deprotection gave improved routes, claimed the
best available, to cannabinol and cannabiorcol respectively.853The bis-tetrahydropyranyl homocuprate of olivetol reacted with dehydrolinalool (in a reaction general
for propargylic halides and acetates) to give a versatile synthesis of cis-6a,lOa-AsTHC. 854 A modification of a previously described synthesis of this by condensation
of olivetol with citral opened a convenient route to the t r a n s - i ~ o m e r AS-THC
.~~~
with a modified side-chain at C-3 resulted from reaction of the appropriate resorcIn yet another
inol derivative with trans-verbenol in the presence of a Lewis
variant of the general method, substituted resorcinols reacted with the enolate of
( +)-citronella1 to give an intermediate which underwent a stereocontrolled
[4 + 21 heterodiene cycloaddition to give (261). The structure and conformation of
847
848
849
850
851
863
854
E55
M. A. Elsohly, E. E. Boeren, and C. E. Turner, Experienfia, 1978, 34, 1127.

E. G. Boeren, M. A. Elsohly, and C. E. Turner, Experientiu, 1979, 35, 1278.
G. R. Handrick, D. B. Uliss, H. C. Dalzell, and R. K. Razdan, TetrahedronLett., 1979, 681,
I. Franke and M. Binder, Helv. Chim. Actu, 1980, 63, 2508.
C. G. Pitt, H. H. Seltzman, Y . Sayed, C. E. Twine, and D . L. Williams,./. Org. Chem., 1979,44,
677.
R. P. Duffley, G . Lambert, H. C. Dalzell, and R. K. Razdam, Experientia, 1981, 37, 931.
P. C. Meltzer, H. C. Dalzell, and R. K. Razdam, Synthesis, 1981, 985.
J. M. Luteijn and H. J. W. Spronck, J . Chem. SOC.,Perkin Trans. I , 1979, 201.
V. Chandrasekharan, P. Unnikrishnan, G . D. Shah, and S . C . Bhattacharyya, Indim J . Chem.
Sect. B, 1980, 19, 746.
66
this were elucidated by 13Cn.m.r. and X-ray analysis.856Less general syntheses have
been carried through for hydroxylated and oxidized derivatives of AS-THC
functionalized in the ~ i d e - c h a i or
n ~at~ ~C-1 1,868-859
for derivatives of As-THC with
the side-chain completely modified (262) (R = Ar or CR=CR2),s60and for sidechain analogues of AsaJoa-THC.8s1Most of the compounds were required for
testing as potential therapeutic agents. A8-THC glucoronide has been synthesized
and its metabolism in rats investigated.s62 [ 1 1-2H,]-cis-6a,10a-A9(11)-THC and its
trans-isomer were easily prepared from [ 1-2H, ] g e r a n i ~ and
l ~ ~14C~ and 1251-labelled
cannabinoids have also been ~ynthesized.~~~9
865 Citronella1 condensed with barbituric acid and related compounds to form enantiomeric tricyclic dihydropyrans
that are cannabinoid analogues. 866
Bucourts method for estimation of torsional strain can be successfully applied
to the THC ring system to give a surprisingly good quantitative estimate of the
relative stability of the various double-bond isomers, in particular of the position of
equilibrium for As +A9 for the parent and model compounds demethylated at C-6. 667
The long-range 1,5-substituent effect of an ester group at C-1 was held to be
responsible for the base-catalysed conversion of a methoxycarbonyl group at C-9
from an equatorial to an axial position. The axial isomer was unchanged in the
reaction conditions. A similar effect, presumably due to flexing of the carbocyclic
skeleton, was found in elimination : dehydrochlorination of the 9-chloro- l-hydroxycompound and of the 9-chloro- 1-methoxy-compound gave the isomeric As- and
119-compoundsrespectively.s68The degradation of As- and AS-THC via the epoxy
and hydroxylated derivatives has been reported. s69
Thymol Derivatives.-Occurrence. Several new thymol derivatives have been

isolation of (263) from roots of a
obtained from a variety of plant
Marshallia sp. was claimed to have chemotaxonomic significence.872 Isothymol
(rn-menthane skeleton) and its esters occur n a t ~ r a l l y a; ~phenolic
~ ~ ~ ~ ether
~~
L. F. Tietze, G. von Kiedrowski, K. Harms, W. Clegg, and G. Sheldrick, Angew. Chem. Znt.
Ed. Engl., 1980, 19, 134.
857 A. Ohlsson, S. Agurell, K. Leander, J . Dahmen, H. Edery, G . Porath, S. Levy, and R. Mechoulam, Acta Pharm. Suec., 1979, 16, 21 (Chem Abs., 1979, 91, 108092).
R. S. Wilson, B. R. Martin, and W. L. Dewey, J. Med. Chem., 1979, 22, 879,
859 R. S. Wilson, E. L. May, and W. L. Dewey, J. Med. Chem., 1979,22, 886.
860 P. Unnikrishnan, V. Chandrasekharan, G . D. Shah, and S. C. Bhattacharyya, ZndimJ. Chem.,
Sect. B, 1979, 17, 250.
P. C. Meltzer, H. C. Dalzell, and R. K. Razdan, J. Chem. Soc., Perkin Trans. I , 1981, 2825.
862 H. Yoshimura, K . Watanabe, and K. Oguri, Chem. Pharm. Bull., 1979, 27, 3009.
863 R. A. Driessen and C. A. Salemink, Recl. Trav. Chim. Pays-Bas, 1981, 100, 342.
864 Y. Shoyama, H. Hirano, and 1. Nishioka, J. Labelled Comp. Radiopharm., 1978, 14, 835.
865 C. G. Pitt, H. H. Seltzman, S. R. Setzer, and D. L. Williams, J. Labelled Comp. Radiopharm.,
1980, 17, 68 1 .
L. F. Tietze and G. von Kledrowski, Tetrahedron Lett., 1981, 22, 219.
H . C. Dalzell, D. B. Uliss, G. R. Handrick, and R. K . Razdan, J. Org. Chem., 1981, 46, 949.
8E8 R. Mechoulam, N. Lander, I. Tamir, Z. Ben-Zvi, and Y. Kimmel, Angew. Chem. Znt. Ed.
Engl., 1980, 19, 543.
869 C. E. Turner and M. A. Elsohly, J. Heterocycl. Chem., 1979, 16, 1667.
F. Bohlmann and J . Jakupovic, Phytochemistry, 1979, 18, 631.
F. Bohlmann, A. Krishendhar, and M. Ahmeij, Phytochemistry, 1980, 19, 1850.
8 7 2 F. Bohlmann, J . Jakupovic, R. M. King, and H. Robinson, Phytochemistry, 1980, 19, 1815.
8 7 3 F. Bohlmann, A. A. Natu, and K. Kerr, Phytochemistry, 1979, 18,489.
. 3 R.
~
Shmitz, G . Shaden, and H. Kating, Arch Pharm. (Weinheim, Ger.), 1979, 312, 65.
856
Monoterpenoids
67
f OCOBut
(OCOPr
QAc
previously isolated875is the 3-methyl-2-isopropenyl derivative (rather than the

2-methyl-3-isopropenyl compound).876
Reactions. Grignard reaction and hydrogenation of the appropriate methyl aryl
ketone yielded i s o t h y m 0 1 . ~Carvacrol
~~
was formed in excellent (83 %) yield on
heating p-menth-l-ene oxide with Pd.878Aromatic aldehydes can be protected in situ
by formation of a-aminoalkoxides and their O-trimethylsilyl ethers : thus 4-formylbenzoic acid could be protected and elaborated (Grignard reaction) into (264).879
Esters of thymol underwent photo-Fries rearrangement to 2-acyl derivatives of
thymo1.880Thymol methyl ether was brominated in the isopropyl group and also
para to the methoxy-group by NBS.881Earlier work on the spectrum of mono-,
di-, and tri-brominated products in the side-chain of p-cymene formed by reaction
of NBS has been amended and corrected.882Oxidation of thymol acetate with
benzyltrimethylarnmonium permanganate gave 3-hydroxy-4-isopropylbenzoic
acid,
which could be elaborated to the natural product (265).883Compound (266), also
naturally occurring, was synthesized by base-promoted ring-opening of (267).884
16 Biogenesis, Chemotaxonomy, Biological Applications

See also refs. 9-11 (books), 12-20 (reviews), 22 (tissue culture), 23 (chemotaxonomy), and 24 (biological functions).
876
876
877
879
880
882
884
R. Sangaiah and G. S. Krishna Rao, Tetrahedron Lett., 1981, 22, 1843.

R. Bohlmann and A. Suwita, Phytochemistry, 1978, 17, 560,
A. S. Dinge, J. K. Kirtany, and S. K. Paknikar, Indian J. Chem., Sect. B, 1981, 20, 245.
T. Kurata, Yukugaku, 1979, 28,407.
D. L. Comins and J. D. Brown, Tetrahedron Lett., 1981, 22, 4213.
V. P. Pathak and R. N. Khanna, Synthesis, 1981, 882.
V. V. Dhekne, A. R.A. S.Deshumkh, and A. S. Rao, Indian J . Chem., Sect. B, 1980,19, 188.
B. Ravindranath and P. Srinivas, Indian J. Chem., Sect. B, 198 1, 20, 165.
R. Sangaiah and G. S. Krishna Rao, Synthesis, 1980, 1018.
Y.S. Sanghui and A. S . Rao, Indian J. Chem., Sect. B, 1980, 19, 952.
68
Labelling Patterns; Cell-free Extracts.-C-I0 of geraniol, synthesized in Rosa spp.

was exclusively derived from C-2 of MVA.885This had been previously tacitly
assumed and used in mechanistic discussions concerning IPP-isomerase. Feeding
of 14C- and 3H-labelled geraniol and MVA to a Mentha sp. showed that: (i) oxidation of limonene or its biogenetic equivalent to form carvone involved shift of the
endocyclic double bond and (ii) the exocyclic double bond in the product was not
formed regiospecifically.886 The gem-dimethyls of pulegone were also scrambled in
its formation from [10-14C]geraniol by another Mentha sp.887 Measurement of
isotope ratios in car-3-ene biosynthesized in a Pinus sp. from 14C,3H-labelledMVA
and geraniol revealed that the carane skeleton was constructed from its presumed
monocyclic precursor with migration of a double bond together with an unexpected
1,2-shift of a proton to the site of the original unsaturation. The detailed stereochemistry of the processes allowed a two-step mechanism to be inferred for the
cyclization, in whch a bonded intermediate was involved,888e . g . (268)+(269), Z
and Y being enzymic binding sites. Incorporation of 3H,14C-labelledgeraniol into

1,8-cineole in a Rosmarinius sp. occurred without loss of tracer from C-1 of the
precursor, whereas nerol did lose tracer on similar cyclization. No plausible
explanation was offered for these observations,889 which invalidate the often
suggested proposal for redox-mediated conversion of geraniol into nerol prior to
cyclization to menthane and other alicyclic derivatives. Other evidence (cf. ref. 91 1)
also appears to refute the redox mechanism. Nevertheless the initial isomerization
appeared operative in Rosa spp. In flowerheads conversion of geraniol into nerol
involved loss of the pro-1S hydrogen, whereas the pro-1R atom was lost in the
reverse process (presumably catalysed by a different enzyme). NADPf-NADPHdependent cell-free extracts were also obtained that catalysed these processes. 890
The role of geraniol and nerol as precursors of cyclic monoterpenes is complicated
by the finding that linaloyl phosphate, linaloyl pyrophosphate, and linalool were
more highly incorporated than geraniol or nerol and their esters (both in vivo and
in cell-free extracts) into a-terpineol in a Mentha sp. and into limonene and perilla
aldehyde in Citrus and Perilla spp.891Thus linalool (or its biogenetic equivalent)
885
887
A. Akhila and D. V. Banthorpe, Phytochemistry, 1980, 19, 1429.

A. Akhila, D. V. Banthorpe, and M. G. Rowan, Phytochemistry, 1980, 19, 1433.
A. Akhila and D. V. Banthorpe, 2.Pflunzenphysiol., 1980, 99, 277.
A. Akhila and D. V. Banthorpe, Phytochemistry, 1980, 19, 1691.
F. Orsini and F. Pelizzoni, Gazz. Chim. Itul., 1980, 110, 553.
D. V. Banthorpe and I. Poots, Phytochemistry, 1979, 19, 1297.
T. Suga, T. Shishibori, and H. Morinaka, J . Chem. SOC.,Chem. Commun., 1980, 167.
Mono terpenoids
69
may be an obligatory intermediate en route from geraniol to cyclic monoterpenes, or

indeed may be directly formed by condensation of C, units. It has been long
known that the TPP- and DMAPP-derived moieties of monoterpenoids arise from
different metabolic pools in vivo, e.g. the former is very predominantly labelled by
MVA. It has now been demonstrated for a variety of terpene classesin several species
that co-feeding of MVA and leucine or valine resulted in the IPP-moiety being
derived from MVA whereas the DMAPP-derived unit was derived from the aminoacid. The former moiety was also labelled by [14C]alanine.892-894
Thiamine may be
(270a) R = CH=CMe,, R1= Me

(270b) R = CH,C6H4-p-OH, R1= Me
(272)
(271)
-6
O H
a coenzyme in the biosynthesis of certain monoterpenes. It was speculated (without,

hewever, any direct evidence) that thiamine adducts (270a,b; the former from
leucine) reacted nucleophilically with DMAPP (R1= Me) or geranyl pyrophosphate
[R1= (CH,),CH=CMe,] to give an artemisyl compound or bakuchiol (271)
respectively.895
[3H,14C]MVA was incorporated into la,2a,3p-trihydroxy-p-menthane by a
Fusicoccum sp., and the labelling pattern suggested that p-menth-Zen- 1-01 was
generated from an a-terpinyl cation by a 1,3-hydride shift, followed by formation
of the a-epoxide and cleavage.896 Ips beetles converted [2H]myrcene(the isotopically
normal substrate being obtained in nature from Pinus spp.) into ipsdienol and
K. Tange, T. Hirata, and T. Suga, Chem. Lett., 1979,269.
K. Tange, H. Okita, Y. Nakao, T. Hirata, and T. Suga, Chem. Lett., 1981, 777.
m4 K. Tange, Bull. Chem. SOC.
J., 1981, 54, 2763.
m5 G. E. Risinger, K. Karimian, S. Jungk, and J. B. Simpson, Experientia, 1978, 34, 1121.
eo6 G. Randazzo, A. Eridente, A. Boccalotte, and C. Rossi, Phytochemistry, 1981, 20, 2177.
epz
eOs
70
i p s i n 0 1 , ~and
~ ~ further studies have confirmed that ipsdienol is an obligatory
precursor of the
Geniposide may easily be chemically converted into
lO-hydro~yloganin,~~~
but neither the latter nor 7-epi- 10-hydroxyloganin (unlike
deoxyloganic acid or loganin) was a precursor of secologanin in Loniceru spp.SOO
In the course of studies on indole alkaloids it was demonstrated that the 10-0x0derivatives of geraniol and nerol were converted into secologanin in a Cuthmunthus
sp. 901 8-epi-Deoxyloganin was efficiently incorporated into lamiide and ipolamiide
in a Hebenstreitiu sp.9022H N.m.r. studies (one of few such applications to biosynthesis) showed that label at C-8 of deoxyloganin was retained during its
conversion into cornin (the 6-0x0-derivative) in a Verbena sp. This shows that
oxidation occurred at an unactivated position, i.e. there was no double bond at
C-7-C-8 in the immediate precursor of cornin. 903 Semburin (273) and isosemburin
(epimeric at the point of vinyl attachment) from a Swertiu sp. were the first 2,8dioxabicyclo[3.3.1Inonane derivatives encountered naturally : they were presumed
formed from sweroside (272).904 Biogenetic speculations have also been formulated
for details of the routes to A9- and A8-THCand cannabin01.~~~
The establishment of cell-free extracts that can sustain monoterpene synthesis has
always been difficult, but recently such systems have been developed, and this has
resulted in impressive conclusions concerning mechanistic and enzymatic details.
The main improvement in methodology, which, however, has not proved successful
in other hands, seems to be the use of very young plant material. This probably
eliminates many of the problems associated with tough cell walls and the presence of
phenolics that bedevil work with older tissue. However, extensive cultivation
schemes may be necessary to develop sufficient biomass for such studies. A preliminary characterization of bornyl pyrophosphate synthetase (MW cu. 95 000 dalton)
from a Sulviu sp. has been reported, and geranyl pyrophosphate (rather than the
neryl ester) was the preferred substrate. 906 A detailed proposed mechanism that
accommodates this choice of substrate and the formation of a pyrophosphate ester
(rather than an alcohol) involved formation (perhaps via linaloyl pyrophosphate)
and collapse (with bicyclization) of an intimate ion-pair comprising pyrophosphate
as the anionic component.
Extracts from the same plant contained separable
terpinyl phosphatases and pyrophosphatases : the latter type included a system
highly specific for bornyl pyrophosphate (the cleavage of which is essential for
camphor formation) together with one which preferentially accepted geranyl
pyrophosphate. The latter enzymic system has undoubtedly proved a source of
potential interference in studies on Cl0 cyclization processes.908 Another fraction
9069907
goo
Oo2
Oo3
Oa4
Oo5
Oo8
L. B. Hendry and six others, Nature, 1980, 284, 485.

R. H . Fish, L. E. Browne, D. L. Wood, and L. B. Hendry, Tetrahedron Lett., 1979, 1465.
K. Inoue, Y. Takeda, T. Tanahashi, and H. Inouye, Chem. Pharm. Bull., 1981, 29, 970.
K. Inoue, Y. Takeda, T. Tanahashi, and H. Inouye, Chem. Pharm. Bull., 1981, 29, 981.
A. R. Battersby, M. Thompson, K. H. Glusenkamp, and L. F. Tietze, Chem. Ber., 1981, 114,
3430.
S. Damtoft, J . Chem. SOC.,Chem. Commun., 1981, 228.
S. Damtoft, S. R. Jensen, and B. J. Nielsen, J . Chem. Soc., Chem. Commun., 1980, 42.
T. Sakai, H . Naoki, K. Takaki, and H. Kameoka, Chem. Lett., 1981, 1257.
C. E. Turner and M. A. Elsohly, J . Heterocycl. Chem., 1979, 16, 1667.
R. Croteau and F. Karp, Arch. Biochem. Biophys., 1979, 198, 512.
D. E. Cane, R. Iyengar, and M. S. Shiao, J . Am. Chem. Soc., 1981, 103, 914.
R. Croteau and F. Karp, Arch. Biochem. Biophys., 1979, 198, 523.
Monoterpenoids
71
from Salvia was worked up to a partially pure (MW ca. 91 000) dehydrogenase
that oxidized (+)-borne01 to (+)-camphor. It is possibly the same as a thujol
dehydrogenase extracted from a Tunucetum sp. 909 Another soluble enzyme from the
same source catalysed the conversion of geranyl pyrophosphate into a- and
p-pinenes, limonene, and camphene. Two cyclase preparations (MW 95 000 and
57 OOO) formed a-pinene, and both a-and p-pinenes respectively,910 It was shown that
the different preparations from SaZvia produced products of different structural
classes (a-pinene, camphene, borneol, limonene, 1,8-cineole) from [ 1 3H2,
U-14C]geranyl pyrophosphate without loss of 3H,and thus eliminated a mechanism
involving redox interconversion of geraniol and nerol in favour of a scheme
whereby the E-precursor was cyclized directly by way of a bonded linaloyl intermediate.g11The key enzymes for the conversion of geranyl pyrophosphate into
camphor in Salvia were at their highest levels of activity during the period of
maximum leaf expansion. This was held to indicate that immature leaves synthesized and accumulated camphor most rapidly,912but it may also reflect the ease
of extraction of the enzymes from these sources rather than from more mature
tissue. A soluble preparation from a Foeniculum sp. converted geranyl and neryl
pyrophosphates into fenchol and f e n ~ h o n e Unlike
. ~ ~ ~ the situation for borneol,
fenchyl pyrophosphate was not produced as a primary product and partial purification showed that the activities for the two percursors were coincident and presumably one enzyme was implicated for both. N o evidence was found (via isotope
dilution techniques) for a- or P-pinene or pinanols or their pyrophosphates as free
intermediates although the formation of fenchone was considered to involve the
generally accepted rearrangement of some pinane derivative. 914 Further fractionation gave a preparation (NADP+-dependent) that oxidized fenchol to fenchone,
and a similar preparation (for thujan-3-ol+thujone) was obtained from a Tanacetum sp. Specificity studies indicated that only a narrow range of monoterpenols
related to the structural classes produced in vivo were oxidized by these enzyme
systems.915
Time-course studies with 14C02showed that in a Thymus sp., y-terpinene was
converted into p-cymene and thymol in sequence,916and the appropriate y-terpinene
synthetase (MW ca. 96 000) was partially purified. Tracer studies indicated that
loss of a proton from C-5 of the a-terpinyl-like precursor to form the A*-unsaturation was accompanied, perhaps concertedly, by a 1,Zhydride shift from C-4
to C-8 to form y-terpinene. 917 Neomenthyl-p-D-glucoside was a major metabolite of
menthone in Mentha s p ~ . , and
~ l ~a cell-free extract also acetylated menthol.919
Detailed in vivo and in vitro investigations revealed that in leaf discs the bulk of the
neomenthol and menthol (produced from menthone) was converted into the glucoR. Croteau, C. L. Hooper, and M. Felton, Arch. Biochem. Biophys., 1978, 188, 182.
Gambliel and R. Croteau, Plant Physiol., 1980, 65, Suppl., 96.
Q1l R. Croteau and M. Felton, Arch. Biochem. Biophys., 1981, 207, 460.
Q12 R. Croteau, M. Felton, F. Karp, and R. Kjonaas, Plant Physiol., 1981, 67, 820.
Q13 R. Croteau, M. Felton, and R. C. Ronald, Arch. Biochem. Biophys., 1980, 200, 524.
@ l PR. Croteau, M. Felton, and R. C. Ronald, Arch. Biochem. Biophys., 1980, 200, 534.
@15 R. Croteau and N. M. Felton, Phytochemistry, 1980, 19, 1343.
Q16 A. J. Poulose and R. Croteau, Arch. Biochem. Biophys., 1978, 187, 307.
Q17 A. J. Poulose and R. Croteau, Arch. Biochem. Biophys., 1978, 191, 400.
Q18 R. Croteau and C. Martinkus, Plant Physiol., 1979, 64, 169.
Q19 R. Croteau and C. L. Hooper, Plant Physiol., 1978, 61, 737.
QOQ
@ l oH.
72
side and acetate respectively. This was not due to the specificity of the transferring
enzymes but was rather the result of the compartmentation of each stereospecific
dehydrogenase (forming menthol and neomenthol) with the appropriate unspecific
transferase. Indeed, a UDP-glucose : monoterpenol glucosyltransferase was partially
purified which accepted either ( +)-neomenthol or (-)-menthol as glucose
a c c e p t ~ rOther
. ~ ~ cell-free
~ ~ ~ ~extracts
~
from Mentha spp. reduced the Al- and A4double bonds of piperitenone, piperitone, and pulegone: at least five different
enzyme systems were implicated, specific for substrate and the stereochemistry of the
reduction. Treatment of the mint extracts with ion-exchange resins removed endogenous monoterpenes and thus made it possible to assay terpene interconversions by
quantitative g.c., without labelled substrates, and to identify the products by g.c.m.s.922 Cell-free extracts from a Chenopodiurn sp. catalysed the oxidation of
a-terpinene to ascaridole by singlet 0, and also the formation of allylic hydroperoxides from limonene. 923 Chemical studies have shown that hydrolysis of
geranyl pyrophosphate by Mn2+ seems a better model for enzymic reactions than
does acid hydrolysis.924
Tissue Cultures, Microbial Transformations.-Little success has rewarded the
search for cell cultures that effectively biosynthesize monoterpenes de now. The
most impressive studies utilize cultures from a variety of Mentha spp. : yields of oil
were some 60 (w/v) of those in the parent plants, but the monoterpene products
were generally more oxidized (i.e. ketones; extra C = C bonds predominated). In
vitro, oxidation at C-3 of the menthane skeleton was also restricted, apparently
owing to an inhibition of the enzymic reduction of the 4(8) double bond in the
intermediates formed.
Colchicine stimulated synthesis of essential oil by
Mentha cultures. 927 Iridoid glucosides have been produced by cultured cells of
Gardenia spp.673Menthone was biotransformed to neomenthol by Mentha suspension cultures,g28and Nicoriana lines oxidized linalool and its derivatives at C-10 to
aldehydes and alcohols,929and also foreign substrates such as a-terpineol (at C-6
and C-7) and trans-p-menthan-9-en- 1-01 (at C-4 and C- lo). 930
Monoterpenols were esterified by lipases from various micro-organisms
(especially Aspergillus ~pp.),~l
and (*)-caw1 acetates were hydrolysed by other
species to give chiral carveols together with (unreacted) acetates of the enanti~ m e r The
. ~ metabolic
~ ~
pathways for the conversions of (-)-carvone into (-)9259
R. Kyonaas, C. Martinkus-Taylor, and R. Croteau, Plant Physiol., 1980, 65, Suppl., 96.
C. Martinkus and R. Croteau, Plant Physiol., 1981, 68, 99.
9 2 2 A. J. Burbott and W. D. Loomis, Plant Physiol,, 1980, 65, Suppl., 96.
923 M. Johnson and R. Croteau, Plant Physiol., 1980, 65, Suppl., 96.
924 M. V. Vial and six others, Tetrahedron, 1981, 37, 2351.
s25 J. Bricout, M. J. Garcia-Rodriguez, C. Paupurdin, and R. Saussay, C . R. Hebd. Seances Acad.
Sci., Ser. D . , 1978, 287, 611.
826 C. Paupardin, Prod. Subst. Nut. Cult. In Vitro Tissue Cell. Veg., J . Etud., 1979, 119.
O Z 7 J. Bricout, M. J. Garcia-Rodriguez, and C. Paupurdin, C. R . Hebd. Seances Acad. Sci., Ser. D,
1978, 286, 1585.
928 D. Aviv, E. Krochmal, A. Dantes, and E. Galun, Planta Med., 1981, 42, 236.
T. Hirata, T. Aoki, Y. Hirano, I. Ito, and T. Suga, Bull. Chem. SOC.J., 1981, 54, 3527.
g30 T. Suga and six others, Chem. Lett., 1980, 229.
831 M. Iwai, S . Okumura, and Y. Tsujisaka, Agric. Biol. Chem., 1980, 44, 2731.
032 T. Oritani and K. Yamashita, Agric. Biol. Chem., 1980, 44, 2637.
820
Monoterpenoids
73
carveols and thence to dihydrocarveols in Streptomyces and Nocardia spp. have

been elucidated, 933 as have the microbial transformations of A1-THC.934 Anaerobic
bacteria growing on a-pinene as carbon source in simulated seawater conditions
yielded a pattern of G-C, hydrocarbons including toluene. 935
Chemotaxonomy.-Reports of monoterpenes produced by particular species and
genera are legion: most retread old paths or are of very limited significance. Some
notable work of real chemotaxonomic interest has, however, been reported concerning Pinus spp. 936-938 (including analyses of species resistant to bark beetles93g),
Abies ~ p p . , ~Juniperus
~O
spp.,941-943Tanacetum chemical races,61s and various
liverworts. 944-946 The chemotaxonomic significance of the distribution of acetylenic
r n o n ~ t e r p e n e and
s ~ ~ i~r i d o i d ~has
~ ~been
~ discussed.
Related studies record the change in monoterpene corporation during maturation
of Sequoia spp.949and the similar variations of menthol and its p-glucoside in
Mentha. 950 Hybridization experiments have shown that the occurrence of 60-90 %
pulegone in certain strains of Mentha spp. resulted from the lack of the genes
necessary to reduce this ketone to menthone or to oxidize it to m e n t h o f ~ r a n . ~ ~
A detailed genetic analysis of menthone-isomenthone production in Mentha spp.
has also been described. 95a
Metabolism, Biological Activity, Miscellaneous.-Camphene was converted into its
1,2-diol in rabbit,953and the pathways from a- and p-pinenes and car-3-ene to
hydroxylated, ring-opened, and decarboxylated compounds have been determined.954The 9,lO-oxide of THC was initially hydroxylated at C-8(p), and in the
side-chain byrat;g55 All-THC was hydroxylated at C-8, C-10, and in the side-chain
and subsequently epoxidized.956 The metabolism and degradation of various
Y. Noma, Agric. Biol. Chem., 1980, 44, 807.
M. Binder and A. Popp, Helv. Chim. Acta, 1980, 63, 2515.
s35 J. M. Hunt, R. J. Miller, and J. K. Whelan, Nature, 1980, 288, 577.
836 A. H. Conner, B. A. Nogasampagi, and J. W. Rowe, Phytochemistry, 1980, 19, 1121.
s37 E. Zavarin and K. Snajbark, J. Agric. Food Chem., 1980, 28, 829.
g38 E. N. Smit, V. A. Khan, T. D. Drebyschak, Z. V. Dubovenko, E. P. Kemertelidze, and V. A.
Pentegova, Khim. Prir. Soedin., 1981, 81, 665.
93s L. Gollob, Naturwissenschaften, 1980, 67,409.
940 A. Roedam, J. J. C. Scheffer, and A. B. Svendsen, J. Agric. Food. Chem., 1980, 28,862.
g41 E. von Rudloff, L. Hogge, and M. Granat, Phytochemistry, 1980, 19, 1701.
g42 R. P. Adams, E. von Rudloff, and L. Hogge, Lloydia, 1981, 44, 21.
s43 R. P. Adams, M. M. Palma, and W. S. Moore, Phytochemistry, 1981, 20, 2501.
s44 Y. Asakawa, R. Matsuda, and T. Takernoto, Phytochemistry, 1980, 19, 567.
s45 Y. Asakawa, R. Matsuda, M. Toyota, S. Hattori, and G. Ourisson, Phytochemistry, 1981,20,
@34
2187.
946
g47
s48
g4s
s50
951
OSa
s53
s54
g55
g56
Y. Asakawa, M. Toyota, T. Takernoto, and R. Mues, Phytochemistry, 1981, 20, 2695.

F. Bohlmann, H. Robinson, and R. M. King, Phytochemistry, 1980, 19, 2235.
D. Corrigan, R. F. Tirnoney, and D. M. X. Donnelly, Phytochemistry, 1978, 17, 1131.
K. A. Okamoto, B. 0. Ellison, and R. E. Kepner, J. Agric. Food Chem., 1981, 29, 324.
J. Sakata and K. Koshimizu, Nippon Nogei Kagaku Kaishi, 1980, 54, 1037.
D. E. Lincoln and M. J. Murray, Phytochemistry, 1978, 17, 1727.
M. J. Murray, D. E. Lincoln, and F. W. Hefendehl, Phytochemistry, 1980, 19,2103.
T. Ishida, Y.Asakawa, T. Takamoto, and T. Aratani, J. Pharm. Sci., 1979, 68,928.
T. Ishida, Y. Asakawa, T. Takamoto, and T. Aratani, J. Pharm. Sci., 1981, 70,406.
A. Ohlsson and I. Emanuelson, Acta Pharm. Suec., 1979, 16, 396,
M. Binder and U. Barlage, Helv. Chim. Acta, 1980, 63, 255.
74
pyrethroids in insects has been fully worked out. 957 Chemical and ultrastructural
investigation of a Pinus species implied that the monoterpenes and other resin
components were terminal products of metabolism and were not degraded during
normal growth or starvation conditions. 958 This appears to be in contradiction to
previous studies on terpenoid metabolism.
Several pairs of cannabinoid isomers were synthesized and tested for biological
activity: two requirements were elucidated: (a) in the absence of other substituents,
the equatorial stereochemistry of substituents at C-9 determined activity and
(b) pairs of compounds with groups at C-9 and C-10, or C-8 and C-9, had the same
activity if the configurations (a or p) at the appropriate carbons were the same.959
The antifungal activity of monoterpene aldehydesg60and the metabolism of monoterpenes in mammals leading to acute poisoning by pine oil have been described.961
The effects of light on pinene synthesis in Pinus s ~ p .chloroplast
, ~ ~ ~ autonomy in the
formation of acetyl coenzyme A and in terpenoid b i o s y n t h e ~ i sterpene
, ~ ~ ~ formation
by
and the influence of metachlor on growth and terpenoid synthesis
have been i r ~ v e s t i g a t e d . ~ ~ ~
We thank Dr. Margaret Banthorpe for much help with the preparation of this
report.
*57
a58
959
g60
g61
g62
g64
866
L. 0. RUZO,L. C. Gaughan, and J. E. Casida, Pestic. Biochem. Physiol., 1981, 15, 137.
J. Benayoun and R. Ikan, Ann. Bot., 1980, 45, 645.
R. Mechoulam and seven others, J . Med. Chem., 1980, 23, 1068.
N. Kurita, M. Miyaji, R. Kurane, Y. Takahara, and K. Ichimura, Agric. Biol. Chem., 1979,43,
2365.
C. Koppel, J. Tenczer, U. Tonnesmann, T. Schikop, and K. Ibe, Arch. Toxicol., 1981, 49, 73.
M. Gleizes, G. Pauly, C. Bernard-Dagan,and R. Jacques, Physiol. Plant., 1980, 50, 16.
K. Grumbach and B. Forn, 2. Nuturforsch., Teil C, 1980, 35, 645.
G. D. Prestwich, R. W. Sowes, and M. S. Collins, Insect Biochem., 1981, 11, 331.
R. E. Wilkinson, Pestic. Biochem. Physiol., 1981, 16, 63.
2
Sesquiterpenoids
BY J.
s. ROBERTS
1 Farnesane
An investigation of the nudibranch, Chromodoris marislae, has led to the identification of marislin (la) together with the minor constituents (2a,b) and (3a,b).l
Acid or heat treatment of marislin brings about its conversion into pleraplysillin-2
(1b), a sponge metabolite of Mediterranean origin. Pleraplysillin-2 (1b) has been
synthesized by coupling 4-methyl-2-furyl-lithium with the bromo-geraniol derivative
(4) followed by deprotection, oxidative esterification, hydrolysis, and final esterification with 3-f~rylmethanol.~
Further work on the constituents of Eremophila
Br
(4)
rotundijdia has led to the isolation of ( 5 ) and 4-hydroxydendrolasin (6).3 The diene
(5) can be obtained by cyclodehydration of the alcohols derived from reduction of
dihydrophymaspermone (7). Other new farnesyl/nerolidyl sesquiterpenoids include
vernopolyanthone (8) and vernopolyanthofuran (9) (from various Vernonia
species),* 3E- and 2-semistriatin methyl ether (I 0),5 and 5-hydroxynerolidol (1 1)
(together with its 5-a~etate).~
The stereoselective synthesis of P-sinensal (14) has been achieved by reaction
of the x-allylnickel(1I) complex (12) (derived from brornomyrcene) with the chloroa
a
4
J. E. Hochlowski and D. J. Faulkner, Tetrahedron Lett., 1981, 22, 271.

D. W. Knight and D. C. Rustidge, J . Chem. Soc., Perkin Trans. 1, 1981, 679.
E. Dimitriadis and R. A. Massy-Westropp, Aust. J. Chem., 1980, 33, 2729.
F. Bohlmann, J. Jakupovic, R. K. Gupta, R. M. King, and H. Robinson, Phytochemistry, 1981,
20,473.
F. Bohlmann, W.-R. Abraham, H. Robinson, and R. M. King, Phytochernistry, 1981,20,1639.
F . Bohlmann, C. Zdero, R. M. King, and H. Robinson, Phytochernistry, 1981, 20, 1643.
75
76
cq..&&
/
/
/
OMe
OAng
(1 1)
acetal (13) followed by acid hydr~lysis.~

Full details of the synthesis of 7-hydroxymyoporone (15) have been published.
In two important papers Poulter et al. have published their results on the
compelling evidence for a stepwise mechanism for the 1 -4 condensation reaction
between isopentenyl pyrophosphate and geranyl pyrophosphate to form farnesyl
(15)
pyrophosphate (Scheme 1). In the first paper9 evidence is presented for a geranyl
cation-pyrophosphate ion pair which is enzyme bound, i.e. ionization of geranyl
pyrophosphate and condensation with isopentenyl pyrophosphate are not concerted. In the second communication,1 ls0-labelling studies have shown that
K. Sato, S . Inoue, and K. Watanabe, J . Chem. SOC.,Perkin Trans, 1, 1981, 2411.
lo
H. J. Reich, S . K. Shah, P. M. Gold, and R. E. Olson, J . Am. Chem. SOC.,1981, 103, 3112.
C. D. Poulter, P. L. Wiggins, and A. T. Le, J . Am. Chem. SOC.,1981, 103, 3926; see also M.
Ladika, I. Bregovec, and D. E. Sunko, J . Am. Chem. SOC.,1981, 103, 1285, 7797; for an
excellent review of prenyl transferases and isomerase, see C. D. Poulter and H. C. Rilling,
Biosynthesis of Isoprenoid Compounds, Vol. 1, ed. J. W. Porter and S . L. Spurgeon, John
Wiley, New York, 1981, p. 161.
E. A. Mash, G. M. Gurria, and C . D. Poulter, J . Am. Chem. Soc., 1981, 103, 3927.
Sesquiterpenoids
77
Scheme 1
the geranyl cation-pyrophosphate ion pair has a rigid structure and does not
scramble the bridging oxygen atom with the two non-bridging oxygen atoms in the
pyrophosphate counter-ion.
Four components of the trail pheromone of the red imported fire ant, Solenopsis
invicta, have been identified as 2,E-a-farnesene (16) E,E-a-farnesene (17), and
the two homofarnesenes (1 8) and (1 9).11 In a related study12all of the eight possible
diastereoisomers of do-farnesene (20) have been synthesized. In this paper it is
claimed that the E,Z,Z-isomer is identical to material isolated from the Dufours
glands of S. invicta. Faranal (21) a trail pheromone of the pharaoh ant has been
synthesized by small scale enzymatic condensation of 2-3-methylpent-3-enyl
pyrophosphate (23) with homogeranyl pyrophosphate (22) to give the 4R-triene
(24).13 Alkaline hydrolysis of the pyrophosphiite ester followed by manganese
dioxide oxidation gave the corresponding a, P-unsaturated aldehyde. Reduction of
this aldehyde with triethylsilane in the presence of (Ph3P),RhCl gave both the
3S,4R and 3R,4R diastereoisomers and it was shown by bioassay that the former (21)
corresponds to the natural pheromone. Three other syntheses14-16of faranal using
relatively straightforward synthetic procedures have been recorded ; one of these14
produces faranal in optically active form.
An interesting review of the biosynthesis and transport of juvenile hormones iri
insects has appeared.17The syntheses of the juvenile hormones JHI-JHIII (25)-
l1
l2
I4
l5
l6
R. K. Vander Meer, F. D. Williams, and C. S. Lofgren, Tetrahedron Lett., 1981, 22, 1651.
H. J. Williams, M. R. Strand, and S. B. Vinson, Tetrahedron, 1981, 37, 2763.
M. Kobayashi, T. Koyama, K. Ogura, S. Seto, F. J. Ritter, and I. E. M. Bruggemann-Rotgans,
J. Am. Chem. SOC.,1980, 102,6602.
K. Mori and H. Ueda, Tetrahedron Lett., 1981, 22,461.
D. W. Knight and B. Ojhara, Tetrahedron Lett., 1981, 22, 5101.
R. Baker, D. C. Billington, and N. Ekanayake, J . Chem. SOC.,Chem. Commun., 1981, 1234.
S. J. Kramer and J. H. Law, Acc. Chem. Res., 1980, 13, 297.
78
(27) together with a number of analogues have been achieved by the use of vinylcuprates as key intermediates.18
1"
(16) R
(18) R
H
Me
x
(25) R' = R2 = Et
(26) R1= Et, R2 = Me
(27) R1 = R2 = Me
2 Mono- and Bi-cyclofarnesane

The search for marine metabolites with biological activity continues to produce
new and interesting compounds. These include siphonodictyal-A (28) and siphonodictyal-B (29) which have been isolated from the limestone-burrowing sponge,
Siphonodictyon c~ralliphagurn.~~
The green alga, Caulerpa Jlexilis, has been shown
to contain the two monocyclic sesquiterpenoids (30) and (31);20 their derivation
from the acyclic precursor flexilin (32) which had previously been isolated
from C. pexilis seems highly probable. Previous work on the red alga, Laurencia
filiforrnis, has demonstrated the presence of laurane, eudesmane, and chamigrane
sesquiterpenoids. In a study21of another variety of this alga from Western Australia,
aplysistatin (33),22 previously obtained from the sea-hare Aplysia angasi, and
2o
21
22
H. KIeijn, H. Westmijze, and P. Vermeer, J . Roy. Netherlands Chem. SOC.,1981, 100, 249.
B. Sullivan, P. Djura, D. E. McIntyre, and D. J . Faulkner, Tetrahedron, 1981, 37, 979.
R. J. Capon, E. L. Ghisalberti, and P. R. Jefferies, Aust. J . Chem., 1981, 34, 1775.
R. Capon, E. L. Ghisalberti, P. R. Jefferies, B. W. Skelton, and A. H. White, Tetrahedron,
1981,37, 1613.
R. B. Von Dreele and J. P. Y . Kao, Acta Cryst., 1980, B36, 2695.
79
Sesquiterpenoids
CHO
AcO
(30)
woAc
(33) R
(34) R
=
=
H
OH
6p-hydroxyaplysistatin (34)have been isolated and their structures determined by

X-ray analysis. The digestive glands of the nudibranch, Dendrodoris limbata,
contain sesquiterpenoids of the type (35) in which the R group is a saturated,
mono-unsaturated, or di-unsaturated fatty-acid chain (c16 and C,, are the most
abundant species).23Nakafuran-8 (37) and nakafuran-9 (38) are two novel sesquiterpenoids which have been isolated from three sources, namely the marine
sponge Dysidea fragilis and its prey, the two nudibranchs, Hypselodorisgodefroyana
and Chromodoris rnaridadil~s.~~
The biogenesis of these two compounds is considered to be in terms of derivation from the microcionins (36) as shown in Scheme 2.
The bromonium ion-initiated cyclization of acyclic precursors as a biomimetic
route to certain marine metabolites continues to be an attractive method of
synthesizing such compounds. Thus, treatment of nerolidol with 2,4,4,6-tetrabromocyclohexa-2,5-dione gave in low yield a- and p-snyderols (39) and (40),
together with the two 3p-bromocaparrapi oxides (41) (epimeric at C-8) of which
the 8a-methyl isomer is the naturally occuring
A higher yielding
synthesis of a- and p-snyderols involves acid-catalysed cyclization of the terminal
bromohydrin of homogeranonitrile (43)to give the isomeric nitriles (44).26Treatment of (44)with methyl-lithium followed by a Grignard reaction of the derived
23
24
25
26
G. Cimino, S. De Rosa, S. De Stefano, and G . Sodano, Tetrahedron Lett., 1981, 22, 1271.
G. Schulte, P. J. Scheuer, and 0. J. McConnell, Helv. Chim. Acta, 1980, 63, 2159.
T. Kato, K. Ishii, I. Ichinose, Y. Nakai, and T. Kumagai, J . Chem. SOC.,Chem. Commun.,
1980, 1106.
A. Murai, A. Abiko, K. Kato, and T. Masamune, Chem. Lett., 1981, 1125.
80
(37)
Scheme 2
methylketones with vinylmagnesium bromide produced cr-(39) and p-snyderol(40).

In a related experiment phenylselenium anion opening of the terrninal epoxide of
neroiidol produced the P-hydroxy-selenide (45) which, on treatment with acid
followed by deselenation with tri-n-butyltin hydride, gave the two caparrapi
oxides (42) (epimeric at C-8).27A new sesquiterpenoid from the red alga Laurencia
obtusa is obtusenol (46).2*This dibromide has been synthesized by reaction of
trans,trans-farnesol acetate with aqueous NBS to give (47) as one of the
Br
Br
OH
OH
(41) R
(42) R
(39)
Br
W
N
HO
Br
(46)
2'
28
29
J;);""
Br
=
=
Br
H
PhSe
HO
Br
(47)
T. Kametani, K . Fukumoto, H. Kurobe, and H . Nemoto, Tetrahedron Lett., 1981, 22, 3653.
S. Imre, S. Islimyeli, A. OztunG, and R. H . Thornson, Phytochemistry, 1981,20,833.
A. G . Gonzalez, J . D. Martin, C. Perez, M. A. Ramirez, and F. Ravelo, Tetrahedron Lett.,
1981,22, 5071.
81
Sesquiterpenoids
(51)
(50)
This compound must arise from bromonium ion cyclization of the 6,7-bromohydrin
of farnesol acetate. Hydrolysis of the acetate group in (47) and sequential treatment
with phosphorus tribromide and water gave obtusenol (46). Other syntheses of
marine sesquiterpenoids include those of pallescensin-E (48),30furoventalene (49),31
and dactyloxene-B (50) and -C(51).32 The last mentioned established the absolute
configurations of the two dactyloxenes. A second synthesis of ancistrofuran (53) and
its C-2epimer has been recorded starting from the lactone (52)which is derived
from homogeranic acid (Scheme 3).33
Ph,PQ
w
H
h i , iii
w02w0
H
(53)
Reagents: i, Bu',AIH; ii, PhSeCI; iii, Ac0,H; iv, H 4
Scheme 3
The diverse biological activity (e.g. insect antifeeding, plant growth regulation,
molluscicidal) of a number of drimane sesquiterpenoids has stimulated considerable interest in their synthesis and the year under review has seen many
new developments and improvements. Much of the synthetic work has centred
around the key bicyclic diester (54) derived from l-vinyl-2,6,6-trimethylcyclohexene
and dimethyl acetylenedicarboxylate. In contrast to earlier
Ley et ~ 2 1 . ~ ~
30
31
32
33
34
35
R. Baker and R. J. Sims, Tetrahedron Lett., 1981, 22, 161.

F. Kido, Y. Noda, T. Maruyama, C. Kabuto, and A. Yoshikoshi, J . Org. Chem., 1981,46,4264.
B. Maurer, A. Hauser, and G. Ohloff, Helv. Chim. A d a , 1980, 63, 2503.
T. R. Hoye and A. J. Caruso, J. Org. Chem., 1981,46, 1198.
S. P. Tanis and K. Nakanishi, J . Am. Chem. SOC.,1979, 101, 4398.
S. C. Howell, S. V. Ley, M. Mahon, and P. A. Worthington, J . Chem. SOC.,Chem. Commun.,
1981, 507.
82
have shown that hydrogenation of (54) under isomerizing conditions (trace of HCl)
gives the trans-fused decalin derivative (55). This finding has paved the way to
short and efficient syntheses of cinnamolide (56), polygodial(57), and warburganal
(58) (Scheme 4).36Lallemand and c o - w ~ r k e r shave
~ ~ also used the diester (54) as
the starting material for the syntheses of polygodial (57) and drimenin (60).
They found that deprotonation of (54) with LDA followed by kinetic protonation
at low temperature gives the isomerized diester (59). Normal catalytic hydrogenation
of (59) gives the key compound ( 5 5 ) which was converted into polygodial (57)
C0,Me
CO,Me
C0,Me
ix, x
/;"
'
'
(jy
H
(55)
qO,Me
/,vi
OAc
(56)
OH
...
Vlll
+
& HH
@
H
Ho
(58)
Reagents: i, H,-Pd/C; ii, LiAlH,; iii, Ag,CO,-celite; iv, Me, SO-(COCl),, then NEt3; v, Ac,Opy; vi, SeO,; vii, K,CO,-MeOH; viii, Me,SO-TFAA, then NEt3; ix, Bu',AlH; x, PTSA;
xi, LDA; xii, H +
Scheme 4
36
S. V. Ley and M. Mahon, Tetrahedron Lett., 1981, 22, 3909.

M. Jallali-Naini, G. Boussac, P. Lemaitre, M. Larcheveque, D. Guillerm, and J.-Y. Lallemand,
Tetrahedron Lett., 1981, 22, 2995.
Sesquiterpenoids
a3
(OH
pH
...
Vlll
ix
+
OH
&OACH O
liv
&*Me
xi
f-
H O
#OACH O
.1
vii, xii, xiii
(63)
liv
(62)
Reagents: i, BH,-THF; ii, H,O,OH-; iii, MsC1-py; iv, DBU; v, LiAlH,, vi, H,-Pd/C;
vii, Bu',AIH; viii, PCC; ix, Pb (OAc),; x, MCPBA; xi, MeOH-H+; xii, H 3 0 + ;xiii, Ac,O-pyDMAP
Scheme 5
by an exactly parallel method to that described by Ley et aE. Selective reduction of

(55) followed by lactonization gives drimenin (60) (Scheme 4). Burton and White3*
have also used the diester (54) as the starting point for syntheses of isodrimenin (61),
fragrolide (62), and cinnamodial(63) (Scheme 5). Euryfuran (65), valdiviolide (66),
and confertifolin (67) have all been synthesized from the trans-decalone (64)
(Scheme 6).39A rather different approach to the drimane sesquiterpenoids is seen in
the synthesis of confertifolin (67) by an interesting degradation of the diterpene
manool (68) (Scheme 7).40The key steps in this synthesis are the Norrish type I1
38
as
40
L. P. J. Burton and J. D. White, J. Am. Chem. SOC.,1981, 103, 3226.

S. V. Ley and M. Mahon, Tetrahedron Lett., 1981, 22,4747.
T. Nakano and M. A. Maillo, Synth. Commun., 1981, 11,463.
84
iiii
(66)
Reagents: i, HC0,Et-NaH; ii, BUSH-PTSA; iii, Me,S-CH,;

eosin-2,6-lutidine; vi, Br,-MeOH; vii, H,O+
iv, A or HgS04; v, O&v-
Scheme 6
f--iii
(67)
Reagents: i, KMnO,; ii, h v ; iii,
hv,
(70)
02-Rose Bengal
Scheme 7
Sesquiterpenoids
85
cleavage of the ketone (69) and the unusual photo-oxygenation of the diene (70) to
give confertifolin (67) directly. Full details and further refinements of the syntheses
of isodrimenin (6 I), confertifolin (67),41and warburganal (58)42 have been published.
Norambreinolide (71) has been synthesized by stannic chloride-promoted cycliza-
tion of trans-P-monocyclohomofarnesic acid (72) which is derived from dihydro-pi ~ n o n eAnother

. ~ ~ ambergris compound, a-ambrinol(73) can be obtained in a short
synthesis from 3-methyl-2-cyclohexenone (Scheme 8).44
New drimane sesquiterpenoids include 6p-acetoxyisodrimenin (74), capsicodendrin, a partially characterized tetramer of cinnamodial (63),45 albicanyl
3,4-dihydroxycinnamate (75), albicanyl 2,4-dihydroxycinnamate (76) (both
liverwort c ~ n s t i t u e n t s ) , and
~ ~ polyveoline (77), an indolo~esquiterpenoid.4~
Full details of the isolation and structural determination of pebrolide (78) and
its congeners (79) and (80) have been published.48The biosynthesis of pebrolide
Jiv, v
n
Reagents: i, MeMgI-CuI; ii, Me3SiC1; iii,
v, H 3 0 +
(73)
-TiC14-Ti(OPri)4; iv, Ph,P==CH,;
Scheme 8
42
4a
44
46
H. Akita, T. Naito, and T. Oishi, Chem. Pharm. Bull., 1980, 28, 2166.
T. Nakata, H. Akita, T. Naito, and T. Oishi, Chem. Pharm. Bull., 1980, 28, 2172.
A. Saito, H. Matsushita, Y. Tsujino, and H. Kaneko, Chem. Lett., 1981, 757.
0. Takazawa, H. Tamura, K. Kogami, and K. Hayashi, Chem. Lett., 1980, 1257.
I. I. Mahmoud, A. D. Kinghorn, G. A. Cordell, and N. R. Farnsworth, J. Nat. Products, 1980,
43, 365.
1e
47
48
M. Toyota, Y. Asakawa, and T. Takemoto, Phytochemistry, 1981, 20, 2359.

R. Hocquemiller, G. Dubois, M. Leboeuf, A. Cave, N. Kunesch, C. Riche, and A. Chiaroni,
N. J. McCorkindale, C. H. Calzadilla, S. A. Hutchinson, D. H. Kitson, G. Ferguson, and
I. M. Campbell, Tetrahedron, 1981, 37, 649.
86
&
H OAc
(74)
(75) R1= H, R2 = OH
(76) R = OH, R2 = H
@$
,. H
OCOPh
HO
i 2
(77)
(78) R = OH, R2= OAC

(79) R = R2 = OH
(80) R = H, R2 = OAC
has also been investigated using [2-14C,2-3H2]mevalonicacid and degradative

studies indicate the expected labelling pattern based on cyclization of farnesyl
pyroph~sphate.~~
The antifungal mould metabolite siccanin (8 1) has been synthesized in nineteen
The asymmetric intramolecular Diels-Alder reaction of the magnesium
salt of the amide (82) gives a predominance of the tricyclic diastereoisomer (83)
which can be converted into the enantiomer (84) of naturally occurring farnesiferol C.51
Some very interesting biosynthetic studies have been carried out by Simpson
and co-workers on the meroterpenoids austin (86),52 terretonin (87),53anditomin
8WNqwp
.
..._
fl
(82)
HO
OOH
(83)
(81)
(84)
48
61
b2
63
N. J. McCorkindale, C. H . Calzadilla, and R. L. Baxter, Tetrahedron, 1981, 37, 1991.

M. Kato, K . Heima, Y . Matsumura, and A. Yoshikoshi, J . Am. Chem. SOC.,
1981, 103, 2434.
T. Mukaiyama and N. Iwasawa, Chem. Lett., 1981, 29.
T. J. Simpson and D. J. StenzeI, J . Chem. SOC.,
Chem. Commun., 1981, 1042.
C . H. McIntyre and T. J. Simpson, J . Chem. SOC.,Chem. Commun., 1981, 1043.
Sesguiterpenoids
87
(88)754v55and andilesin C (89).54 Incorporation of 13C-labels indicate that the biosyntheses of these compounds can be rationalized in terms of alkylation of farnesll
pyrophosphate by a bis-C-methylated tetraketide-derived phenolic precursor to
produce the key intermediate (85). Cyclization followed by a series of rearrangements and oxidative modifications leads to these interesting metabolites. The
efficient incorporation of ethyl 2,4-dihydroxy-3,5,6-trimethylbenzoate (90) and
0
C02Me
(88)
6;
C02Et
(90) R = OH
(91) R = H
(91) demonstrates that biological Cethyl 4-hydroxy-2,3,5-trimethylbenzoate
methylation by methionine precedes aromatization of the tetraketide.56 Simpson
(92) R
(93) R
54
65
56
OH
OH
(94)
T. J. Simpson, Tetrahedron Lett., 1981, 22, 3785.

T. J. Simpson and M. D. Walkinshaw, J . Chem. SOC.,Chem. Commun., 1981, 914.
A. J. Bartlett, J . S. E. Holker, E. OBrien, and T. J. Simpson, J . Chem. SOC.,Chem. Commun.,
1981, 1198.
88
et uL5' have also found that a mutant of the andibenin producing strain of Aspergillus vuriecolor which lacks the polyketide-derived mycelial pigments produces the
two drimane sesquiterpenoids astellolide A (92) and B (93) which are structurally
close to the pebrolides (78)-(80).
A very complete account has been published5* of the excellent labelling studies
which have been carried out to elucidate cyclonerodiol (94) biosynthesis and the
enzymatic conversion of farnesyl pyrophosphate into nerolidyl pyrophosphate
(Vol. 10, pp. 5-7).
3 Bisabolane
New bisabolane sesquiterpenoids from a variety of plant sources include (95)( 102).59-64E-y-Bisabolene-8,9-epoxide(1 03) has been isolated from the alga
Laurenciu n i p p o n i ~ aThis
. ~ ~ compound is possibly the precursor of various halogenated chamigranes which are abundant in Laurencia algae.
Q
$, . ,A
@
,n-
F Ang
pcH
(9359
(9Q5'
(97y0
P
R
(98)''
I
\
(99y2
(100)'3
(101)s4R
(102) R
CH,OAc
CHO
A low yield synthesis of p-bisabolene (104) has been achieved by reaction of

(+)-limonene with acetic acid and acetic anhydride in the presence of manganese
(111) acetate to give the acid (105) which could be converted into p-bisabolene in
R. 0. Gould, T. J. Simpson, and M. D. Walkinshaw, Tetrahedron Lett., 1981, 22, 1047.
D. E. Cane, R. Iyengar, and M.-S. Shiao, J . Am. Chem. Sac., 1981, 103,914; for an excellent
review of the biosynthesis of sesquiterpenes see D. E. Cane, 'Biosynthesis of Isoprenoid
Compounds', Vol. 1, ed. J. W. Porter and S . L. Spurgeon, John Wiley, New York, 1981, p. 283.
6 9 F. Bohlmann and J. Ziesche, Phytochemistry, 1981, 20, 469.
Eo F. Bohlmann, M. Grenz, R. K. Gupta, A. K. Dhar, M . Ahmed, R. M . King, and H. Robinson,
Phytochemistry, 1980 19, 2391.
F. Bohlmann, A. Suwita, H. Robinson, and R. M. King, Phytochemistry, 1981, 20, 1887.
62 A. Rustaiyan, M. Dabiri, R. K. Gupta, and F. Bohlmann, Phytochemistry, 1981,20, 1429.
Es F. Bohlmann, C. Zdero, H. Robinson, and R. M. King, Phytochemistry, 1981, 20, 2245.
E4 F. Bohlmann, C. Zdero, R. M. King, and H. Robinson, Phytochemistry, 1981, 20, 2389.
m T. Suzuki, H . Kikuchi, and E. Kurosawa, Chem. Lett., 1980, 1267.
67
68
89
Sesquiterpenoids
p Hpp
R
(108)
(109) R = CHO
(1 10) R = CH20H
three steps.6sAnother synthesis of p-bisabolene involves the Carroll reaction of the

keto-ester (106) with 2-methyl-3-buten-2-01 in the presence of aluminium isopropoxide to give the ketone (107) followed by methylenati~n.~'
A simple synthesis of
( +)-a-bisabolol (108) and its C-8 epimer involves prenylation of ( +)-limonene
with 2-methyl-3-buten-2-01in the presence of formic acid followed by hydrolysis of
the derived formates.68A similar reaction with (-)-limonene gives the two enantiomeric bisabolols of which the (-)-a-isomer is a naturally occurring compound.
Short syntheses of nuciferal(109)69and E-nuciferol(1
have also been recorded.
4 Sesquicamphane, Sesquipinane
Two additional minor components of East Indian sandalwood oil have been
identified as trans-p-santalol(ll1) (cf. Vol 11, ref. 48) and epi-cis-p-santalol(112).71
New syntheses in this area include those of cis-p-santalol (1 13) (Scheme 9),72
68
67
6s
70
72
N. Fukamiya, M. Oki, M. Okano, and T. Aratani, Chem. Ind., 1981, 96.

T.-L. Ho, Synth. Commun., 1981, 11, 237.
D. Babin, J.-D. Fourneron, and M. Julia, Tetrahedron, 1981, 37, Supplement No. 1, 1.
L. Blanco, N. Slougui, G. Rousseau, and J. M. Conia, Tetrahedron Lett., 1981, 22, 645,
J.-C.Depezay and Y. Le Merrer, Bull. Chim. SOC.France, 1981, 11-306.
P.A. Christenson, N. Secord, and B. J. Willis, Phytochemistry, 1981, 20, 1139.
K. Sato, 0. Miyamoto, S. Inoue, and K. Honda, Chem. Lett., 1981, 1183.
90
(1 13)
Reagents: i, LDA; ii,
; iii, Bu',AlH; iv, PBr,; v, LiAIH,
Br TOAc
Scheme 9
1 vii
p,
I
xii, v, vi
OSiMe,But
\viii,
ix
ii, xii
Aii-xv
Y*
xvii
(1 12)
(115)
(112)
Reagents: i, A ; ii, H30+; iii, Ph,P=CMe,; iv, CrO,.py; v, NaNH,; vi, MeI; vii, Zn-TiC1,CH,Br,; viii, NMO-OSO,; ix, NaIO,; x, LiAlH,; xi, C1SiMe2Bu'-imidazole; xii, PCC;
xiii, PPh,=CHMe; xiv, BuLi ; xv, CH,O ; xvi, (EtO),POC(Me)==CO,Et ; xvii, AlH,
Scheme 10
Sesquiterpenoids
CO2H
111I
& &
+
ii, iii
--L
'
91
C02H
OH
Jiv
(116)
Reagents: i, A; ii, Ra-Ni; iii, LiAlH,; iv, E u - H g ( O A c ) , , 135 "C;v, LiAlH,-AlCl,
Scheme 11
epi-p-santalene (1 14), epi-cis-p-santalol (1 12), epi-trans-P-santalol (1 15) (Scheme

and p-santalene (1 16) (Scheme 1l).74A low yield synthesis of p-santalene (1 16)
is realized in the final step of the last synthesis.
The novel sesquiterpenoid, heterocurvistone (1 17) which belongs to the sesquicamphane group, has been isolated from the plant Heterotropa curvistigma.75
Its 2-oxabicyclo[2,2,2]octylskeleton bears a close resemblance to the monoterpene,

cineole (118). The unique sesquiterpene albene (1 19) has been synthesized for a
second time (Scheme 12).76
73
R. L. Snowden, P. Sonnay, and G. Ohloff, Helv. Chim. Acta, 1981, 64, 25
'' F.-M.Simmross and P. Weyerstahl, Liebigs Ann. Chem., 1981, 1089.

7s
76
M. Niwa, Y. Sugie, and S. Yamamura, Phytochemistry, 1981; 20, 11 37.

J. E. Baldwin and T. C. Barden, J . Org. Chem., 1981, 46, 2442.
92
Reagents: i, MeLi; ii,
-PTSA; iii, Bu',AlH; iv, KOH; v, Ac,O-NaOAc; vi, Li-EtNH,
Scheme 12
5 Cuparane, Herbertane, Laurane, Trichothecane

The direct geminal dimethylation of ketones using dimethyltitanium dichloride
has provided an extremely simple synthesis of cuparene (120) from the ketone
(l2l)." This efficient procedure should prove useful in other sesquiterpenoid
syntheses in view of the fact that the gern-dimethyl group is a common feature in a
number of such compounds. A new sesquiterpene, (-)-herbertene (122), has been
(120)
(121)
(122)
isolated from the liverwort Herberta a d ~ n c aIn. ~view
~ o f the fact that (-)-cuparene
is a known liverwort constituent, the genesis of herbertene by a 1,2-methyl migration
of a cuparene-type precursor seems reasonable. Caraibical (123) has been isolated
from the red algal species Laurencia caraibica and it is closely related to the bicyclic
compound (124) found in the same alga.79
Intense interest in the trichothecane sesquiterpenoids has continued unabated
on two fronts. The first concerns the conflicting reportsso of the possible use of
mycotoxins of this class of sesquiterpenoid as fungal warfare agents ('yellow rain')
in Kampuchea and Laos. The second area of research centres around the total
synthesis of trichothecane sesquiterpenoids, although it should be pointed out that
phase TI clinical trials with anguidine (125) as an antitumour drug appear to be
disappointings1 thus possibly taking the edge off the synthetic impetus.
77
'I3
7s
8o
M. T. Reetz, J. Westermann, and R. Steinbach, J. Chem. Sac., Chem. Commun., 1981, 237.
A. Matsuo, S. Yuki, M. Nakayama, and S. Hayashi, J. Chem. SOC.,Chem. Commun., 1981,864.
R. R. Izac, J. S. Drage, and J. J. Sirns, Tetrahedron Lett., 1981, 22, 1799.
Chem. Eng. News, 1981, Sept.21, p. 7; Oct. 26, p. 15; Nov. 16, p. 10; Dec. 14, p. 21.
Chem. Eng. News, 1981, Nov. 30, p. 29.
93
Sesquiterpenoids
..-OH
(126) R
(127) R
=0
= CH2
(128) R = 0
(129) R = CH,
Full details of the neat synthesis of the ketone (126) and its methylenation to give
trichodiene (1 27) have been published.82 Unfortunately, sixteen attempts with
different reagents to carry out a similar methylenation of the diastereoisomeric
ketone (128) to give bazzanene (129) failed. A number of new and very interesting
trichothecane sesquiterpenoids have been isolated from Myrothecium verrucuriu.
These include trichodermadienediol A (130), trichoverrol A (1 3 I), and trichoverrin
A (132) together with their B counterparts which are epimeric at C-7.83 The
trichoverrins are clearly biosynthetic intermediates of the more toxic macrocyclic
>OH
(130) R
(131) R
=
=
H
OH
trichothecanes and indeed incubation of these two compounds gives rise to verrucarin A (133) and B (134) with smaller amounts of roridin A (135) and isororidin E
(1 36). In these experiments each recovered trichoverrin is uncontaminated with its
epimer, suggesting that each undergoes conversion into the macrocyclic compounds
via a common intermediate. In an elegant piece of carbohydrate chemistry Tulshian
and Fraser-Reida4 have synthesized the C-4 octadienic methyl esters derived by
methanolysis of the six metabolites isolated by Jarvis et al.83 As shown in Scheme 13
S. C. Welch, A. S. C. Prakasa Rao, C. G. Gibbs, and R. Y. Wong, J . Org. Chem., 1980, 45,
84
4077.
B. B. Jarvis, G. Pananasasivam, C. E. Lolmlund, T. DeSilva, G. P. Stahly, and E. P. Mazzola,
J. Am. Chem. SOC.,1981,103,472.
D. B. Tulshian and B. Fraser-Reid, J . Am. Chem. SOC.,1981, 103, 474.
94
HO---
Me
CH
OH
Me
CH
OH
__j
(137)
liii
OH
A c o y O j
AcO
(139)
__3
__3
C0,Me
(140)
C0,Me
O -C
(138)
Reagents: i , HgS0,-H,O+; ii, MeSiCH(Li)CO,Me; iii, NaOMe
Scheme 13
the syntheses start from the carbohydrate precursors (137) and (139). Whereas the
glucal (137) gives the D-erythro-ester (138) identical in all respects with the compound derived from the B series of metabolites, the galactal (139) produces the
D-threo-ester (140) which is enantiomeric with respect to the compound obtained
from the A series of metabolites. Coupling of the THP ether of verrucarol(l41) with
the acid (142) followed by deprotection and lactonization by the Corey-Mukaiyama
procedure has produced the verrucarin A derivative (143).85
E.-A. Notegen, M . Tori, and C. Tamm, Helv. Chim. Acfu 1981, 64, 316.
Sesquiterpenoids
95
~ T H P
oq
J.
vii
OMe
o%
OMe
hii-x
yy& qJ-&
XI, XI1
OMe
OMe
(14)
Reagents: i, NaBH,; ii, SOC1,-py; iii, Bu', AlH; iv, VO(acac),-Bu'OOH; v, MeI-NaH;
+ vi, Me,N--O; vii, H,O+; viii, MeLi; ix, Cr0,-py; x, POCl,-py; xi, Ph,P=CH,; xii, MCPBA
Scheme 14
96
C0,Me
(145)
Jii,
iii
IV-VI
f--
Me0,C i
(146)
(147)
Reagents: i, A ; ii, (CH,OH),-PTSA; iii, Me,CuLi; iv, LDA;
HC=CH; piii, Bu',AlH; ix, Ac,O-py; x, H,O+
Scheme 15
HO
W
v, vi
V,
PhSeC1; vi, H,O,; vii hv-
+
I
Me0,C
Me0,C
bii,viii, i
(148)
(149)
Reagents: i, A ; ii, Me,CuLi; iii, Bu',AlH; iv, H,O+; v, MeOH-H+; vi, MeMgI, vii, H + ;
viii, Ac,O-py
Scheme 16
Sesquiterpenoids
97
---+
OH
Me0,C
(145)
-@ -qo
i v , vi
Qo
Ho
vii-ix
x, x i
OMe
Me0,C
HO
Me0,C
(150)
Reagents: i, A; ii, Me,CuLi; iii, LDA; iv, MoO,*py.HMPA; v, NCS-Me,S; vi, Et,N; vii,
NaH-Mel; viii, Bu,AlH; ix, Et,SiH-BF,-Et,O; x, LiAlH,; xi, H +
Scheme 17
O
+
J
+
ii, iii
2
HO
ButMe,SiO
jiv, v
f--
CHO
HO
ButMe,SiO
ButMe,SiO
(151)
Reagents: i, B(OAc),; ii, BuMe,SiCI-imidazole; iii, K,C03-MeOH; iv, NCCH,COCl-py ;
v, DBN; vi, Bu,AIH; vii, Et,SiH-BF,*Et,O; viii, NaCIO,; ix, Et,N-ClC0,Et-NaN,; x,A-OH-;
xi, Bu,NF
Scheme 18
Ho
:
R
(152) R
(154) R
=
=
Me
(153)
0
(155)
Pearson and Ongas have extended their route to trichothecane sesquiterpenoids

via organoiron complexes by the synthesis of (144) (Scheme 14). The Diels-Alder
approach to the construction of the cis-fused AB ring junction of the trichothecanes has been much in evidence. The use of methyl coumalate (145) as a
66
A. J. Pearson and C. W. Ong, J . Am. Chem. Soc., 1981.103,6686; Tetrahedron Lett., 1980,21,
4641.
Terp'enoids and Steroids
98
dienophile features in three independent ~ y n t h e s e s . * ~In- ~the

~ first of theses7
(Scheme 15) the subsequent addition of the C ring involves a novel cyclobutenylcarbinol-cyclopentenyl rearrangement, ( 146)+( 147). A second synthesisss using
(145) (Scheme 16) achieves the conversion into (148) which has previously been
transformed into (149). Finally, a third routesQinvolving (145) (Scheme 17) has
been used to synthesize (1 50) which unfortunately has the endocyclic double bond
in the wrong position. The desired isomer (1 5 1) can be synthesized by a different
*Q
-
OPP
Diels-Alder-based strategy (Scheme 1Q g O An analogous route has also been

explored by Miller et aLQ1who obtained the acetoxy-aldehyde (152) from the
Diels-Alder reaction of 3-methylbuta- 1,3-dienyl acetate with 2-methylprop-2-enal.
Cyclization of (1 52) with sodium hydride gave the coumarin derivative (1 53).
Unfortunately, cyclization of the corresponding methyl ketone (154) yielded the
chromanone derivative (155) and not the methyl analogue of (153).
Cane et al.92have re-examined the biosynthesis of trichodiene (127) by incubation
of tran~,trans[l-~H,,l2,1
3-14C]farnesylpyrophosphate (1 56) [3H/14Catom ratio 2 :21
with a cell-free extract of Trichotlzecium roseum. A crystalline derivative of the
trans-diol derived from the endocyclic double bond of labelled trichodiene had a
\OPP
Scheme 19
J. D. White, T. Matsui, and J. A. Thomas, J . Org. Chem., 1981, 46, 3376.
Y . Nakahara and T. Tatsuno, Chem. Pharm. Bull., 1980, 28, 1981.
G. A. Kraus and K. Frazier, J . Org. Chem., 1980, 45,4820.
G . A. Kraus and B. Roth, J . Org. Chem., 1980, 45,4825.
91 R. E. Banks, J. A. Miller, M. J. Nunn, P. Stanley, T. J. R . Weakley, and Z. Ullah, J . Chem.
82 D. E. Cane, S . Swanson, and P. P. N. Murthy, J . Am. Chem. SOC.,1981, 103, 2136.
n7
nn
Sesquiterpenoids
99
(159) R
(160) R
=
=
OH
H
3H/14C
atom ratio of 1.8 :2 demonstrating that practically no loss of hydrogen from
C-1 of the precursor had occurred. This result is at variance with an earlier result by
Hanson and co-workers who claimed that loss of a C-1 hydrogen did occur in this
biosynthesis. Furthermore degradation of the labelled trichodiene clearly established
the position of the two tritium atoms as shown in (157). Cane's present evidence,
together with other findings in monoterpene and sesquiterpene biosynthesis,
strongly indicates that the biosynthesis of trichodiene (127) can be viewed as shown
in Scheme 19 with the involvement of nerolidyl pyrophosphate (158).58
Full details of two of the elegant syntheses of gymnomitrol (159)93794 and
gymnomitrene (160)94have been published.
6 Chamigrane, Widdrane
Full details of an earlier synthesis of chamigrene (161) have been published.95
Further work on the components of the red alga Laurencia nipponica Yamada has
resulted in the isolation and structural elucidation (by X-ray analysis) of the
diol (162)96and spironippol (164).97The biogenesis of the latter compound can
be viewed in terms of an intramolecular cyclization of the diol(l63) derivable from
the naturally occurring epoxide of 1O-bromo-a-chamigrene.
(163)
O4
O5
(164)
L. A. Paquette and Y.-K. Han, J. Am. Chem SOC.,1981, 103, 1831.

S. C. Welch, S. Chayabunjonglerd, and A. S. C. Prakasa Rao, J. Org. Chem., 1980, 45,4086.
J. D. White, J. F. Ruppert, M. A. Avery, S. Torii, and J. Nokami, J. Am. Chem. SOC.,1981,103,
1813.
O6
*'
K. Kurata, A. Furusaki, C. Katayama, H. Kikuchi, and T. Suzuki, Chem. Lett., 1981, 773.
A. Fukuzawa, C. M. Shea, T. Masamune, A. Furusaki, C. Katayama, and T. Matsumoto,
TetrahedronLett., 1981, 22, 4087.
100
An ingenious synthesis of widdrol (167) has been developedg8in which a key

step is the Claisen rearrangement of the vinyl lactone enolate (165) to give the
acid (166) (Scheme 20). This process proceeds via a boat-like transition state thus
controlling the relative stereochemistries of the two quaternary methyl groups at
C-4 and C-7.
b-vii
xiii, xi;
. O
\i
A
xv xvi
Lo
OSiMe,But
(165)
(166)
Lrvii, xviii, ii
(1 67)
Reagents : MeC(OEt),-EtC0,H; ii, LiAlH,; iii, MsC1-py; iv, NaI; v, NaH-CH,(CO,Me),;
vi, MeOH-OH-; vii, A-py; viii, NBS; ix, MCPBA-TBP; x, Zn-MeOH; xi, OH-; xii, TFA;
+xiii, LDA-MeI; xiv, LDA-Bu'Me,SiCl; xv, 110 "C; xvi, Bu,NF; xvii, SOCI,; xviii, MCPBA
Scheme 20
7 Acorane, Carotane, Cedrane, Zizaane

Previously it had been shown that low temperature irradiation of the enone (168)
gave the tricyclic ketone (169) as the major product. It has now been reportedgg
that further photolysis of (169) at 0-5 "C promotes a Norrish type I1 process to
give the ketone (170) which can be converted into oc-acoradiene (171). Epimerization
of the isopropenyl group in (170) can be achieved by silver nitrate, thus paving
the way for a synthesis of acorenone B (172). Pertinent to these results is the finding
98
S. Danishefsky and K. Tsuzuki, J . Am. Chem. SOC.,1980,102,6891.

D. D. K. Manh, J. Ecoto, M. Fetizon, H. Colin, and J.-C. Diez-Masa, J . Chem. SOC.,Chem.
Commun., 1981, 953.
Sesquiterpenoids
101
by Oppolzer et al.loOthat photocycloaddition of (173) gives (174) which then undergoes reductive ring-opening with lithium in liquid ammonia to produce the spiroketone (175). Full details of an alternative strategy for the synthesis of acorenone B
(172) have been presented.95Another interesting approach to this class of sesquiterpenoid is that adopted by Ficini et al.lol in which the spiroannelation step is
achieved by reaction of the enol lactone (176) with the ynamine (177) to give (178).
Me
P
p
loo
lol
W. Oppolzer, L. Gorrichon, and T. G. C.Bird, Helv. Chim. Acra, 1981, 64, 186.
J. Ficini, G. Revial, and J. P. GenCt, Tetrahedron Lett., 1981, 22, 629, 633.
102
The stereoselectivity of this reaction can be rationalized in terms of cyclization of

the intermediate (179). A double Wittig reaction transforms (178) into (180).
Hydrolysis of this enamine gives the enone (1 8 1) which can be isomerized by PTSA
to produce (182). The synthesis of acoradiene I11 (183) was finally completed by
reduction to the allylic alcohol followed by a further reduction of the derived diethyl
phosphate. A full paper on the interesting rearrangement of carotol (184) with
tluonyl chloride in pyridine to give the acoradienes (183) and (185) has been
published.lo2Similar treatment of dihydrocarotol does not give rearranged products,
thus indicating that the double bond in carotol is essential for migration to occur.
It has been claimed that (186) is a new carotane derivative isolated from the
Compositae species Inula ~rithrn0ides.l~~
There is little doubt, however, that this
compound is in fact vaginatin, first reported in 1968.14
The first cedrene synthesis by Stork and Clarkelo5 over twenty years ago was
achieved via the tricyclic dione (187). This compound has now been synthesized by
(1 87)
Reagents: i, h v ; ii, Me,CuLi, iii, NaCI-H,O-DMSO;
vi, H2-Pt; vii, Bu'OK
Scheme 21
iv, H C r CLi; v, HC0,H-H2S0,;
L. H. Zalkow, M. G. Clover, Jr., M. M. Gordon, and L. T. Gelbaum, J . Nut. Products, 1980,

43, 382.
103 2. F. Mahmoud, N. A. Abdel Salam, T. M. Sarg, and F. Bohlmann, Phytochemisrry, 1981, 20,
735.
lo4 K. Rajendran, S. K. Paknikar, G. K. Trivedi, and S. C. Bhattacharyya, Indian J. Chem.,
Sect. B, 1978,16,4; C. K. Mesta, S. K. Paknikar, and S. C. Bhattacharyya, Chem. Commun.,
1968, 584.
lo5 G. Stork and F. H. Clarke, Jr., J . Am. Chem. Soc., 1955, 77, 1072; 1961, 83, 31 14.
lo2
Sesquiterpenoids
103
an entirely new route (Scheme 21).lo6A very ingenious short synthesis of cedrene
(191) has been announced, which differs totally from previous syntheses in its
conception (Scheme 22).Io7The success of this synthesis hinged upon a detailed
(191)
( 190)
t 189)
Reagents: i, Li-NH,-NH,CI; ii, h v ; iii, Br,; iv, Bun,SnH; v, NH,NH,-OH-
Scheme 22
mechanistic consideration of the intramolecular photochemical cycloaddition of the

arene-alkene (188) in terms of regioselectivity and stereoselectivity. These considerations led Wender and Howbert to predict accurately the outcome of this reaction
which produces two, (189) and (190), of the thirty-six possible cycloadducts.
On thermolysis, perezone (192) undergoes a [4 +2] cycloaddition to produce
equal amounts of the two pipitzols (193) and (194) i.e. there is no stereochemical
induction by the chiral centre in (192). If, however, the reaction is carried at
0 "C in the presence of boron trifluoride etherate the cyclization becomes highly
stereoselective producing largely a-pipitzol (193) and it has been shown that a
stepwise mechanism ( 1 9 9 4196)+( 193) is operative in thls case.loS
A previously uncharacterized sesquiterpene, a-duprezianene (197), has been
isolated from Cupressus dupreziana and has been assigned this structure on the
basis of spectral data together with its co-occurrence with ( +)-a-funebrene
(198).Io9Scheme 23 illustrates a possible biogenetic relationship between these two
hydrocarbons. (-)-Prezizanol(201) and ( -)-prezizaene (202) have been synthesized
starting from the cyclopentanone derivative (199) which can be derived in three
steps from ( +)-pulegone (Scheme 24).llo The drawback in this synthesis is that the
diazo-ketone derived from (200) also gives an almost equal amount of an isomeric
tricyclic ketone by insertion into the alternative methylene group. Recently the
K. E. Stevens and P. Yates, J. Chem. SOC.,Chem. Commun., 1980, 990.
P. A. Wender and J. J. Howbert, J . Am. Chem. SOC.,1981, 103,688.
l o 8 I. H. Sanchez, R. Yaiiez, R. Enriquez, and P. Joseph-Nathan, J . Org. Chem., 1981, 46, 2818.
l o B J. K. Kirtany and S. K. Paknikar, Indian J . Chem., Sect. B, 1981, 20, 506.
1 l 0 P. R. Vettel and R. M. Coates, J. Org. Chem., 1980, 45, 5430.
log
lo7
104
a
H
(??-
(-fJ
H
(198)
(197)
Scheme 23
prezizaene alcohol, jinkohol, has been ascribed the structure (2O3).l1l This is the
same structure as that put forward for ( +)-allokhusiol,'12 although the Japanese
workers seemed to be unaware of this. There is a very close similarity in the spectral
data for the two compounds except for the optical rotations ([.ID of jinkohol
claim that jinkohol (203)
-6..l', [aID of allokhusiol +45'). Nakanishi et
is not identical to the enantiomer of (201) ([aID -48.3') isolated by Carrol et al.l13
some years ago. Ganguly et
also made the same claim about the non-identical
*I2
113
T. Nakanishi, E. Yamagata, K. Yoneda, and 1. Miura, Phytochemistry, 1981, 20, 1597.

R. N. Ganguly, G . K . Trivedi, and S. C. Bhattacharyya, Indian J. Chem., Sect. B, 1978, 16,20.
P. J. Carrol, E. L. Ghisalberti, and D. E. Ralph, Phytochernistry, 1976, 15, 777.
Sesquiterpenoids
105
Jvi, vii, v
xi
t
VIII-x
(20 1)
(202)
Reagents: i, MVK-Et,N; ii, Q - H O A c ; iii, H,-Pd/C; iv, (CH,OH),-H+; v, LiAlH,;

H
vi, MsCl-Et,N; vii, NaCN-Et,NCl; viii, PhCOCl; ix, H,O+; x, N,O,; xi, KOBu'; xii, KH-MeI;
xiii, MeLi
Scheme 24
mirror image relationship of ( +)-allokhusiol and Carrol's alcohol, but considered

(+)-allokhusiol to be the enantiomer of Tomita's alcohol ( [ Q ] ~4 6 . 2 " ) derived
from solvolysis of the brosylate of allocedrol (2O4).ll4 Carrol et al., however,
claimed that their alcohol was identical to Tomita's alcohol and thus there is some
confusion in the literature concerning the structures of the four ( ?) tricyclic alcohols.
Further work needs to be done with these compounds to clarify the situation.
One of the original syntheses of zizaene (210) utilized the tricyclic ketone (209)
as a key intermediate. A third synthesis of this compound has now been accomplished (Scheme 25)115 by an internal photochemical cycloaddition of (205) to
give (206) as the major product. A subsequent Grob fragmentation of the P-alkoxide
derived from (207) gave (208) from which the ketone (209) (together with its
methyl epimer) could be derived by hydrogenation.
114
115
B. Tomita and Y . Hirose, Phytochemistry, 1973, 12, 1409.

A. J. Barker and G . Pattenden, Tetrahedron Lett., 1981, 22, 2599.
106
AcO
c&
ii iii
+
1
Reagents: i, h v ; ii, NaBH,; iii, MsC1-py; iv, NaOH; v, H,-Pd/C
Scheme 25
8 Cadinane, Cubebane, Oplopanane, Picrotoxane, Sativane,

Copacamphane
A detailed n.m.r. investigation has provided further confirmation of the structures

of torreyol (21 l), a-cadinol (212), T-muurolol (213), and T-cadinol (214).l16
New additions to this group of sesquiterpenoid include the ageraphorones (215)(219) (Ageratina adenophora)l17 and the muurolane-type acid (220) (Trichogonia
grazielae).lls The phenolic cadinanes (221)-(224) have been isolated from Bombax
malabaricum.llg The two hydroxy-cadalenes (225) and (226) have been detected in
green and field-dried cotton bracts.120Autoxidation of these compounds leads to
lacinilene C (227) and its methyl ether. The latter has been implicated in the chronic
respiratory disease, byssinosis.
A.-K. Borg-Karlson, T. Norin, and A. Talvitie, Tetrahedron, 1981, 37, 425.

F. Bohlmann and R. K. Gupta, Phytochemistry, 1981, 20, 1432.
118 F. Bohlmann, C. Zdero, J. Pickard, H. Robinson, and R. M. King, Phytochemistry, 1981, 20,
1323.
119 A. V. B. Sankaram; N. S. Reddy, and J. N. Shoolery, Phytochemistry, 1981, 20, 1877.
no R. D. Stipanovic, G. A. Greenblatt, R. C. Beier, and A. A. Bell, Phytochemistry, 1981, 20,729.
11'
Sesquiterpenoids
107
H :
(215) R
(216) R
=H
= OH
(217) R
(218) R
0
= P-OH, H
=
OR1 CHO
CHO
R20q
Hod Ho
HOaC
(221) R1= Me, R2 = H

(222) R1= R2 = Me
(224)
(225) R
(226) R
=
=
(227)
H
Me
The sesquiterpenoids (228)-(234), previously isolated from Heterotheca

species, have all been synthesized.121 Further work on the photoadduct (235)
derived from methyl cyclobutenecarboxylate and ( -)-piperitone has demonstrated
the important synthetic utility of this compound.122Flash vacuum pyrolysis of (235)
at 500 "Cgives (236)-(240). Additional thermolysis experiments showed that (237)
and (238) are the precursors of (236) and that this compound undergoes a further
(228) R
(229) R
=
=
H
Me
(231) R
(232) R
lal
19z
CH20H
CO,H
Hod
\
=
=
F. Bohlmann and W. Mailahn, Chem. Ber., 1981, 114, 1091.

J. R. CIiIliams and 1. F. Callahan, J. Org. Chem., 1980, 45, 4479.
108
intramolecular ene reaction to form (240) which has been chemically converted into
( +)-isocalamendiol(241). The epimeric mixture of bicyclic enones (242) which have
previously been converted into epizonarene (243) has been synthesized (Scheme
26).123A similar type of intramolecular Diels-Alder methodology has been used to
--+
Li+
l i i , iii
iv
t--
(243)
(242)
Reagents: i, 180 "C;ii, RaNi; iii, Cr0,-H+; iv, PTSA
Scheme 26
convert the acyclic enone (244) into the octalone (245), which, on treatment with
N-methylanilinium trifluoroacetate and paraformaldehyde, gave (246).lZ4This is
123
12'
S. R. Wilson and R. N. Misra, J . Org. Chem., 1980, 45, 5079.

J.-L. Gras, J . Org. Chem., 1981, 46, 3738.
109
Sesquiterpenoids
0
(244)
(245)
(246)
R
R
= H2
= CH,
(247)
the structure originally assigned to chiloscyphone but since the synthetic and
natural materials are not identical, the structure of natural chiloscyphone must be
in error. Another variant of the intramolecular Diels-Alder reaction, this time using
Reagents: i, EtMgBr-DMF; ii, Me,SiCN-ZnI,; iii, Bu"Li; iv, MeCH=CHCO,Bu'; v, F-;

vi, H,-Pd/C-HClO,; vii, PPE; viii, MeC(OAc)=CH,-H+; ix o-chloranil; x, NaBH,; xi, A ;
xii, Me,SO,-OHScheme 27
110
a benzyne intermediate, has been devised for the synthesis of mansonone E (249).126
Thus, generation of the substituted benzyne (247) from the corresponding anthranilic
acid spontaneously cyclizes to produce (248), which could be converted into
mansonone E (249) by standard means. Gossypol(250) is a well known constituent
of cottonseed pigment, and recently considerable interest has been generated in this
compound because of the reported male contraceptive properties of its acetate and
formate. A reasonably efficient synthesis of the nor-gossypol derivative (252) from
the bromobenzene (25 1) has been recorded (Scheme 27).lZ6Attempts to synthesise
the interesting cadinane sesquiterpenoid, arteannuin B (253), have been made
but the principal route used (Scheme 28) has only produced the stereoisomers
(254)-(256) none of which is identical to the natural product.lZ7
A re-investigation of the brown alga Dictyopteris diuaricata has resulted in
the identification of the new alcohol, epicubebol (257) together with the known
ii-iii
+
0
0
~\
0
(254)
0 :
\
0
(255)
q
H i
H i
(256)
Reagents: i, CH,=C(Li)C(OEt),; ii, H,O+; iii, Me$-NBS; iv, Zn/Cu; v, MCPBA
Scheme 28
lZ5
IZ6
12'
W. M. Best and D. Wege, Tetrahedron Lett., 1981, 22,4877.

M. C. Venuti, J . Org. Chem., 1981, 46, 3124.
0. Goldberg, I. Deja, M . Rey, and A. S. Dreiding, Helv. Chim. Acta, 1980, 63, 2455.
111
Sesquiterpenoids
(258) A3*4
(259) A49I5
(257)
(26 1)
(262)
(263)
compounds, ( -)-a-cubebene (258), ( -)-p-cubebene (259), epicubenol (260),
cubenol (261), and ( +)-8-cadinene (262).12*
Several new oplopanane sesquiterpenoids, exemplified by implexin (263),
have been isolated from various Senecio s p e ~ i e s . ~ ~ Another
~ J ~ O synthesis of
oplopanone (264) has been recorded (Scheme 29).131
In a continuation of his work on dendrobine synthesis, R o u s ~ Ihas
~ ~found
that the intramolecular Diels-Alder reaction of the diene-ester (265) gives predominantly the bicyclic compound (266). This was an unexpected result because
viii-x
vi, vii
f--
0
(264)
Reagents: i, Li-NH,-Bu'OH; ii, BunLi; iii, Me,C=CH(CH,),Br ; iv, HCl; v, Ac,O-HOAc+-
HC10,; vi, KOH-MeOH; vii, Me,SCH,; viii, LiAlH,; ix, 0,;

x, KOBu'
Scheme 29
M. Suzuki, N. Kowata, and E. Kurosawa, Bull. Chem. SOC.Jpn., 1981, 54, 2366.
l Z 9F. Bohlmann, M. Ahmed, J. Jakupovic, and C. Jeffery,Phytochemistry, 1981, 20, 251.
130 F. Bohlmann, C. Zdero, and R. K. Gupta, Phytochemistry, 1981, 20, 2924.
lS1 F.-H. Koster and H. Wolf, TetrahedronLett., 1981, 22, 3937.
132 W. R. Roush and H. R. Gillis, J. Org. Chem., 1980, 45,4283.
12*
112
the stereochemistry of the product indicates that a kinetically controlled e m

addition has been favoured in this case. Hydrolysis of (266) gives the keto-ester
(267) which has previously been used for the synthesis of dendrobine (268) (Vol. 11,
p. 32).
vii
t-
MesSiO
C02Me
h i i , ix, iv, x
i , xi, xii
c
xiii
OSiMe2But
OSiMe,But
'
OSiMe,But
biv-xvi,
iv
(269)
Reagents: i , LDA; i i , [ O F 1 ; iii, MeLi; iv, H,O+; v, (MeO),P(O)CHCO,Me; vi ZnC1,0
Me,SiCl-Et,N; vii, I10 "C; viii, (CH,OH),-H+; ix, LiAlH,; x, Bu'Me,SiCI; xi, Me3SiC1;
xii, Zn/Cu-CH,I,; xiii, Feel,; xiv, H,-Pd/C; xv, Me,C=PPh,; xvi, H,-PtO, ; xvii, Bu3Pa0,NArSeCN-py; xviii, H,02
Scheme 30
Sesquiterpenoids
113
viii, ii, ix, v
S0,Ph
%l
x-xiii
(270)
Reagents: i, LiBr; ii, NaCN; iii, PhSCl; iv, Bu',AlH; v, H,O+; vi, LiBHEt,; vii, MCPBA;
viii, MsCI-Et,N; ix, MeOH-H+; x, KN(SiMe,)2; xi, LiAlH,; xii, Li-EtNH,; xiii, CrO;py,;
xiv, Ph,P=CHOMe; xv, K,CO,-MeOH; xvi, MeLi ; xvii, Ph,P=CH,; xviii, H2-(Ph,P),RhC1
Scheme 31
A very neat synthesis of sativene (269) has been reported by S n ~ w d e n(Scheme

l~~
30) which yet again illustrates the considerable synthetic advantages of the intramolecular [4 +21 cycloaddition. Heissler and RiehP3*have extended their methodology of homoconjugate addition of phenylsulphenyl chloride to methylenenorbornenes for the construction of tricyclene derivatives (Vol. 10, p. 18) to
the synthesis of cyclosativene (270) (Scheme 31). They have also synthesised the
(274).
laa
R. L. Snowden, Tetrahedron Lett., 1981, 22, 97, 101.

D. Heissler and J.-J. Riehl, Tetrahedron Lett., 1980, 21, 4707
(275)
114
C,, hydrocarbon (271)135by a similar route but this compound is not identical to a
tricyclic hydrocarbon isolated from East Indian sandalwood oil and reported to
have this structure. (+)-Copacamphor (272) and ( +)-copaborneol(273) have been
isolated from Espeltiupsis g u a c h a r a ~ aThe
. ~ ~interesting
~
sinularene derivative (274)
and the acetoxycyclosinularane (275) have been isolated from the marine source,
Clavularia i n 3 ~ a t a .These
l ~ ~ compounds, together with an aromadendrane derivative
(see p. 18 1) are the first sesquiterpenoids from Octocorallia of the order Stolonifera.
9 Himachalane, Longifolane, Longipinane
a- (278) and p-Himachalene (279) have been synthesized (Scheme 32).138 This
route is not particularly attractive in view of the low yield (12%) at the isomerization step (276)+(277). The himachalenes can be converted into ar-himachalene
(280) with 5 % palladium on carbon and various himachalenes with trans ring
fusion can be prepared by treatment of the himachalenes with hydrochloric
acid followed by base-induced dehydroch10rination.l~~
The lzlmachalanolide (281)
Me02C
Me0,C
__+
a
Jiv, v
2Et
vi
(278)
(279)
Reagents: j, SnCI,; ii, Et,SiH-(Ph,P),RhCI; iii, aq. K,CO,; iv, LiI-collidine; v, N,CHCO,EtBF,.Et,O; vi, PTSA; vii, MeLi; viii, POCI,-py
Scheme 32
135
136
13'
138
139
D. Heissler and J.-J. Riehl, Tetrahedron Lett., 1980, 21, 471 1.

F. Bohlmann, H. Suding, J. Cuatrecasas, H. Robinson, and R. M. King, Phyruchemistry, 1980,
19, 2399.
J. C. Braekman, D. Daloze, A. Dupont, B. Tursch, J. P. Declercq, G. Germain, and M. Van
Meerssche, Tetrahedron, 1981, 37, 179.
H.-J. Liu and E. N. C. Browne, Can. J. Chem., 1981, 59, 601.
J. Daunis, R. Jacquier, H. Lopez, and P. Viallefont, J . Chem. Res. ( S ) , 1981,45; A. B. Harref,
A. Bernardini, S. Fkih-Tetouani, R. Jacquier, and P. Viallefont, ibid., 1981,372.
Sesquiterpenoids
115
has been isolated from Acritopappus Z ~ n g i f o l i u s and

~ ~ ~ the seco-himachalane
derivative, himasecolone (282), from Cedrus deodara.141
Over the past 25 years longifolene (283) has been the focus of many aspects of
chemical research-synthesis, molecular rearrangements, transannular reactions,
and biosynthesis. All these and other details of longifolene chemistry have been
thoroughly reviewed by Sukh Dev142who himself has made many major contributions in this area of natural product chemistry. (+)-Longifolene can be
converted into crystalline di10ngifolylborane.l~~
This chiral dialkylborane can
(280)
(28 1)
(282)
be used for the asymmetric hydroboration of cis-disubstituted, trisubstituted

acyclic, and cyclic prochiral olefins to provide alcohols with optical purities
in the range of 60-78% enantiomeric excess. In the cases studied to date the
predominant alcohol is of the R-configuration.
An X-ray analysis of rastevione, the main constituent of the roots of Stevia
serrata and S . rhombifolia, has revealed it to have structure (284).144This definitive
assignment calls into question the relative stereochemistry assigned to more than
fifteen other longipinene and longipinane derivatives isolated from various plant
sources (see Vol. 7, p. 75, Vol. 9, p. 110, Vol. 10, p. 34). The tiglate (285) has been
isolated from Eupatoriadelphusp ~ r p u r e u s . ~ ~ ~
(283)
10 Caryophyllane, Humulane, and Related Sesquiterpenoids

Force field calculations have been applied to caryophyllene and four basic conformers (286)-(289) have been identified of which (286) and (288) contribute 75 % and
2 1 % re~pective1y.l~~
The energy barrier to conformational interconversion at 35 "C
F. Bohlmann, R. K. Gupta, H. Robinson, and R. M. King, Phytochemistry, 1981, 20, 275.
P. K. Agarwal and R. P. Rastogi, Phytochemistry, 1981, 20, 1319.
14* S. Dev, Acc. Chem. Res., 1981, 14, 82; S. Dev in 'Progress in Chemistry of Organic Natural
Products', ed. W. Herz, H. Grisebach, and G. W. Kirby, Springer-Verlag, Wein, 1981, Vol. 40
p. 49.
143 P. K. Jadhav and H. C. Brown, J . Org. Chem., 1981, 46,2988.
lQ4L. U. Roman, R. E. del Rio, J. D. Hernindez, P. Joseph-Nathan, V. Zabel, and W. H. Watson,
Tetrahedron, 1981, 37, 2769.
lQ6
F. Bohlmann, M. &hmed, R. M. King, and H. Robinson, Phytochemistry, 1981,20, 2027.
146 H. Shirahama, E. Osawa, B. R. Chhabra, T. Shimokawa,T. Yokono, T. Kanaiwa, T. Amiya,
and T. Matsumoto, Tetrahedron Lett., 1981, 22, 1527.
lQo
lQ1
116
U
(290)
Hd
jgco2H
jf--J-..
H"
H'
(297) R
(298) R
(300)151
=
=
(299)
H150
OAcl5'
(301)152
has been calculated to be 16.25 kcal mol-1 based on a line shape analysis of certain
peaks in the 13C n.m.r. spectrum. This leads to the conclusion that the two conformers (286) and (287) contribute 76% to the population equilibrium while
conformers (288) and (289) contribute 24 %. The barriers to the interconversion of
(286) and (287) and to (288) and (289) will be very small and it is interesting to note
that earlier
clearly indicated that conformer (287) leads to clovene (290) and
conformer (288) to P-caryophyllene alcohol (29 1) on acid-catalysed rearrangement
of caryophyllene. Various oxygenated caryophyllene derivatives (292)--(301)148-152
have been identified as constituents in a number of plant species.
The number of sesquiterpenoids which can be formally derived from a caryophyllene-type precursor has risen quite dramatically in the last few years and
includes the following structural types :147
148
149
l50
151
152
A. Nickon, F. Y. Edarnura, T. Iwadare, K . Matsuo, F. J. McGuire, and J. S. Roberts, J . Am.

Chem. Soc., 1968,90,4196.
F.Bohlmann, U.Fritz, R. M. Kinf, and H. Robinson, Phytochemistry, 1980, 19, 2655.
F.Bohlmann and R. Bohlmann, Phytochemistry, 1980, 19, 2469.
F. Bohlmann, C.Zdero, H. Robinson, and R. M. King, Phytochemistry, 1980, 19, 2381.
F. Bohlrnann, A. K. Dhar, J. Jakupovic, R. M. King, and H. Robinson, Phytochemistry, 1981,
20, 1425.
F. Bohlmann, L. Miiller, R. M. King, and H. Robinson, Phytochemistry, 1981, 20, 1149.
Sesquiterpenoids
117
Neoclovane
Panasinsane
Quadrane
Koraiane
Silphiperfolane
Presilphiperfolane
Isocomane
Modhephane
Senoxydane
Silphinane
Botrydiane
Senecrassiane
A new addition to this ever-growing group is senecrassidiol (302) which has

been isolated from Senecio crassissirnus and it has been suggested that this compound with its unusual cis ring fusion may be formed from the co-metabolite
(303) by transannular hydration.59Previously Bohlmann and Z d e r ~had
l ~ identified
~
the rare epi-caryophyllene (304) in Euryops brevipapposus and converted it into
(303) by epoxidation. Another new skeleton is seen in the structure of 8-hydroxypresilphiperfolene (305), isolated from Eriophyllum staechadiJ~Ziurn.~~~
This
interesting tricyclic alcohol is the missing link in the proposed biogenesis of
the silphinane and silphiperfolane sesquiterpenoids from caryophyllene (Vol. 11,
p. 50) The silphiperfolene derivative (306) has also been identified recently in
Espeletiopsis g u ~ c h a r a c a . ~ ~ ~
153
154
F. Bohlmann and C. Zdero, Phytochernistry, 1978, 17, 1135.

F. Bohlmann, C. Zdero, J. Jakupovic, H. Robinson, and R. M. King, Phytochernistry, 1981,20,
2239.
118
As mentioned in previous reports the structures of many of these metabolites

which incorporate three angularly fused cyclopentane rings (triquinanes) have
stimulated a flurry of synthetic interest with the result that four independent
and imaginative syntheses of both isocomene (307) and modhephene (308) have
been recorded so far. In addition to other sources these compounds co-occur
in the roots of Otanthus r n a r i t i m ~ sIn
. ~ the
~ ~ case of isocomene (307), full reports
of the P a q ~ e t t e and
l ~ ~P i ~ r u n g syntheses
l~~
have appeared. The full Pirrung paper
draws attention to the mechanistically interesting aspect of the final step in his
isocomene synthesis. On the one hand, treatment of (309) with PTSA gives isocomene (307) exclusively, whereas similar treatment of the ketone (310) gives (31 1)
and (312) in the ratio of 5 : 1. Further reaction of (311) with methyl-lithium gives
a tertiary alcohol mixture, which on treatment with formic acid once again produces isocomene (307). Thus the rearrangement of (309) to give isocomene (307)
could involve at least two pathways (or a mixture of both) (Scheme 33). The
Scheme 33
conversion of (310) into (309) with 13CH2=PPh3 could provide some insight
into this mechanism since the fate of the labelled carbon is different for the two
pathways. The latest synthesis of isocomene (Scheme 34)15* involves a classical
construction of the triquinane nucleus terminating with the tricyclic ketone (3 13),
which Paquette had already converted into isocomene in three steps.
Turning now to the intriguing propellane sesquiterpene modhephene (308),
Karpf and Dreidingls9 have provided full details of their original synthesis. Hot
155
J. de Pascual, A. San Feliciano, A. F. Barrero, M. Medarde, and F. TomC, Phytochemistry,

1981, 20, 166.
L. A. Paquette and Y.-K. Han, J . Am. Chem. SOC.,1981, 103, 1835.

M. C. Pirrung, J. Am. Chem. SOC.,1981, 103, 82.
W. G. Dauben and D. M. Walker, J . Org. Chem., 1981, 46, 1103.
M. Karpf and A. S. Dreiding, Helv. Chim. Acta, 1981, 64, 1123.
*I6
157
lS8
Sesquiterpenoids
119
C0,Me
- /$
C0,Me
v , v i M e 0 2 C @ T e .CO,Me
C0,Me
vii, vi
\co2Me
C0,Me
t
+
Me0,C
mco2
0
0
C0,Me
Ae
0
0
k i i , xiii, x
(313)
Reagents: i, LDA; ii, Br(CH,), C0,Et; iii, NBS-aq. MeCN; iv, MeOH-pH 6.8; v, H,O+-A;
vi, KF.2H20-MeI; vii, Me,C(CH,OH),-PTSA; viii, H 3 0 + ix, NH,NH2-KOH; x, PTSA;
xi, Me1 ; xii, (CH,SH),-BF,.EtO,; xviii, Ph,P=CH,; xiv, MeI-CaC0,-aq. MeCN
Scheme 34
on the heels behind this synthesis have followed another three syntheses. The
first of theselG0(Scheme 35) hinges upon the successful application of the acidcatalysed Cargill rearrangement of the strained [4,3,2]propellanes (315) and
(319) to give (3 17) uniquely. The initial photo-addition of 1,Zdichloroethene to
the enones (314) and (318) was surprisingly not stereospecific. In the case of (314)
the desired isomer (315) was the minor one [ratio (315):(316) = 1 :2], while for
(318) the required isomer was more abundant [ratio (319):(320) = 3:2]. The
next synthesis of modhephene (308) (Scheme 36)la1 owes its success largely to the
intramolecular ene reactions (321)+(322) and (323)+(324) originally developed by
Conia. Unlike Smith's synthesis, this route achieves the stereocontrolled synthesis of
160
A. B. Smith, 111 and P. J. Jerris, J . Am. Chem. SOC.,1981, 103, 194.

H. Schostarez and L. A. Paquette, J. Am. Chem. SOC.,1981, 103, 722.
120
Jviii, ix, v
. .
I-IV
(318)
(319)
(320)
(308)
Reagents: i, hv-ClCH=CHCl; ii, (CH,OH),-H+; iii, Na-NH,; iv, H,O+; v, PTSA; vi, MeLi;
vii, CrO,-H+; viii, Me,CuLi-BF,.EtO,; ix, CH,=PPh,
Scheme 35
~)
-._
).$p
t
vii,viii
--
@)
o
--.
-- . _ _
(324)
(323)
(325)
Reagents: i, Me,SiC = C(CH,),MgCl-CuI-BF,.Et,O ; ii, Bu,NF; iii, 360 "C; iv, Ph,P=CH,;
v, MCPBA; vi, BF,.Et20; vii, I,; viii, K,C03-NH,NH,; ix, H,C=CH(CH,), MgBr-CuIBF,*Et,O
Scheme 36
Sesquiterpenoids
Reagents: i, CH,=CH(CH,),MgBr;
121
ii, H,O+; iii,[o>(CH,),MgBr
-CuBr.Me,S; iv, OH-;
v, MsC1-py; vi, DBN; vii, 250 "C; viii, H,-Pd/C; ix, LDA; x, PhSeBr; xi, H202;
xii, MeMgICuBr.Me,S
Scheme 37
both modhephene (308) and epimodhephene (325). Finally Oppolzer's approachlg2

to modhephene (Scheme 37) results in a stereoselective synthesis in which the
crucial step is another intramolecular ene reaction (326)+(327) whose transition
state ensures the correct orientation of the newly created secondary methyl group,
The superb synthesis of quadrone (328) announced last year from Danishefsky's
group has now been reported in
A second synthesis of this complex fungal
metabolite has been reported (Scheme 38).163bThe basic strategy of this latest
synthesis parallels Danishefsky's approach in a number of points but overcomes
the regiochemical difficulties of introducing the lactone ring of the natural product.
A full account of the biosynthetic origin of dihydrobotrydial (331) from labelled
acetate and mevalonate has been
A number of the finer points in the
biosynthesis of this class of sesquiterpenoid have also been established.lg5Jg6
Thus by a careful and detailed study of the 2H and 13Cn.m.r. spectra of appropriate
metabolites after feeding the fungus Botrytis cinerea with [4JH2,4-13CJmevalonic
acid, it was established that a 1,3-hydrideshift takes place (329)+(330) (Scheme 39).
For example, the 2H n.m.r. spectrum of the ethyl acetal derivative of (331) showed
a singlet for H-2 and doublets for H-1 and H-5. This result clearly distinguishes
two consecutive 1,2-hydride shifts which would have produced an n.m.r. spectrum
with two singlets and one doublet (for H-5). This observation was verified from the
13C n.m.r. spectrum. Furthermore the origin of the oxygen atom of the tertiary
alcohol at C-9 has been traced to water since a study of the mass spectrum of the
lea
W. Oppolzer and F. Marazza, Helv. Chim. Acta, 1981, 64, 1575.
163
(a) S. Danishefsky, K. Vaughan, R. Gadwood, and K. Tsuzuki, J . Am. Chem. SOC.,1981,103,
4136; (b) W. K. Bornack, S . S. Bhagwat, J. Ponton, and P. Helquist, J . Am. Chem. SOC.,1981,
103, 4647.
164 A. P. W. Bradshaw, J. R. Hanson, and R. Nyfeler, J. Chem. SOC.,Perkin Trans. 1 , 1981, 1469.
le6 A. P. W. Bradshaw, J. R. Hanson, and R. Nyfeler, J . Chem. SOC.,Chem. Commun., 1981,649.
lee A. P. W. Bradshaw, J. R. Hanson, and I. H. Sadler, J . Chem. SOC.,Chem. Commun., 1981,1169.
122
pi-xi
Jxvii
f.3
C0,Me
v, xviii,
v, xix
xx
_j
HO
H02C
$OAc
OX0
Reagents: i, CH,=CHMgBr-CuBr.Me,S ; ii, Me,SiCl-Et,N iii, MeLi ; iv, BrCH,C(OEt)=
CHPO(OMe),; v, H,O+; vi, NaH; vii, PhSCHLiC0,Me; viii, CH,O; ix, aq- NH,Cl; x, NaBH,;
xi, Me,C(CH,OH),-H+; xii, Li-NH,; xiii, 9-BBN; xiv, H,O,-OH-; xv, TsC1-py; xvi, NaI;
xvii, LiN(SiMe,),; xviii, OH-; xix, Ac,O-py; xx, PCC; xxi, 200 C
Scheme 38
from C-4 of mevalonic acid

Scheme 39
Sesquiterpenoids
123
ethyl acetal of (331) obtained from B. cinerea grown on a H2 l8O medium clearly
shows l80incorporation at C-9. These results are in accord with Scheme 39 which
involves inversion of configuration at C-9 as a result of the 1,3-hydride shift.
(332)
(333) R
(334) R
(335) R
NO
(336)
= ONO,
=
NO2
An examination of the products derived from humulene (332) on treatment

with glacial acetic acid and sodium nitrite has revealed the formation of three
major compounds (333)-(335),167 the first of which is the blue crystalline nitrosite
prepared over eighty years ago by Chapman168and used as a means of distinguishing
a-caryophyllene (now known as humulene) from p-caryophyllene. Further treatment of the nitrosite under the same conditions produced a plethora of diamagnetic and paramagnetic (nitroxides) products for which a number of structures
have been proposed some of which are rather tentative. It is surprising that this
paper makes no mention of the formation of the isohumulene (336) from the
nitrosite", analogous to the formation of isocaryophyllene from caryophyllene
nitrosite.
Direct methods of converting humulene (332) into its 8,9-monoepoxide (337)t
and into zerumbone (338) have proved to be very inefficient. Shirahama et al.
have now brought about these conversions by indirect means. Thus, for the epoxide
(337),169 humulene is first transformed to the acetate (339) by treatment with
boron trifluoride etherate in glacial acetic acid followed by mono-epoxidation.
Reduction of this acetate with LiAlH, followed by elimination with mesyl chloride
in pyridine gives the epoxide (337). In the case of zerumbone (338),170 the readily
(337)
167
lE8
le0
1
'
0
(338)
(339)
(340)
D. K. MacAlpine, A. L. Porte, and G. A. Sim, J . Chem. SOC.,Perkin Trans. I , 1981, 999.

A. C. Chapman, J. Chem. SOC.,1895,67,54, 780.
B. R. Chhabra, H. Shirahama, and T. Matsumoto, Chem. fnd., 1981, 539.
H. Shirahama, B. R. Chhabra, and T. Matsumoto, Chem. Lett., 1981, 717.
*Recrystallization of humulene nitrosite from hot ethanol produces both humulene and isohumulene (336) (ca. 1 :1) together with the dinitro-cbmpound (334) and the nitrosite (333). I. Bryson
and J. S . Roberts, unpublished results.
?We prefer the IUPAC numbering (see Editor's note in ref. 172) although we recognise the
preference of Professor Matsumoto and others for humulene numbering based on its derivation
from farnesyl pyrophosphate.
124
accessible humulene-epoxide (340) is treated with LDA to form the allylic alcohol
(341) which is oxidized with Bu'OOH-VO(acac), to give predominantly (342).
Collins oxidation of (342) gives the corresponding epoxy-ketone which on treatment
with hydrazine hydrate and KOH undergoes a Wharton rearrangement to furnish
zerumbol (343) which can be oxidized to zerumbone (338) with MnO,.
As mentioned in previous reports the number of bicyclic and tricyclic sesquiterpenoids which can be derived from humulene (332) has continued to grow
steadily over the past 10 years. Scheme 40 outlines briefly the 17 major structural
types whose biogeneses have been proven or are thought to involve the intermediacy
of humulene. The majority of these sesquiterpenoids have been isolated from
fungal sources, particularly the Basidiomycetes and an excellent review of these
fascinating metabolites has been written by Ayer and Browne.171 In addition to
the challenging synthetic and biosynthetic problems that these metabolites have
presented, another area of considerable interest is the biomimetic conversion of
humulene and its derivatives into the novel skeletons which form the framework of
these compounds. Of particular note is the work of Shirahama and Matsumoto who
have gained considerable success in this area. A full publication from this group172
has now appeared which describes model studies which led to the successful
conversion of the protoilludane epoxide (344) into the two hirsutane derivatives
(345) and (346), the former of which was chemically transformed to hirsutene (347).
It should be noted, however, that all evidence to date indicates that the hirsutanes
are not derived from humulene via the protoilludyl cation but arise by a different
pathway (see Scheme 40 and Vol. 1 1 , p. 39). One of the key compounds used in
humulene biomimetic cyclizations is the 4,5-epoxide (348) which, under acidcatalysed conditions, is able to generate the all important humulen-4-yl cation.
Shirahama and c o - w ~ r k e r have
s~~~
subjected the epoxide (348) to two different sets
of acid conditions. In one case, using trimethylsilyl trifluoromethanesulphonate,
the products are the two africane-type alcohols (349) which had previously been
obtained by reaction of the same epoxide with boron trifluoride e t h e ~ a t e . The
'~~
tetrasubstituted isomer of (349) has been converted into africanol (350) in five
steps. On the other hand, treatment of (348) with boron trifluoride etherate
in acetic anhydride gave the bicyclohumulane derivative (35 1) which was converted
into bicyclohumulenone (352), a naturally occurring compound, in seven steps.
171
172
173
17'
W. A. Ayer and L. M. Browne, Tetrahedron, 1981, 37, 2199.

K. Hayano, Y . Ohfune, H. Shirahama, and T. Matsumoto, Helv. Chim. Acta, 1981, 64, 1347.
H. Shirahama, K. Hayano, Y. Kanemoto, S. Misumi, T. Ohtsuka, N. Hashiba, A. Furusaki
S. Murata, R. Noyori, and T. Matsumoto, Tetrahedron Lett., 1980, 21, 4835.
J. A. Mlotkiewicz, J. Murray-Rust, P. Murray-Rust, W. Parker, F. G. Riddell, J. S. Roberts,
and A. Sattar, Tetrahedron Lett., 1979, 3887.
Sesquiterpenoids
125
-a
cd
22
a
J.
I
126
(344)
(346)
(345)
HO
(347)
-+
(349) R
(356) R
(348)
=H
= AC
(350)
(3 54)
? ..OAc
These two results demonstrate that cyclization of the epoxide (348) has proceeded
from two different conformations of the epoxide, namely the CT conformer (353)
in the absence of a nucleophile to produce (349) while the CC conformer (354)
in the presence of the nucleophilic acetate proceeds to (351). In a subsequent
paper175 it was shown that both conformers (353) and (354) react with boron
trifluoride etherate in acetic acid to give (351) and (355)-(357), the first two
arising from the CC conformer (354) and the second pair from the CT conformer
(353).* Another significant result in this area is the biomimetic-type synthesis of
pentalenic acid (360) from humulene (Scheme 41).176The design of this synthesis
was based on earlier results (Vol. 10, p. 40) concerning the cyclization of the
5-deoxy analogue of (358) and the subsequent conversion of (358) into (359) in 20 %
yield mimics the biosynthesis of the pentalenane sesquiterpenoids (see ref. 183).
The latest result from the Japanese
is the transformation of kumulene to
sterpurene (364), one of the newest additions to the tricyclohumulane family,
vide infra. In this case the results from a previous study (Vol. 10, p. 40) paved
the way for the successful synthesis. Thus, treatment of (361), obtained from
176
177
H. Shirahama, K. Hayano, T. Ohtsuka, E. Osawa, and T. Matsumoto, Chem. Lett., 1981,351.

K. Sakai, T. Ohtsuka, S. Misumi, H. Shirahama, and T. Matsumoto, Chem. Lett., 1981, 355.
Y . Murata, T. Ohtsuka, H. Shirahama, and T. Matsumoto, Tetrahedron Lett., 1981, 22,4313.
*A similar result has been obtained when the epoxide (348) is allowed to react with boron trifluoride etherate in wet diethyl ether. In this case the diol corresponding to the diacetate (351) is
formed exclusively. This diol reverts to the starting epoxide on treatment with PTSA. R. M.
Carman, I. Bryson, and J. S. Roberts, unpublished results.
127
Sesquiterpeno ids
iii
Ho
OH
(358)
Ho
(360)
(359)
Reagents: i, aq. Hg(N03),; ii, KBr; iii, 0,-NaBH,; iv, Cr03-H+; v, NaBH,; vi, Ac,O-py;
vii, PBr,; viii, Am'ONa; ix, Li-EtNH,; x, BF3.Et20;xi, SeO,; xii, Mn0,-KCN-MeOH;
xiii, OH-; xiv, H 3 0 +
Scheme 41
humulene, with boron tribromide gave (362) and (363) both in yields of 20%.
Further reaction of (362) with silver acetate in acetic acid gave sterpurene (364) in
61 % yield The sequence of rearrangements is interpreted in terms of Scheme 42
and this probably represents the actual biosynthetic pathway to the sterpuranes.
As noted above this new class of sesquiterpenoid has emerged recently as
a result of investigations by Ayer et al. on the metabolites of the fungus Stereum
purpureum, the cause of the so-called silver leaf disease common to a number of
fruit trees. In their first paper1'* Ayer et al. established the structures of sterpuric
acid (365), the hydroxy-derivative (366), and the ethylidene acetal (367) by a
combination of chemical and X-ray studies. Further
on this fungus led to
the isolation of sterepolide (368) and dihydrosterepolide (369) both of which are
a .cily,
Br
.*
@
0
I
H '.
OMe
(361)
178
H
(362)
=*..
H :
(363)
W. A. Ayer, M. H. Saeedi-Ghomi, D. Van Engen, B. Tagle, and J. Clardy, Tetrahedron, 1981,
37, 379.
lTP
W. A. Ayer and M. H. Saeedi-Ghomi, Tetrahedron Lett., 1981, 22,2071.
128
(364)
Scheme 42
examples of the rare isolactarane group of which only one other member was known
previously (Vol. 9, p. 116), although another example, merulidial (370), has been
quoted recently.lso The co-occurrence of sterpurane and isolactarane sesquiterpenoids makes the biogenetic relationship shown briefly in Scheme 40 a distinct
possibility. The neutral components of this fungus contain the trio1 (371) and very
interestingly the parent hydrocarbon, sterpurene (364).ls1
(365) R
(366) R
=H
= OH
(367)
CHO
(370)
W. Steglich, Pure Appl. Chem, 1981, 53, 1233.

W. A. Ayer and M. H. Saeedi-Ghomi, Can.J , Chem., 1981, 59,2536.
lEo
lal
129
Sesquiterpenoids
Paquette et ~ 1 have
. accomplished
~ ~ ~ a relatively short synthesis of the methyl
ester of pentalenolactone E (372) (Scheme 43). Full details of the biosynthesis
of pentalenolactone (373) from [ U-13C,J glucose and [6,6-2H2]glucose have been
rep0rted.1~~
These substrates were used in view of the lack of incorporation of
the more conventional acetate and mevalonate isoprenoid precursors. The stereochemical picture which has emerged from this study is that the pentalenane
H
xi, v, xii
Reagents: i, (CH,OH),-PTSA; ii, Bu',AIH; iii, -CH,=CHOEt-Hg(OAc),; iv, 150 "C;

v, H,O+; vi, OMe-; vii, NH,NH,-H,O-Et,N; viii, 1,-Et,N; ix, Ni(CO),-NaOMe; x, CrO,-H+;
xi, MeOMgOCO, Me; xii, CH,O-Et,NH-AcOH
Scheme 43
skeleton is derived from the RSR-CT conformer of humulene (374) (Scheme 44)
which results from attack on the si face of the distal double bond of farnesyl
pyrophosphate. This pathway is consonant with the proven biosyntheses of
fomannosin and the illudins. Cane et al. have further speculated about a possible
enzyme receptor site for humulene formation and subsequent cyclization. In this
work and elsewhere there is the tacit assumption that humulene retains the all-trans
arrangement of the three double bonds prior to cyclization. Models indicate that
this geometric imposition means that Lond formation between C-4 and C-8 may
not be too facile and indeed there is no in vitro example of such bond formation in
humulene chemistry. Examples of C-4-C-8 bond formation are only observed after
18s
L. A. Paquette, H. Schostarez, and G. D. Annis, J . Am. Chem. Soc., 1981, 103, 6526.
D. E. Cane, T. Rossi, A. M. Tillman, and J. P. Pachlatko, J. Am. Chem. Soc., 1981, 103, 1838.
130

H+
(374)
(373)
Scheme 44
C-1 and/or C-2 have been converted to sp3 geometry. One possible explanation for
this apparent anomaly is to invoke a
trans+cis isomerization in humulene
prior to cyclization. This permits a more favourable interaction between a developing cationic centre at C-4 and the ABlg double bond. Thus the conformer (375)
of isohumulene could serve as a precursor for the protoilludyl-derived metabolites
while its enantiomer could proceed to the hirsutane sesquiterpenoids.
A l p 2
(375)
The biosynthetic relationship between illudol (379) and fomannosin (380)
has inspired Semmelhack and c o - w o r k e r ~ ~to~ ~aJ ~beautifully
~
constructed
synthesis of the two natural products via the common intermediate (378) (Schemes
45 and 46). This tricyclic compound (378) was obtained by a Diels-Alder reaction
between (376) and the cyclobutene derivative (377). Another photochemically-based
route (Scheme 47) has been used to obtain protoillud-7-ene (381) and several
oxygenated derivatives.la6
Full reports on the syntheses of methyl isomarasmate (382) and the naturally
occurring marasmic acid (383) have appeared.lB7Ja8A second imaginative synthesis of marasmic acid (383) has also been reported (Scheme 48).189Once again
the power of the intramolecular Diels-Alder reaction has played a pivotal role in
F. Semmelhack and S. Tomoda, J . Am. Chem. SOC.,1981, 103,2427.
M. F. Semmelhack, S. Tomoda, and K. M. Hurst, J. Am. Chem. SOC.,1980,102,7567.
H. Takeshita, I. Kouno, M. Iino, H. Iwabuchi, and D. Nomura, Bull. Chem. SOC.Jpn., 1980,
la4 M.
la6
53, 3641.
la'
la8
189
W. J. Greenlee and R. B. Woodward, Tetrahedron, 1980, 36, 3361.

W. J. Greenlee and R. B. Woodward, Tetrahedron, 1980, 36, 3367.
R. K. Boeckman, Jr., and S. S. KO,J . Am. Chem. SOC.,1980, 102, 7146.
131
Sesquiterpenoids
OSiMQ
OSiMe,
>o"
C0,Et
(376)
q OOEt
E t
(377)
EtO OEt
qH qH
v-viii
iii, iv
f---
EtO OEt
EtO OEt
Et0,C
E t d OEt
.MP
H ' K
EtO OEt
H EtO
- uOEt
HY
OH
(379)
Reagents: i, A ; ii, 3A molecular sieves-MeOH; i i i , LiEt,BH; iv, NaH-PhCH,Br; v, LiAIH,;
vi, BuLi-ClPO(NMe,),; vii, Li-EtNH,; viii, Cr0,-py; ix, LDA; x, CO,; xi, H + ; xii, CH,N,;
xiii, PhSeC1; xiv, H,O,; xv, NaAl(OR),H,; xvi, Me,C=O-H+; xvii, H,O+
Scheme 45
the synthetic strategy. Thus, heating the triene (384) gave two tricyclic products
(385) and (386) in the ratio of 1 : l . Compound (385) results from cyclization
via an endo transition state whereas formation of (386) must occur by the usually
disfavoured exo transition state. In the event both adducts could be converted
into marasmic acid (383), Scheme 48 showing the sequence for (385). A similar set
of transformations was effected on (386) and this gave the trans-isomer of (383)
which was converted into the corresponding enol acetate which gave :-liarasmicacid
(383) on hydrolysis.
A full report on the structural determination of the seco-illudalane sesquiterpenoids, the cybrodins, has appeared.lgO These metabolites, which include
cybrodol (387), isocybrodol (388), cybrodal (389), trisnorcybrodolide (390), and
cybrodic acid (391), have been isolated from the bird's nest fungus Cyathus bulleri.
In addition to these compounds, pterosin C (392), previously isolated from Pteridjum ferns, together with broderol (393) and nidulol (394) for which tentative
structures have been put farward, have been isolated. The five compounds (387)l a 0 W.
A. Ayer and R. H. McCaskill, Can. J. Chem., 1981, 59, 2150.
132
i, ii
(378) --+
b,
vii
ButMe,SiOoH
MsO"
(380)
Reagents: i, LiAlH,; ii, 3A molecular sieves-MeOH; iii, MCPBA; iv, H,O+; v, Bu'Me,SiClimidazole; vi, NaBH,; vii, DHP-PTSA; viii, LDA; ix, CH,O; x, PhSeC1; xi, H + ;xii, H,O,;
xiii, CH,=CHOEt-H+; xiv, MsCI-Et,N; xv, HF; xvi, Cr0,-py ; xvii, Bu,NF
Scheme 46
qo
ii-iv
i
M e 0 OMe
Q
H
___,
H
(38 I )
Reagents: i, hv-CH,=C(OMe),; ii, MeMgI; iii, (CH,SH),-BF,; iv Ra-Ni
Scheme 47
---CHO
C0,Me
Sesquiterpenoids
133
Ijr
C0,Me
q;
qoAc
liv, v
J.
2-
(mOl2!7Q
Me0,C
C02Me
Vlll
Me02C
G
xi
xii, ii
t---
Me02C
Jxiii
CHO
fi
-*...;
Me0,C
OH
0
(3183)
Reagents: Ph,P=CBrCO,Et ; ii, Bu',AlH; iii, Ni(CO),-NaOMe; iv, AcC1-py ; v, H 3 0 + ;
vi, NaH; vii, 200 "C; viii, KOBu'; ix, PTSA-MeOH; x, MsC1-Et,N; xi, DBU; xii, PhSeBrMeOH; xiii, MCPBA: xiv, BBr,
Scheme 48
OH
(387) R1= Me, R2 = CH20H
(388) R1= CH,OH, R2 = Me
(391) R1= Me, R2 = C02H
(389)
(390)
134
OH
'10'
(392)
(394)
(393)
(39 1) have all been synthesized as reported earlier.lgl The seco-illudane, hypacrone
(396) has been synthesized (Scheme 49) from the intermediate (395) previously used
in illudin syntheses.lg2
I
so
+
i
0 0
+
ii
a
(395)
H
0
iii, iJiv
Reagents: i, A ; ii, MeLi; iii, Me,CO-PTSA; iv, hv
Scheme 49
A number of new lactarane sesquiterpenoids have been identified from Lactarius

scrobiculatus ; these include furoscrobiculin A (397), furanether A (398), furanether
lg1
lg2
W. A. Ayer and R. H. McCaskill, Can. J. Chem., 1981, 59, 2159.

F. Sakan, Y. Minami, H. Shirahama, and T. Matsumoto, Bull. Chem. SOC.Jpn., 1981,9,2235.
135
Sesquiterpenoids
B (399), furoscrobiculin B (400), furoscrobiculin C (401), furoscrobiculin D (402),

and lactaroscrobiculide B (4O3).lg3
Continued interest in the synthesis of hirsutane sesquiterpenoids has again
been witnessed during the year under review. In this context, the previously
reported synthesis of hirsutene (347) together with related model studies
has been published in full.194Little and Mullerlg5have also achieved a synthesis
of hirsutene (347) using their previously recorded strategy of intramolecular diyl
trapping to construct the tricyclopentanoid ring system from (404) (Scheme 50)
CO,Me
&
A
j i , iii
bi,
v, vii
(347)
Reagents: i, A; ii, LiAlH,; iii, Bu'Me,SiCl-imidazole; iv, BH,; V, PCC; vi, Bu,NF; vii, (Ph,P),
RhCl; viii, NaOMe-EtOCHO; ix, BuSH-PTSA; x, K0Bu'-MeI; xi, OH-; xii, Ph,P=CH2
Scheme 50
(see Vol. 11, p. 48). The latest synthesis of h i r s ~ t e n e l ~is~remarkable

*'~~
(Scheme 51)
and it is very unlikely that any computer-assisted retrosynthetic analysis would have
come up with this route which involves a photochemical-thermal metathetic
sequence. Thermolysis of the pentacyclic dione (405) gave the cis-syn-cis isomer
(406) which at 310 "C produced an equilibrium mixture of (406)-(408) in the ratio
of 14:49 :37. The requisite cis-anti-cis bisenone (408) was taken through to (409)
which had previously been converted into hirsutene.
' Full details of the total synthesis of the more complex hirsutane sesquiterpenoids
coriolin (410) and coriolin B (41 1) have been p ~ b 1 i s h e d .Another
l~~
route to hirsutic
R. Battaglia, M. De Bernardi, G . Fronza, G. Mellerio, G . Vidari, and P. Vita-Finsi, J . Nur.
Products, 1980, 43, 319.
lo4 T. Hudlicky, F. J. Koszyk, T. M. Kutchan, and J. P. Sheth, J. Org. Chem., 1980, 45, 5020.
lS5 R. D . Little and G. W. Muller, J . Am. Chem. Soc., 1981, 103, 2744.
lg6 G . Mehta and A. V. Reddy, J. Chem. SOC.,Chem. Commun., 1981, 756.
I g 7 K. Taksuta, K. Akimoto, and M. Kinoshita, J . Am. Chem. SOC.,1979, 101, 6116.
19* S. Danishefsky, R. Zamboni, M. Kahn, and S. J. Etheredge, J . Am. Chem. Soc., 1981. 103,
lg3
3460.
136
vii, viii
___,
1
0-7
Jix, x
f-xi
H..'
9
H:'
MeS,CO
0-7
OMe
(409)
(347)
Reagents: i, A ; ii, hv; iii, 500 "C; iv, 310 "C; v, H2-Pd/C; vi, KOBut-MeI; vii, NaBH,; viii,
MeOCH,C1-Pri2NEt; ix, LiAlH,; x, NaH-CS,-MeI; xi, Ref: 197
Scheme 51
H OH
H OH
"OH
(410)
(411)
acid (413) (Scheme 52) has been described;lg9this terminates at the keto-ester (412),
have described a photoa key intermediate to hirsutic acid.200Pattenden et
2oo
M. Yamazaki, M. Shibasaki, and s. Ikegami, Chem. Lett., 1981, 1245.

H. Hashimoto, K. Tsuzuki, F. Sakan, H. Shirahama, and T. Matsumoto, Tetrahedron Lett.,
201
J. S. H. Kueh, M. Mellor, and G. Pattenden, J. Chem. SOC.,Perkin Trans. I , 1981,1052.
lee
1974, 3745.
137
Sesquiterpenoids
kv
H
(4 13)
Reagents: i, TosNHNH,; ii, NaOMe; iii, F-; iv, DHP-H+; v, aq. NBS; vi, Bu,SnH; vii, PCC;
viii, Ph,P=CH2; ix, MeOCH: ;x, H,O+; xi, HC1-MeOH; xii, CrO,H+; xiii, CH,N,; xiv,
NaH-CH,=CHCH,Br ; xv, PdC1,-0,; xvi, KOBu'; xvii, Ref. 200
Scheme 52
chemically-based route to the tricyclopentanoid nucleus. Thus irradiation of the

dicyclopent-1-enylmethane, (414) in methanol produced (416) through the intermediacy of the [2 + 21 addition product (415). Compound (416) has the cis-syn-cis
stereochemistry which limits its synthetic potential for the hirsutane sesquiterpenoids.
The precursor of the marine-derived capnellane sesquiterpenoids is precapnelladiene (417). The epimer (418) of this compound has been synthesized by a
route (Scheme 53) which involves an intial intramolecular photocyclization
138
OMe
+
OCOPh
OCOPh
pi,viii
@xii, xiii
t
xi, iv
f-ix, x
0
(418)
Reagents: i, Li-NH3; ii, Bu'Li; iii, MeCH(I)(CH,),CH=CH,; iv, H,O+; v, PhCOC1-py;

vi, hv; vii, LiN(SiMe,),-MeI; viii, OH-; ix, (CH,OH),H+; x, LiAlH,; xi, POCl,-py; xii,
Ph,F'=CH,; xiii, RhCl3*3H20
Scheme 53
(420)
Reagents: i, LiAlH,; ii, PCC; iii,
(419)
; iv, MeO,CN=NCO,Me;
v, KO,CN=NCO,KAcOH; vi, KOH; vii, K,Fe(CN),; viii, A ; ix, B2H,; x, H,O,-OH-, xi, PPh,=CH,
Scheme 54
followed by a retroaldolization to construct the bicyclo[6,3,0]undecane framework.202Two syntheses of A9$l2-capnellene

(420) have been recorded. The first of
202
A. M. Birch and G. Pattenden, J . Chem. SOC.,Chem. Commun., 1980, 1195.
Sesquiterpenoids
139
these (Scheme 54)203is another nice example of the synthetic utility of intramolecular
1,3-diyl trapping reactions developed by Little. In this particular case the stereoselectivity of the ring closure of the intermediate cyclopenta-1,3-diyl (421) is
not as great as in other examples and this may be the result of an unfavourable
interaction between the hydrogen and the methyl group in (421). This interaction
may be responsibfe for the significant formation of the cis-syn-isomer of (419).
The second synthesis of (420) involves a stereocontrolled construction of the
triquinane nucleus (Scheme 55). 204
I vi
(420)
Reagents: i , CH,=CHMgBr; ii, MnO,; iii, P20,-MeS0,H; iv, Me,CuLi; v, LiC=CH;
vi, HC0,H-H,SO,; vii, CH,=CHMgBr-Cul; viii, 0,; ix, Me,S; x, HC0,H; xi, KOH;
xii, H,-Pt; xiii, PPh,=CH2
Scheme 55
p
p...
HO-
(423)
(424)
(425)
(426)
R, R2= CH,
R = R2= H
R1= Me, R2= OH
R = CH,OH, R2= H
Alliacolide (422) is a new fungal sesquiterpenoid with a unique carbon skeleton

isolated from Marasmius alliaceus. Its absolute stereochemistry (422) has been
determined by a series of circular dichroism measurements of degradation products
203
204
R. D. Little and G . L. Carroll, Tetrahedron Lett., 1981, 22, 4389.

K. E. Stevens and L. A. Paquette, Tetrahedron Lett., 1981, 22, 4393.
140
p p --p
(428)
(429)
(430)
in comparison with related

Other metabolites from this fungus have
been identified as alliacolide I1 (423), 12-hydroxydehydroalliacolide(427), 12noralliacolide (424), 1 1 - and 12-hydroxyalliacolide (425) and (426) respectively,
and alliacide (428).206The biosynthesis of this unique group of sesquiterpenoids
has been investigated207and as a result of feeding experiments with [1-13C]- and
[1 ,2-13C,]-acetate and isolation of the labelled alliacolide, the pattern shown
in (429) could be deduced from the 13C n.m.r. spectra. This means that the three
isoprenoid fragments in the alliacane carbon framework can be dissected as shown
in (430). Further feeding experiments208are under way to elucidate more details
of the biosynthesis which may in fact indicate a cadinane-based route to the
alliacanes.
11 Germacrane
One of the most significant findings this year has been the isolation and identification of (-)-helminthogermacrene (431) from Helminthosporium s a t i v ~ m . ~ ~ ~
(434)
Previously Arigoni2I0had put forward an elegant stereochemical argument for the
co-occurrence of (-)-longifolene (432) and (-)-sativene (433) from this fungus, as
summarized in Scheme 56. The detection of (431) in the mycelium adds substantial
support to this proposal since it is the very ten-membered ring intermediate en route
to (-)-sativene. The final verification of the structure of (431) was achieved by
carbanionic cyclization of the cis,trans-farnesyl sulphide (434) followed by reductive
removal of the sulphide group and dehydration of the derived tertiary alcohol.
6p-Hydroxygermacra- 1(1 0),4-diene (435) has been isolated from various
Verbesina species as the corresponding coumaroyl and feruloyl esters.s0(-)-Mint205
206
207
208
208
210
A. P. W. Bradshaw, J. R. Hanson, D. N. Kirk, and P. M. Scopes, J. Chem. SOC.,Perkin Trans.

1, 1981, 1794.
I. W. Farrell, T. G. Halsall, V. Thaller, A. P. W. Bradshaw, and J. R. Hanson, J . Chem.
SOC.,Perkin Trans. 1 , 1981, 1790.
A. P. W. Bradshaw, J. R. Hanson, and I. H. Sadler, J. Chem. SOC.,Chem. Commun., 1981,631.
J. R. Hanson, Pure Appl. Chem., 1981,53, 1159.
R. E. K. Winter, F. Dorn, and D. Arigoni, J. Org. Chem., 1980, 45, 4786.
D. Arigoni, Pure Appl. Chem., 1975, 41, 219.
141
Sesquiterpenoids
(433)
sulphide (436), a novel sesquiterpenoid from peppermint oil, has been synthesized
by irradiation of f -)-germacrene D (437) in the presence of sulphur.211Treatment
of the methyl sulphonium salts of mintsulphide (438) and isomintsulphide (439)
with LDA gives the homologous sulphides (440) and (441) respectively by way
of a [2,3] sigmatropic rearrangement of the corresponding sulphonium ylides.212
(435)
211
z*a
(437)
K. Takahashi, S. Muraki, and T. Yoshida, Agric. Biol. Chem., 1981, 45, 129.
T. Uyehara, T. Ohnuma, T. Saito, T. Kato, T. Yoshida, and K. Takahashi, J. Chem. SOC.,
Chem. Commun., 1981, 127.
142
On the other hand, reaction of (438)with methyl-lithium gives predominantly (442)

and (443) via the diradical (444),whereas similar treatment of (439)gives largely
(445).
Reduction of the photo-adduct (446) derived from ( +)-isopiperitone and

cyclobutene- 1-carboxylic acid with NaCNBH, gives the lactone (447).Thermolysis
of this compound affords the 6ol-epimer of isoaristolactone (448)and the elemanolide
(449).213
A novel approach to the synthesis of germacranes involves the thermal
opening of a bridgehead cyclobutene which, in turn, is derived by an oxy-Cope
rearrangement (Scheme 57).214
iiii
Reagents: i, hv-CH,=C=CH,;
ii, CH,=CHMgBr; iii, K H ; iv, 180 "C; v, h v
Scheme 57
In an effort to mimic the proposed cyclization of the gernacr-idienyl cation

(450) to the cadinane skeleton, It8 et aL215have examined the fate of the four
hedycaryol phenyl sulphides (451)-(454) on reaction with methyl iodide (cf.
Vol. 10, p. 51). In all four cases the products derived (455)-(462) were eudesmane
derivatives and this finding has been explained in terms of HI-induced cyclizations, the HI being generated from the initially formed sulphonium salts. De-
OH
213
214
216
G. L. Lange, S. So, M. Lautens, and K. Lohr, Tetrahedron Lett., 1981, 22, 311.
S. L. Schreiber and C. Santini, Tetrahedron Lett., 1981, 22,4651.
M. Kodama, K. Shimada, and S. It6, Tetrahedron Lett., 1981, 22, 1523.
Sesquiterpenoids
143
WH+
SPh
sulphurization of (459) gave the ether (463), a defence pheromone of Amitermes

evuncifer. As an alternative approach to the cation (450),216the diol(464) has been
obtained by a [2,3] sigmatropic shift of the sulphoxides (465) and (466) derived
from (451) and (452) respectively. Treatment of the diol with various acids gave
o.-r
PhSO
(465)
(464)
(463)
qqq
HO
&
(OH
PhSO
OH
(466)
Rlp2
OH
(467)
OH
(468)
OH
(469) X1= Me, R2= OH
(470) R1= OH, R2= Me
varying yields of the cadinane-type compounds (467)-(470). In another interesting

transannular cyclization study, the germacradiene (472), derived from (47 1) on
thermolysis, has been subjected to treatment with acetic acid in thiophen01.~~~
ala
M. Kodama, K. Shimada, T. Takahashi, C. Kabuto, and S. It6, Tetrahedron Lett., 1981, 22,
427 1.
m7 J.
R. Williams, J. F. Callahan, and J. F. Blount, J . Org. Chern., 1981, 46,2665.
144
Me0,C
(471)
PhS
PhS
Me0,C
(473) R1= H, R2 = C0,Me

(474) R' = C0,Me; R2 = H
HO
(475)
(476)
Four products (473)-(476) resulted from this reaction, three of which are of the
eudesmane class while the fourth has the cadinane skeleton.
Treatment of the truns,truns-germacranolide, epitulipanolide (477) and two of its
derivatives with selenium dioxide and t-butyl hydroperoxide gives the melampolidetype alcohol (478).21sA mechanism for this allylic oxidation with inversion of
configuration at the AIJo double bond is proposed. It should be noted, however,
that this is not the first report of such a process (cf Vol. 1 1 , p. 55).
(477)
(478)
The isolation and identification of germacrane lactones from a host of plant
sources is an area of continuing interest particularly in the laboratories of Professors Herz and Bohlmann. The search for biologically active compounds and the
chemotaxonomic classification of plant species are the two major driving forces
for this research. The sub-division of these lactones into germacranolides (479)-
JV
0
(479)146Costunolide
Derivative
218
Po
..--0
AcO
OAc
(480)219Artemisiifolin Diacetate
M. Haruna and K. Ito, J . Chem. SOC.,Chem. Commun., 1981, 483.
Sesquiterpenoids
145
(482)220Eupatolide Derivatives
(48 1)2m Tithifolin Derivatives
various R1and R2groups
w
o
..--0
H and OAc
CH,OH
co-occurs
with
OR2
R1O
(483)221R1 =
Cc,
R2
co
=H
CH20H
(484)22
etc.
Artemisiifolin Derivatives
(485)222R
= AC
Ovatifolin (also R
H)
&-+(
QR
- .
mg;ws
0
(486)223Blainvilleolide
Derivatives
various R goups
and
0
(487)2234,5-cis-Acanthospermolide
Derivative
&
0
(488)223Acanthospermolide
Derivative (also 1,lO-epoxide)
146
(524),14s9219-243heliangolides (525)-(563),5p6y118J509244-257 melampolides (564)(566),2589259and cis,&-germacranolides (567)--(580)2407260-264

is in most cases
21*
220
221
222
223
225
F. Bohlmann, C. Zdero, H. Robinson, and R. M. King, Phytochemistry, 1980, 19, 2473.

F. Bohlmann, J. Ziesche, H. Robinson, and R. M. King, Phytochemistry, 1981. 20, 267.
F. Bohlmann, J. Jakupovic, H. Robinson, and R. M. King, Phytochemistry, 1981, 20, 109.
M. Hoeneisen, M. Sicva, and F. Bohlmann, Phytochemistry, 1980, 19,2765.
F. Bohlmann, J. Ziesche, R. M. King, and H. Robinson, Phytochemistry, 1981, 20, 263.
F. Bohlmann, P. Singh, N. Borthakur, and J. Jakupovic, Phytochemistry, 1981, 20, 2379.
F. Bohlmann, A. Suwita, J. Jakupovic, R. W. King, and H. Robinson, Phytochemistry, 1981,
20, 1649.
228
228
229
W. Herz and N. Kumar, Phytochemistry, 1981, 20, 1339.

W. Herz, S . V. Govindan, and N. Kumar, Phytochemistry, 1981, 20, 1343.
F. Bohlmann, C. Zdero, R. M. King, and H. Robinson, Phytochemistry, 1981, 20, 1069.
F. Bohlmann, A. K. Dhar, J. Jakupovic, R. M. King, and H. Robinson, Phytochemistry, 1981,
20, 1077.
F. Bohlmann, J. Jakupovic, R. M. King, and H. Robinson, Phytochemistry, 1981, 20, 1613.

232 W. Herz and S . V. Govindan, Phytochemistry, 1981, 20, 1740.
233 F. Bohlmann, C. Zdero, H. Robinson, and R. M. King, Phytochemistry, 1981, 20, 2029.
234 A. G. Gonzalez, J. Bermejo, F. Toledo, and L. R. Daza, Phytochemistry, 1981, 20, 1895.
235 U. Rychlewska, J . Chem. SOC.,
Perkin Trans. 2, 1981, 660.
236 M. J. Begley, L. Crombie, W. M. L. Crombie, A. K. Gatuma, and A. Maradufu, J . Chem. Soc.,
Perkin Trans. 1, 1981, 2702.
237 A. Rustaiyan, L. Nazarians, and F. Bohlmann, Phytochemistry, 1980, 19, 1230.
238 R. N. Baruah, R. P. Sharrna, G. Thyagarajan, W. Herz, S . V. Govindan, and J. F. Blount,
J. Org. Chem., 1980, 45,4843.
239 B. A. Nagasampagi, U. G. Bhat, F. Bohlmann, and C. Zdero, Phytochemistry, 1981,20,2031.
241 F. Bohlmann, R. K. Gupta, J. Jakupovic, H. Robinson, and R. M. King, Phytochemistry, 1981.
20, 1609.
242 K. K. Purushothaman, S . Vasanth, P. J. Cox, J. A. Akinniyi, J. D. Connolly, D. S.Rycroft, and
G. A. Sim, J . Chem. Res. ( S ) , 1981, 374.
243 K.-H. Lee, T. Ibuka, H. Furukawa, M. Kozuka, R.-Y. Wu, I. H. Hall, and H.-C. Huang,
J. Pharm. Sci., 1980, 68, 1050.
244 W. Herz and N. Kumar, Phytochemistry, 1981, 20, 93.
245 0. Spring, K. Albert, and W. Gradrnann, Phytochemistry, 1981, 20, 1883.
240 F. Bohlmann and C. Zdero, Phytochemistry, 1981, 20, 2431.
247 F. Bohlmann, R. K. Gupta, J. Jakupovic, R. M. King, and H. Robinson, Phytochemistry,
1981, 20, 1635.
248 M. Hoeneisen, M. Kodama, and S . It8, Phytochemistry, 1981, 20, 1743.
250 F. Bohlmann, J. Jakupovic, M. Ahmed, M. Grenz, H. Suding, H. Robinson, and R. M. King,
Phytochemistry, 198 1, 20, 113.
251 F. Bohlmann, C . Zdero, R. M. King, and H. Robinson, Phytochemistry, 1980, 19, 2663.
.d52 C. Zdero, F. Bohlrnann, H. Robinson, and R . M. King, Phytochemistry, 1981, 20, 739.
264 C. A. Bevelle, G. A. Handy, R. A. Segal, G. A. Cordell, and N. R. Farnsworth, Phytochemistry,
1981,20, 1605.
stis P. K. Chowdhury, R. P. Sharma, G. Thyagarajan, W. Herz, and S . V. Govindan, J . Org. Chem.,
1980, 45,4993.
zs8 F. Bohlmann, U. Fritz, R. M. King, and H. Robinson, Phytochemistry, 1981, 20, 743.
267 F. Bohlmann, J. Jakupovic, A. K. Dhar, R. M. King, and H. Robinson, Phytochemistry, 1981,
20, 843.
258 X. A. Dominguez, R. Villarreal, R. Franco, and F. Bohlmann, Phytochemistry, 1981,20, 1431.
268 F. Bohlmann, J. Jakupovic, A. K. Dhar, R. M. King, and H. Robinson, Phytochemistry, 1981,
20, 1081.
280 W. Herz, S . V. Govindan, and J. F. Blount, J . Org. Chem., 1981, 46, 761.
J. W. Klimash and N. H. Fischer, Phytochemistry, 1981, 20, 840.
262 P. L. Cowall, J. M. Cassady, C.-J. Chang, and J. F. Kozlowski, J. Org. Chem., 1981, 46, 1114.
F. Bohlmann, C. Zdero, R. M. King, and H. Robinson, Phytochemistry, 1981, 20, 518.
264 F. Bohlmann, L. Miiller, R. K. Gupta, R. M. King, and H. Robinson, Phytochemistry, 1981,
20, 2233.
230
231
147
Sesquiterpenoids
bAC
(489)224Marginatin
(490)225Vautheriol Derivatives
Derivative
various R groups
HR
o..;
q 9 3 O
OH
HO'.
0
(491)226Eupaserrin
(492)2261 1 PH-Dihydrochamissonin
Derivative
(OAc
' 04
0
(493)227Eupaserrin
(494)228Costunolide Derivatives
Derivative
various R groups
q
:
0
0
= H and OH
Acanthospermolide
Derivatives
(495)22sR
(496)228Ovatifolin
(497)228Grazielia Acid
Derivative
QCAC
0
'0
(498)22s8~-Angeloyloxy-grazielolide (499)229Disyfolide
(and angelate epoxide)
(500)229 Disyhamifolide
148
R3
(501)230Costunolide
Derivatives
(various R1,R2,R3groups)
(502)231Haageanolide
Angelate
QH
A
0
0
(503)231Zinangustolide
(also 1 18, 13-dihydro derivative)
(504)232Scandenolide
AcO
HO
(505)233Costunolide
Derivative
(506)234Arbutifolin
(and 11p, 13-dihydro derivative)
(507)235
(508)236Cordifene 48, I 5-oxide

(cf. Ref. 237)
(509)236Cordifene
,,
(5
Ineupatolide
Sesquiterpenoids
149
. ..-so
R 0
0
AcO
R
(512)238R
(51
= MeBu, Ineupatorolide A
= Ang, Ineupatorolide B
qp
0
( 5 1 3)239
I;I
I;I
*fp
..-so
..--0
see also H --. ? - & y o
OAng
(5 14)240Laurenobiolide
Derivative
I:.:"'?:"
( 5 16)240
gQ
I
OAc
0
(5 17)241Ereglomerulide
H-
OH
(5 15)240Onoseriolide
Derivatives
O
'OAng
A c
HO
0
( 5 18)2412,3-truns-Ereglomerulide
OAc
0
(51 9 y 1 Ereglomerulide
Derivative
---OH
0
(520)242Vicolide B
(521)242Vicolide C
---OR
0
(522)243R
(523)243R
= COC(Me)=CH,, Molephantin
= Tig, Molephantinin
0
(524)243Phantomolin
150
a*
OTig
HO
--.-
0
(525)5 3u- and 3P-H ydroxybejaranolide
OH
,OAc
co-occurs
with
0
(526)5 Atripliciolide
Derivative
gr:c OAc
'
04
0
(527)5 4,5-trans-Bejaranolide
(R = H)
(528)j 3u-Hydroxy-4,5-transbejaranolide
(R = OH)
HO--. -
0
(529)6 1-epi-NiveusinC
Acetate
HO
eacr
0
(531)11*Trichogoniolide
0
(530)11*Atripliciolide
Derivatives
(various R1 and R2groups)
"p::lt
eacr
0
(532)11*Isotrichogoniolide
?R'
O-S
0
(533)11*Trichosalviolide
Derivatives
(various R1 and R2 groups)
0
(534)11*Zexbrevanolide
Derivative
151
Sesquiterpenoids
mo
0
OAng
pgJ
OH
R--
(535)150 Lychnopholide
0
(536)244Niveusin C
(= A n n ~ i t h r i n ~ ~ ~ )
R=OH
=H
(537)244R
(538)244R1 = R2 = OH
(539)244R1 = OH, R2 = H
AcOQ g -
(540)246
go%
-
0
(542)24*
(541)247Heliangin
3-Acetate
(543)249Budlein
Derivative
(544)249
0
(546)250Viguestenin
Derivatives
(545)249Ovatifolin
Derivative
152

0
Q(Tig)
eacr
...-0
(547)251Eremantholanolide
Derivative
(also 4,5-dihydro
derivatives)
(548)251Goyazensolanolide
Derivative
(549)251Zexbrevanolide
Derivative
pp
...-o
(550)252Govazensolanolide
Deiivative
....0
OH
0
(55 1)252 Eremantholanolide
Derivative
(552)253Goyazensolanolide
Derivative
'Q*
.OAng
'
OAc
HO
0
(5 53)253Zexbrevanolide
Derivative
OAng
(554)253
Piptolepolide
HO
bAng \
HO
(555)254 Tsocentratherin
(556)255R
= CO(Me)CH,,
Calaxin
= COCHMe,,
Ciliarin
(557)255 R
0
( 5 1 % ) ~R~ =
~ CO(Me)CH,,
Zexbrevin B
(559)255R = COCHMe,,
Orizabin
Sesquiterpenoids
153
0
(560)256
Atripliciolide
Derivatives
(various R1 and R2 groups)
(also I 1,13-epoxides)
(561)256 Atripliciolide
Derivatives
(various R groups)
Derivative
o:::Q&H
0
(563)257Punctatin
Derivative
Qg
(562)256Atripliciolide
_.--
OAc
0
(564)25s1 1 p, 13-Dihydromelampodin
.OAng
co-occurs
with
HO
0
(565)259Acanthospermolide
Derivative
(566)2594,5-cis-Acanthospermolide
Derivative
CHO
OTig
0
(567)240Wunderolide
(568)260R
(569)260R
=
=
H, Rolandrolide
Ac, Acetoxyrolandrolide
(570)226R = H, Isorolandrolide
(571)260R = Et, Ethoxyisorolandrolide
154
HO
0
(572)261R1= Ac, R2 = CO(Me)=CH,
(573) R1 = Ac, R2 = COCHMe,
(574) R1= Ac, R2 = COCH(Me)Et
(575) R1= COCH(Me)Et; R2= Ac
Melcanthin D
Melcanthin E
Melcanthin F
Melcanthin G
(576)262Piptocarphins A-F
(various R1,R2,R3groups)
HO.
qoA
TigO
OTig
OAc
co-occurs
with
AcO..
(577)263Hirsutinolide
Derivative
(578)263Chrestanolide
.OAc
I~
WAC
O-X,
(579)264Hirsutinolide
(580)264Isohirsutinolide
Derivative
(58 l)2s5 Vernonallenolide
Derivative
(582)4
(583)4
Q;
155
Sesquiterpenoids
..OAc
A c o'0 * - ~ o A c
'0
0
(584)4
0
(585)
relatively straightforward but in other cases rather arbitrary.* The vast majority of
the lactones listed are new, their structures having been deduced by spectral
analysis. In view of the complexity of the structures of these compounds a heavy
reliance on the interpretation of n.m.r. spectra may lead to erroneous conclusions
and indeed some of the compounds listed appear as a result of structural revisions
(particularly of stereochemistry) necessitated by X-ray studies and/or correlations
with proven structures. The newest additions to this group of sesquiterpenoid
lactones are the allenic germacranolides, the vernonallenolides (58 1)-(583),
isolated from several Verrtonia specie^.^^^^^ They co-occur with a number of new
compounds two of which are the glaucolide derivatives (584) and (585).
12 Elemane
Additional examples of elemanolides from a variety of plant sources include
disynaphiolide (586),229 a series of 8-epizinamultifluoride esters (587),231isoarbutifolin (588) and its I 1,13-dihydro derivative,234and (589 ; R = COC(CH,)Me
or R = Tig).266
A full report on the preparation of the photo-adduct (590) from methylcyclobutene and (-)-piperitone and its thermal conversion into the various shyobunones
(59 1) and related sesquiterpenoids has appeared.267Another synthesis of the
cytotoxic compound ( +)-deoxyvernolepin (592) Starting from a-santonin has been
recorded. 268
265
F. Bohlmann, R. K. Gupta, J. Jakupovic, R. M . King, and H. Robinson, Liebigs Ann. Chem.,

1980, 1904.
266
e67
W. Herz and S. V. Govindan, Phytochemistry, 1981, 20, 2229.

J. R. Williams and J. F. Callahan, J . Org. Chem., 1980, 45, 4475.
M. Watanabe and A. Yoshikoshi, Chem. Lett., 1980, 1315.
*Occasionally co-metabolites are included in these structures for convenient referencing.
156
(589)
13 Eudesmane
New additions to the eudesmane family of sesquiterpenoids include (593) and its
1 I, 12-dihydro deri~ative,~
2-desoxyliguhodgonal (594),59and (595)-(601).60J48*269
Herz and Kurnar2'O have reported a compound from another Verbesina species
which may well be identical to the coumarate ester (598). With good reason,
however, they suggest a reversal of stereochemistry at C-4. The costic acid derivative
(602) and its C-7 epimer co-occur with the reynosin derivative (603) in Lasiolaena
s u n t ~ s i i .Huffman
~~~
and Pinder271have expressed some reservations about the
identity of isointermedeol (604) (Vol. 10, p. 70). They have presented evidence
to suggest that the material used may just have been an impure sample of
( +)-intermedeol (605).
In an ongoing study of the constituents of the rare Guyanan tree DuZucia
guianensis, Polonsky et al.272have identified by X-ray analysis the rather unusual
H?
(596)
26B
L70
271
B7a
(597)
(598)
F. Bohlmann, M. Ahmed, R, M. King, and H. Robinson, Phytochemistry, 1981, 20, 1434.

W. Herz and N. Kumar, Phytochemistry, 1981, 20, 247.
J. W. Huffman and A. R. Pinder, Phytochemistry, 1980, 19, 2468.
J. Polonsky, J. Varenne, T. Prange, C. Pascard, H. Jacquemin, and A. Fournet, J . Chem. Soc.,
Sesquit erpenoids
157
p y
OAng
(599) R1= OCinn, R2 = H

(600) R1= H, R2 = OCinn
(602)
P....(
HO,' H
sesquiterpenoid manicoline A (606). A plausible biogenesis of this a-aminotropone

starting from eudesmol has been put forward. The mystery surrounding the
structure of the marine metabolite, cyclaeudesmol, has finally been solved (see
Vol. 10, p. 72) after all the combined efforts to synthesize the four stereoisomers of
the claimed structure (607).273When the last remaining stereoisomer (608) had been
and shown not to be identical to the- natural compound, a more
fundamental structural modification was required. This came about by the isolation
of a compound, originally referred to as isocycloeudesmol, from another marine
source, Luurenciu n i p p ~ n i c aThis
. ~ ~ compound was ultimately shown to be identical
to cycloeudesmol from Chondriu oppositicladu and an X-ray analysis of a derivative
was used to determine the structure as (609) which fits the original n.m.r. data
much better.275
QoH
(608)
87s
274
276
(609)
R. A. Moss and E. Y . Chen, J. Org. Chem., 1981,46, 1466.

M. Ando, S. Sayama, and K. Takase, Chem. Lett., 1981, 377.
T. Suzuki, A. Furusaki, H. Kikuchi, E. Kurosawa, and C. Katayama, Tetrahedron Lett., 1981,
22, 3423.
158
New additions to the eudesmanolide family include (6 10)-(635).105J54922092229

The examination of liverwort species continues to reveal interesting
new structures such as those of ( +)-P-frullanolide (636) and ( +)-brothenolide (637)
from Frullania b r ~ t h e r and
i ~ ~(~+)-crispatanolide (638) from Makinoa ~ r i s p a t a . ~ s ~
The last compound is unique in the eudesmane field having a 8-lactone attached
between C-7 and C-14.
231p247p2499276-282
(61
(61O)lo3Inucrithmolide
Alantolactone
Derivative
Q3$:
(Ac)HO*o
OH(AC)
(6 I 3)154 Eridanolide
Derivatives
(various R groups)
(6 14)220Balchanin
Derivative
qIg
A
(Sen01
n
0
(615j2@Arhsculin
(612)lb4Ivangustin
Derivative
0
(6 1 6)222Arturin
(617)231Ivangustin
Derivative
Derivative
276
A. G . Gondlez, A. Galindo, H. Mansilla, and A. Gutibrrez, Phytochemistry, 1981, 20, 2367.

22,
277
278
27s
280
281
282
283
a84
X. A. Dominguez, R. Franco, G. Cano, R . Villarreal, M. Bapuji, and F. Bohlmann, Phyfochemistry, 1981, 20, 2297.
F. Bohlmann, J. Jakupovic, and A. Schuster, Phytochemistry, 1981, 20, 1891.
B. A. Nagasampagi, J. S. Sohoni, F. Bohlmann, and C . Zdero, Phytochmisfry,1981,20,2034.
F. Bohlmann, A. K. Dhar, J. Jakupovic, R. M. King, and H. Robinson, Phytochemistry, 1981,
20, 838.
F. Bohlmann, J. Ziesche, R. M. King, and H. Robinson, Phytochernistry, 1981, 20, 751.
R. Takeda, Y. Ohta, and Y . Hirose, Chem. Lett., 1980, 1461.
Y. Asakawa, M. Toyota, Z. Taira, T. Takemoto, M. Kido, and Y. Ichikawa, J . Chem. SOC.,
Chem. Commun., 1980, 1232.
Sesquiterpenoids
159
c":I.-
OTig
(618)247
Reynosin Derivative
(619)247A's5 Arbusculin Derivative
(620)247
Balchanin Derivative
(621)249Ivasperin
Derivatives
A39',
..m
OH
-..o 0
H
(622)249
__..
Po.
Ho'
(624)277
(623)276Maritimin
OH
O q Z ? ?
(625)277Ixtlixochilin
Derivatives
(626)278
w
o
Ho/
(627)278Asperilin
Derivatives
q,
0-
(628)279Isoivangustin
(629)280
R1
0'
*.. H
0
(630)280
0
"
0
(631)28'R1= R2= H
Dimerostemmolide
Derivatives
(632) R1= OH, R2 = Ang
(633) R1= OH, R2 = Mebu
160

OAc OAc
q
OR
(634)282Oxidoisotrilobolide
Derivatives
(various R groups)
(635)2s2Trilobolide
Derivatives
(various R groups)
The structure of cc-santonin chlorohydrin (639) has been revised as a result

of an X-ray analysis.285 Further irradiation of photosantonin (640) produces
neophotosantonin (641)286by a [1,5] antarafacial sigmatropic hydrogen migration.
Syntheses of the following eudesmane sesquiterpenoids have been recorded :
(642),2s7 (643),287 (644),287 ( +)-p-cyperone (645),28s P-costol (646),289 arctiol
(647),289and vetiselinenol (648).290The photo-adduct (649), derived from I ,2bis(trimethylsi1oxy)cyclobutene and ( -)-piperitone, has been converted into the
q Eto2c20J
Eto
6H 0
....
....
....
RO
R
2
R
R
l
(642) R' = OH, R2 = H

(643) R' = R2 = H
(644) R' = H, R2 = OH
285
288
287
288
288
2no
(645)
(646)
H. Takayanagi, H. Ogura, and T. B. H. McMurry, Bull. Chem. SOC.Jpn., 1981, 54,1259.

A. W. Burgstahler, J. Org. Chem., 1981, 46, 1741.
F. Bohlmann and H. Kassner, Chem. Ber., 1981, 114, 2415.
J. P. Kutney, J. Balsevich, and P. Grice, Can. J. Chem., 1980, 58, 2641.
S. Torii and T. Inokuchi, Bull. Chem. SOC.Jpn., 1980, 53, 2642.
R. B. Miller and J. M. Frincke, J. Org. Chem., 1981, 46, 2972.
Sesquiterpenoids
161
p..
.,<
eudesmane-type compound (650).291In an approach to the synthesis of polyhydroxyagarofurans, Huffman and Hillenbrand292have repeated the Robinson annelation
of hydroxycarvone with ethyl vinyl ketone. In contrast to an earlier result, the major
product of this reaction is the dione (651), the minor product being the C-10
epimer. Treatment of (651) with MCPBA, followed by LiAlH4reduction and Jones
oxidation of the resultant stereoisomeric 3,9,11-trials gave 9-keto-a-agarofuran
(652). A short synthesis of frullanolide (654) has been achieved, based on a newly
developed nickel-promoted cyclization/carbonylation procedure for the one-step
preparation of a-methylene-y-lactones (Scheme 58).293Both the E- and Z-isomers
Br
+ 2-isomer
(653)
(654)
Reagents: i , MeO,CC(Br)=PO(OEt),; ii, Bu',AlH ; iii, MsCl-Et,N; iv, Ni(CO),
Scheme 58
of (653) gave frullanolide on treatment with nickel carbonyl, presumably by reaction

through a common allyl-nickel intermediate. A rather long but nonetheless
interesting second synthesis of the seco-eudesmanolide eriolanin (656) has been
accomplished (Scheme 59).294The stereocontrolled construction of the substituted
cylohexenone (655) is reminiscent of Still's synthesis of trichodermol (Vol. 11,
p. 18).
291
M. Van Audenhove, D . De Keukeleire, and M. Vandewalle, Bull. SOC.Chirn, Belg., 1981, 90,
255.
292
294
J. W. Huffman and G. F. Hillenbrand, Tetrahedron, 1981, 37, Suppl. No. 1, 269.

M. F. Semmelhack and S. J. Brickner, J . Am. Chem. SOC.,1981, 103, 3945.
M. R. Roberts and R. H. Schlessinger, J . Am. Chern. SOC.,1981, 103, 724.
162
MOMO
OSiMe,But
x-xii
(655)
Jxiii-xvi
MOMOw S i M e z B u t
xvii-xx, ii,
Jxxi, xxii
AcO
AcO
a
OAc
pxV,
OAc
xxvi
HO
HO
HO
0,
But Me,SiO
>xviii,
iv, xxvii,
xix,
xxix, xix
ButMe,SiO
OSiMe,
II
Reagents: i, ClCH,OMe-PhNMe,; ii, KOH; iii, Me,&,; iv, LDA; v, MeCH=CHCO,Me;
vi, Br,; vii, NaBH,; viii, Zn-EtoH; ix, KOBu'; x, LiAlH(OBu'),; xi, Bu'Me, SiC1-imidazole;
xii, aq. NBS-Na,CO,; xiii, Bu',AlH; xiv, MsCI-Et,N; xv, NaI; xvi (CH,=CH),CuLi ;
xvii, Et3NHF; xviii, LiCH,CO,Li; xix , H + ; xx, 0,;xxi, Ac,O-py; xxii, (CH,SH)2-BF3Et20;
xxiii, PCC; xxiv, PhSeCl ;xxv, K,CO,-MeOH ;xxvi, Bu'Me,SiCI-py-then Me3SiC1; xvii, CO,;
xxviii, CH,O-Et,NH ; xxix, (CH,=CMeCO),O-py-DMAP
Scheme 59
Sesquiterpenoids
163
14 Vetispirane and Related Sesquiterpenoids

A new pair of stereochemically different lubimins, 2-epi- and 15-dihydro-2epilubimin (657) and (658) respectively, have been identified as stress metabolites
in potatoes inoculated with Alternaria s o l a ~ l i Another
. ~ ~ ~ new phytoalexin from
potatoes infected with Phytophthora infestans is rishitinone (659) whose structure
is based on spectral data together with the correlation of its dihydro derivative
with the identical compound synthesized from ( +)-nootkatone (660).296An
investigation of the stress compounds from various Nicotiana species infected with
tobacco mosaic virus and tobacco rattle virus has revealed the presence of six
metabolites, solavetivone (661), 3-hydroxysolavetivone (662), solanascone (663),
phytuberin (664), phytuberol (665) and glutinosone (666) in varying amounts.297
None of these compounds are present in the healthy tobacco leaves. By application
of Nakanishis exciton chirality method to the dibenzoate of capsidiol, the absolute
configuration of this stress compound has been shown to be (667) as anticipated on
biogenetic grounds. 2 9 *
(657) R
(658) R
=
=
CHO
CH20H
R
Or&,
(661) R = H
(662) R = OH
(664) R = AC
(665) R = H
HO
A. Stoessl and J. B. Stothers, Can. J. Chem., 1980, 58, 2069.

N. Katsui, F. Yagihashi, A. Murai, and T. Masamune, Chem. Letr., 1980, 1455.
2 @ 7 R. Uegaki, T. Fujimori, S. Kubo, and K. Kato, Phytochemistry, 1981, 20, 1567.
2 9 8 M. J. Stillman, J. B. Stothers, and A. Stoessl, Can J. Chem., 1981, 59, 2303.
IB6
164
(-)-Phytuberin (664) has been the synthetic target for three groups in the
year under review. The first of these (Scheme 60) started from (-)-2-carone
(668).299The second one (Scheme 61), commencing with (-)-carvone (669), is
rather inadequately described.300 For instance, it is claimed that the lithium
i, ii
PhCH,O
OQiii
I
PhCH,O
%
0
I
OCH2Ph
PhCH,?
H;q
PhCH20
&
OCHzPh
OAc
OCH,Ph
C
/
C0,Et
Reagents: i, LDA; ii, PhCH,OCH,Cl; iii, PhCH,OH-PTSA; iv, LiC rCC0,Et; v, Me,CuLi
(-24 "C); vi, H,-Pd/C; vii, Bu',AlH; viii, OH-; ix, Ac,O-Et,N-DMAP
Scheme 60
.1.;,
vii
(672)
(67 1)
Reagents: i, LDA; ii, CH,OH; iii, LiCECH; iv, Ac,O-py; v, HgS0,-aq. MeOH;
vi, EtOC=CLi; vii, (CO,H),--MeOH; viii, MCPBA; ix, LiAIH,; x, 150 "C
Scheme 61
aoo
D. Caine and T. L. Smith, Jr., J. Am. Chem. SOC.,1980, 102, 7570.

J. A. Findlay, D. N. Desai, G. C. Lonergan, and P. S. White, Can. J . Chem., 1980, 58, 2827.
Sesquiterpenoids
165
enolate of (-)-camone reacts with formaldehyde to give (670) plus its C-10
epimer (do the authors mean dihydrocarvone?); no conditions are given for the
conversion of (671) into (672); not a single optical rotation is recorded for any
of the optically active compounds in the synthetic sequence. The final synthesis
(Scheme 62) involves an interesting elaboration of elemol (673) to give the lactone
(674) which had previously been converted into phytuberin (664).301
\\
piv,
ii
Reagents: i, O,-Me,S; ii, AcC1-PhNEt,; iii, NaI0,-OsO,; iv, OH-; v, 0,-NaH;

vi, LiCH,CO,Li; vii, H,O+; viii, Os0,-py; ix, DBU; x, Pb(OAc),; xi, NaBH,; xii, TsC1-py;
xiii, NaBH,CN; xiv, Li-NH,
Scheme 62
Solavetivone (661) has also been a synthetic objective with two new syntheses
having been completed. The first of these (Scheme 63) achieved syntheses of
both solavetivone (661) and the hydroxy derivative (675), whose glucoside has
been identified in
The second synthesis (Scheme 64) relied upon a
Diels-Alder reaction to construct a bicyclo[2,2,2]octyl framework which was then
cleaved by acid to release a prenyl-mesylate (679) for further acid-promoted
301
ao2
F. Kido, H. Kitahara, and A. Yoshikoshi, J. Chem. Soc., Chem. Commun., 1981, 1236.
C. Iwata, T. Fusaka, T. Fujiwara, K. Tomita, and M. Yamada, J . Chem. SOC., Chem.
Cornmun., 1981,463.
166

"
s CHNz
--+
i
---+
i
OH
0
/,iii
CQ,
2=xcyq)toy&
OMS
C0,Et
j,x-xiii
OH
kii
Reagents: i, CuCI,; ii, LiAIH(OBu'),; iii, Li-NH,; iv, (CH,SH),-BF,.Et,O; v, MsC1-py ;

vi, NaCH(CO,Et),; vii, OH-; viii, CH,O-Et,NH; ix, H+-A; x, Bu', AIH; xi, (CI,C),CO-Ph,P;
xii, Zn-HOAc; xiii, Me1
Scheme 63
c y c l i ~ a t i o nIn
. ~ ~the
~ event, conditions were found for the obtention of all four
Diels-Alder a d d u c t ~ ,the
~ ~ syn-endo,exo
~
isomers (676) being transformed to
hinesolone (680) and p-vetivone (68 l), while the anti-endo,exo isomers (677) were
converted into solavetivone (661). In a subsequent communication the same
devised an alternative method (Scheme 65) for the preparation of the
anti-endo- and antfexo-adducts (682) and (683) corresponding to (678). A full paper
on the synthesis of epihinesol (684) (ragarospirol) (see Vol. 2, p. 111) and the
further elaboration of an intermediate to hinesol (685) has been published.306An
interesting new spiro-annelation procedure has been developed which involves
regiospecific intramolecular alkylation of enolates generated by non-hydrolytic
decarboxylation of w-halo-p-keto-esters. Applying this method to the two ketoesters (686) and (687) (Scheme 66) provided a short route to p-vetivone (681) and
p-vetispirene (688) (together with minor amounts of their C-4 e p i m e r ~ ) . ~ ~ '
303
,04
305
306
307
A. Murai, S. Sato, and T. Masamune, Tetrahedron Lett., 1981, 22, 1033.

A. Murai, S. Sato, and T. Masamune, Chem. Lett., 1981, 429.
A. Murai, S. Sato, and T. Masamune, J . Chem. SOC.,Chem. Commun., 1981, 904.
J. Lafontaine, M. Mongrain, M. Sergent-Guay, L. Ruest, and P. Deslongchamps, Can. J .
Chem., 1980,58,2460.
R. G. Eilerman and B. J. Willis, J . Chem. SOC.,Chem. Commun., 1981, 30.
Sesquiterpenoids
167
Reagents : i, Br2-Fe; ii, CH,=CHCH,MgBr ; iii, OsO,-NaIO,; iv, (CH,OH),-PTSA ;

v, Li-NH,-EtOH; vi, 140C; vii, CH,=CHCO,Me; viii, H,O+; ix, NaBH,; x, MeLi;
xi, MsCl-Et,N; xii, HC0,H; xiii, aq. (CO,H),; xiv, Al,O,-py
Scheme 64
168
i-iii
Iv-vii
Hd
H6
(682)
(683)
; v, MeLi; vi, Bu',AlH;
Reagents: i, LDA; ii, ClCH,CN; iii, CH,PPh,; iv

vii, NaBH,
Scheme 65
J,iiiv,
i, ii, v
(687)
(681)
Reagents: i, LiCl-HMPA; ii, MeLi; iii, PTSA; iv, PCC; v, H,O'
Scheme 66
Sesquiterpenoids
169
15 Eremophilane, Ishwarane
Recent additions to the eremophlane sesquiterpenoids include the petasol

derivative (689),308 isofukinone (690),309 the noreremophilane (69 1),310 and the
unique cyclopropenone derivative (692).311 This last compound also co-occurs
q&
qly
0
with its C-7 epimer and the eudesmane analogue (693). A variety of furanoeremophilanes, eremophilanolides, and cacalol derivatives (694)-(706)649312-314 have
been isolated from various Senecio species. Noteworthy are the structures of
the eremophilene derivative (699)312which has the same stereochemistry as capsidiol
(667) and senaequidolide (705),313an oxidized cacalol derivative. An X-ray analysis
of istanbulin-B has shown it to have structure (707).315A variety of seco-eremophi-
&
0
A
RO-*
(694)64various R groups
(695)64R
(696) R
= H,
=0
OH
(697)312
OH
HO
(698)312R
308
308
310
311
H or OH
***
(699)312
(700)313
F. Bohlmann, M. Ahmed, H. Robinson, and R. M. King, Phytochemistry, 1981, 20, 1157.

F. Bohlmann and U. Fritz, Phytochemistry, 1980, 19, 2471.
F. Bohlmann, W. Kramp, H. Robinson, and R. M. King, Phytochemistry, 1981, 20, 1739.
F. Bohlmann, J. Jakupovic, L. Muller, and A. Schuster, Angew. Chem., Int. Ed. Engl., 1981,20,
292.
314
F. Bohlmann and J. Ziesche, Phytochemistry, 1980, 19, 2681.

J. Jizba, V. LaudovA, Z . Samek, K. Ubik, and L. Novotny, CON.Czech. Chem. Commun., 1981,
315
46,1048.
P. J. Cox, F. Hall, and G. A. Sim, Tetrahedron, 1980, 36, 3437.
313
.*
170
@&AngO...(y&
OMe
R.
OH
(701)313
OR
(703)313various R groups
(702)313
OMe
HO
(705)313
Senaequidolide
(706)314Nemosenin
(704)313
lanolides (708) have been identified in Senecio r n a ~ r o t i s .The

~ ~ ~conformational
equilibria of a number of furanoeremophilanes have been studied by lH, 13Cn.m.r.,
and c.d.
These compounds exist in steroid-like conformations
(709) and non-steroid-like conformations (7 10) according to such factors as nature
of substituents, nature of solvent, and concentration, etc.
mo
(707)
OAc
( J OR
Y k o
(708)
A very neat method for the synthesis of furanoeremophilanes has been devised
which incorporates a so-called bis-heteroannulation process.31sThis is achieved
by an intramolecular Diels-Alder reaction between an oxazole and an acetylenic
grouping and is nicely demonstrated by the synthesis of ligularone (711) and
petasalbine (7 12) (Scheme 67).319 A number of straightforward syntheses of
316
317
s18
81B
F. Bohlmann, R. K. Gupta, J. Jakupovic, R.M. King, and H. Robinson, Phytochemistry, 1981,

20, 1155.
M. Tada, T. Sato, T. Takahashi, K. Tori, I. Horibe and K. Kuriyama, J . Chem. SOC.,Perkin
Trans. 1, 1981, 2695.
P. A. Jacobi, D. G. Walker, and I. M. A . Odeh, J . Org. Chem., 1981, 46, 2065.
P, A. Jacobi and D. G . Walker, J. Am. Chem. Soc., 1981, 103,461 1.
Sesquiterpenoids
171
(7 12)
Reagents: i, MCPBA; ii, LiCH,NC; iii, Me,SO-(COCl),; iv, LiCzCMe; v, A
Scheme 67
R2
HO
(713) R1= R2 = H
(714) R1= Ac, R2= H
(715) R1= Bu', R2= H
(716) R1= Pr; R2= OPr
J$Jq
(7 19)
172
eremophilane sesquiterpenoids include those of 6P-hydroxy-1,lO-dehydrofuranoeremophilan-9-one (7 13),320decompositin (714),320adenstylone (715),320 dihydrodecompositin (7 17),3203 ~,6~-dipropionyloxyeuryopsin-9-one
(7 16),320eremofortin
B (7 18),321 furanoeremophilan-3,6-dione (7 19),322and furanoeremophilan-6a, 14olide (720).322The unusual seco-furanoeremophilanes (72 1)323 and (722)324have also
been synthesized.
The biosynthesis of PR toxin (723), derived from Penicillium roqueforti, has
been examined by incorporation of [ 1,2-13C2]acetateinto the fungus.325 The
labelling pattern as observed from the I3C n.m.r. spectrum is completely in accord
with the original Robinson proposal involving a C-10, C-5 methyl migration from a
eudesmane-type precursor, as has been demonstrated before.
A new type of seco-ishwarane alcohol (724) has been identified in the roots
of A ristolochia i ~ d i c aThis
. ~ ~compound,
~
which co-occurs with ( +)-led01 (725),
has antifertility properties when tested on mice. Its structure was deduced on the
basis of spectral analysis together w.ith its correlation with a derivative of ishwarane
(726). A full report on the synthesis of ishwarone (727) has been presented.327
(723)
(726) R
(727) R
=
=
H2
0
16 Guaiane, Pseudoguaiane, Patchoulane, Seychellane

The new guaiane alcohol (728) has been identified in the soft coral Nephthea
~ h a b r o l i i . The
~ ~ * vast majority of new guaiane sesquiterpenoids are guaian-6a, 12elides and these are listed in the Table.61,152,224,228,230,231,233,241,242,251,329-33 9 In
320
321
322
323
324
325
K. Yamakawa and T. Satoh, Heterocycles, 1981, 15, 337.

K. Yamakawa, T. Mashiko, and T. Satoh, Chem. Lett., 1981, 929.
M. Tada, Y. Sugimoto, and T. Takahashi, Bull. Chem. SOC.Jpn., 1980, 53, 2966.
F. Bohlmann and G . Fritz, Tetrahedron Lett., 1981, 22, 4803.
F. Bohlmann and G . Fritz, Tetrahedron Lett., 1981, 22, 95.
S. Moreau, A. Lablache-Combier, and J. Biguet, Phytochemistry, 1981, 20, 2339; A. A.
Chalmers, A. E. de Jesus, C. P. Gorst-Allman, and P. S . Steyn, J. Chem. SOC.,Perkin Trans. I,
1981, 2899.
S. C. Pakrashi, P. P. G. Dastidar, S. Chakrabarty, and B. Achari, J . Org. Chem., 1980,454765.

327 E. Piers and T.-W. Hall, Can. J. Chem., 1980, 58, 2613.
328 B. F. Bowden, J. C. Coil, and S. J. Mitchell, A m . J . Chem., 1980, 33, 1833.
328 F. Bohlmann, W. Kramp, R. K. Gupta, R. M. King, and H. Robinson, Phytochemistry,
1981, 20, 2375.
330 A. Rustaiyan, A. Niknejad, C . Zdero, and F. Bohlmann, Phytochemistry, 1981, 20, 2427.
331 E. Tsankova, U. J. Kempe, T. Norin, and 1. Ognyanov, Phytochemistry, 1981, 20, 1436.
332 F. Bohlmann, A. K. Dhar, R. M. King, and H. Robinson, Phytochemistry, 1981, 20, 1144.
333 A. Rustaiyan, L. Nazarians, and F. Bohlmann, Phytochemistry, 1981, 20, 1152.
334 A. Rustaiyan, A. Niknejad, F. Bohlmann, and A. Schuster, Phytochemistry, 1981, 20, 1154.
336 A. F. Halim, A. M. Zaghloul, and F. Bohlmann, Phytochemistry, 1980, 19, 2767.
337 F. Bohlmann, C. Zdero, R. M. King, and H. Robinson, Phytochemistry, 1980, 19, 2669.
338 Y. Asakawa, M. Toyota, and T. Takemoto, Phytochemistry, 1981, 20, 257.
339 Y . Asakawa, Z . Taira, M . Toyota, T. Takemoto, W. Herz, and T. Sakai, J . Org. Chem., 1981,
326
46, 4602.
Sesquiterpenoidr
173
Table Guaian-6q12-olides (1 4 a H stereochemistry unless otherwise stated)

Double bond
position(s)
3,4; 11,13;10,14
Name
Substituents
Ref.
2P,8P-diOH ;
9P-0COC(CH2OAc)==CHMe
Preeupatundin*
3,4;11,13;10,14
2P,9P-diOH ;
8P-OCOC(CHzOAc\-CHMe
3,4;11,13;10,14
Preeupatundin*
2P,9P-diOH ;
8P-OCOC(CHzOH+CHMe
Agriantholide*
3,4;11,13
2/3,9a-diOH;
8P-OCOC(CH2OAc+CHMe ;
1Oa,14-epoxy
4,15;9,10
1 1a-Me
Eremantholide*
4,15;11,13;10,14 3-keto; 8a-OH
Zaluzanin C*
4,15
Zaluzanin C*
3P,8a-diOH; 4a, 11a-diMe
3,4;1,10;11,13
Guaiagrazielolide*
8P-OAng; 9,14-P-lactone
Lasiolaenin*t
3,4;11,13;10,14
e.g. 8P-OTig; 9P-OH
Dehydrocostus lactone" 4,15 ;11,13 ;10,14 9a-0MeBu
Dehydrocostus lactone* 4,15;11,13;lo, 14 9a-Oval i
Dehydrocostus lactone* 4,153 1,13;lo, 14 8cr-OAng
Dehydrocostus lactone* 4,15;11,13;9,10
14-OAng
Zaluzanin C*
3P-OAng; 1la-Me
4,15 ;lo, 14
Jaquilenin*
3,4;1,10
2-keto; 15-OAc; 11P-Me
Estafiatin*
11,13
3a,4a-epoxy; 8a-OAng ; 10a-OH
Vicolide A
3,4;11,13
2-keto; 8a-OH; 9P-OAng; IOP-Me
Cumambranolide*
3,4;11,13
8a-OCOCHMe, ; 1 Ocr-OH
3,4;11,13;1,lO
KauniolideG
3,4 ;11,13 ;10,14
Rupicolin*
2u-OH
3,4;11,13
Arbiglovin*0
2-keto; 10a-OH
1,10;11,13
2-Oxoludartin
2-keto ; 3u,4a-epoxy
10,14
Solstitidin*
3-keto ; 4a-Me ; 1 1or-OAc ; 1 3-OAc
2,3;11,13
la,4a-peroxy; 9a-OAc; 1Oa-OH
Apressin
11,13;1,10
2-keto ; 3a,4a-epoxy ; %-OH ;
Guevariolide
8P-OCOCH=CMez
4,159 1,13;10,14 2,3-diOH ; 8a-OCOC(Me)==CH
Costus lactone*
11,13;10,14
3,4-diOH; 8a-OCOC(CH,0H)-CH2
Acrorepioli de
11,13;10,14
Repin*
3P,8P-diOH; 4p,15-epoxy
3,4;11,13
Spicatin*$
2P-OH ; 8P-X ; 1Oa,14-epoxy
3,4;11,I3
Spicatin*$
2P,lOa-diOH; 8P-X; 1 4 4
10,14
(no name)
3-keto; 4a,l la-diMe; 9p-OH
4,15;1 I , 13;9,10
Eremanthine*
8a-OCOCH2CHMe,
4,15; 1 1,13;10,14 8a-OCOCH,CHMe2
Costus lactone*
3,4;11,13
Cumambranolide*
8a-OCOC(Me)=CH 2 ; 1Oa-OH
3,4;11,13
Cumambranolide*
8or-OTig; 1Ou-OH
11,13;10,14
Estafiatin"
3a,4a-epoxy;8a-OCOC(Me)=CH
3,4;9,10
PorelladiolidelI
2P,14-y-lactone; 1 Icr-Me
Eregoyazidin
9,lO
3-keto; 4a,l la-diMe
Preeupatundin*
61
61
61
61
152
224
224
228
230
23 1
23 1
23 1
23 I
23 1
233
241
242
251
329
329
329
329
330
33 1
332
333
333
334
335
335
336
337
337
337
337
337
338
339
*Derivative of. ?Eight different compounds, four of which have 3a,4a-epoxide. $Also 11p,l3dihydro derivative. SX =
11 Also 3a,4a-epoxy derivative.
15
Q
3
11
13
174
addition to these are the more unusual or modified guaianolides (729)-(744).2309279f

The new pseudoguaianolides are depicted by structures (745)-(758).345-350
3379340-344
(729)230R1= CHO, R2 = H, Lasiolaenolide Derivatives

(730) R1= CH20H, R2 = H
(731) R1= CH20H, R2 = OAC
(732) R1= CHO, R2 = OAc (3a, 4a-epoxide)
(733)279
* IH
(734)337R = H, Elehirtanolide
(735) R = OCOCH,CHMe,
0
(736)340R1 = CH,OH, R2 = Ac, Lactucin Derivatives
(737) R1 = CHO, R2 = COC(Me)=CH,
(also I 1p, 13-dihydro

analogues of (736)
and (738)-Jaquinelin
Derivatives)
343
F. Bohlmann, J. Jakupovic, W.-R. Abraham, and C. Zdero, Phytochemistry, 1981, 20, 2371.
K. Ito and T. Iida, Phytochemistry, 1981, 20, 271.
Z. Samek, T. VanEk, and M. Holub, Coll. Czech. Chem. Commun., 1981, 46, 941.
J. F. Malone, M. Parves, A. Karim, M. A. McKervey, I. Ahmad, and M. K. Bhatty, J . Chem.
344
SOC.,
J. Beauhaire, J. L. Fourrey, J. Y.Lallemand, and M . Vuilhorgne, Tetrahedron Lett., 1981, 22,
340
s41
a4a
2269.
345
346
347
348
349
360
G . Willuhn, G. Pretzsch, and D Wendisch, Tetrahedron, 1981, 37, 773.

W. Herz, N. Kumar, and J. F. Blount, J . Org. Chem., 1981, 46, 1356.
Y. Imakura, K.-H. Lee, D. Sims, R.-W. Wu, I. H. Hall, H. Furukawa, M. Itoigawa, and K.
Yonaha, J . Pharm. Sci., 1980, 69, 1044.
W. Herz, D. Gage, and N. Kumar, Phytochemistry, 1981, 20, 1601.
F. Bohlmann, J. Ziesche, H. Robinson, and R . M. King, Phytochemistry, 1981, 20, 1146.
M. A. ElSohly, A. S . Sharma, and C . E. Turner, J . Nut. Products, 1981, 44, 617.
Sesquiterpenoids
175
(739)341Inuchinenolide B
(740) Inuchinenolide C
Go
and
OAc
,
I
(741) Inuchinenolide A
Q.oAc
---0Ang
q.H
0
0
(742)342Acetylisomontanolide
(743)343Grilactone
0
(744)344Isoabsinthin
(745)345R = OH Chamissonolide
(746) R = H
(747)346R1= R2 = H , R udmollin
(748) R1= Ac, R2 = H Derivatives
(749) R1 = H, R2 = AC
(750)34sRudmollitrin
(751)347Microhelenin A
176
(752)347R
(753) R
(754) R
=
=
=
H, Plenolin
COCH(Me)Et, Microhelenin B
Tig, Microhelenin C
aoQ
;.Q
(755)347Microlenin Acetate
(756)34s3-Hydroxyambrosin Damsinate
(757)349Kingiolide
(758)350Isoheleniamarin
Two stereochemically different sets of bourbonolides (759), (760),4 and (76 1)(763)224have been identified in various Vernonia species. Co-occurring with the
last three is the guaianolide (764). A further examination of Trixis species has
resulted in the isolation of the trixic acid derivative (765) and other examples of
trixikingolides (766) together with the rotundene analogue (767).225Additional
examples of xanthanolides are the tomentosin derivatives (768)-(770)27s and
2-epixanthanol (771).351It is interesting to note that it has been reported that
xanthumin (772) and 8-epixanthatin (773) are potent insect development inhibitors. 352
0
(759) R
(760) R
asl
= Tig
=
COC(Me)=CH,
F. Bohlmann and C . Zdero, Phytochernistry, 1981, 20, 2429.

K. Kawazu, S . Nakajima, and M. Ariwa, Experientia, 1979, 35, 1294.
Sesquiterpenoids
177
---OR
co-occurs
with
(761) R
(762) R
(763) R
= AC
= Tig
= COC(Me)=CH,
'0
(764)
(769) R' = H, OH; R2 = 0

(770) R' = 0; R2 = H, OH
(771) R1= H, OAC; R2= H, OH
(772)
(773)
Some interesting new approaches to the synthesis of the hydroazulene skeleton

found in guaiane and pseudoguaiane sesquiterpenoids have been reported. These
include the synthesis of (774)353and the fluoride-induced fragmentation of the
two silyl ethers (775) and (776) to give (777).354A carefully thought out potential
synthesis of (778) by fragmentation and rearrangement of the alkoxide (779)
unfortunately went awry because the A7ps-enolateof (778) formed in the reaction
underwent a further intramolecular Michael reaction to produce (780).355Independent generation of this enolate also gave (780). Another product of the fragmentation reaction was the bicyclic ketone (781) whose structure could also be rationalized mechanistically from (779). Another interesting result was obtained from
363
s54
3bb
J. J. Christie, T. E. Varkey, and J. A. Whittle, J . Org. Chem., 1981, 46, 3590.

L.-F. Tietze and U. Reichert, Angew. Chem., Int. Ed. Engl., 1980, 19, 830.
C. M. Tice and C. H. Heathcock, J. Org. Chem., 1981, 46, 9.
178

OMS
o+
H OSiMe,
(774)
(775 )
(776)
0
(777)
&0-
(778)
(779)
the thermolysis of compounds such as (782) which gave predominantly (783) and
(784)356 before hydrolysis. A mechanistic rationale for the formation of these
compounds which includes a trimethylsilyl from one oxygen to another has been
given. A careful analysis of the thermally-induced tandem Cope-Claisen rearrangement of the vinyl ether (785) has shown that products (786) and (787) are formed
in the ratio of 7:3."' The mechanistic implications of this are that the initial Cope
rearrangement proceeds through a chairlike transition state preferentially, followed
by a Claisen rearrangement of the intermediate (788). The synthetic interest in (786)
and (787) is that they have been converted into a mixture of (789) and (790).
356
357
F. Audenaert and M. Vandewalle, Tetrahedron Lett., 1981, 22, 4521.

F. E. Ziegler and J. J. Piwinski, J. Am. Chem. SOC.,1980, 102, 6576.
Sesquiterpenoids
179
i
d
ii, iii
+
'1
Y-i
CHO
0
*.
I
0 -
HO
vii, viii
0
Jix-xii
kii-xv
v, vi
c-
HO
OH
\-xviii
(793)
(792)
Reagents: i, CuI.(MeO),P-CH,=CHCH,Br; ii, 0,-Me,S; iii, H 3 0 + ; iv, OH-; v, P,05MeS0,H; vi, LiAlH,; vii, Me,NCMe(OMe),-K,C03; viii, I,; ix, Bun3 SnH; x, (Me,N),
CHOMe; xi, Bu',AIH; xii, PCC; xiii, LDA; xiv, PhSeC1; xv, [ O ] ;xvi, DBN; xvii, H,-Pt02;
xviii, Ac,O-py
Scheme 68
In the area of total synthesis, a full description of aromaticin (791) has app e a ~ e d in
, ~addition
~~
to newly announced syntheses of aromatin (792) and confertin (793) (Scheme 68),359compressanolide (794) (Scheme 69),360and carpesiolin
(795) (Scheme 70).361
A full report on the short stereocontrolled synthesis of racemic patchouli alcohol
has been
the key steps of which are the Grignard addition of the
magnesium derivative of the bromide (796) to the dienone (797) followed by an
intramolecular Diels-Alder reaction. The preparation of the two enantiomers of
368
359
360
3s1
382
P. T. Lansbury and D . G. Hangauer, Jr., Tetrahedron, 1981, 37, Suppl. No. 1, 371.
F. E. Ziegler and J.-M. Fang, J. Org. Chem., 1981, 46, 825.
A. A. Devreese, P. J . De Clercq, and M. Vandewalle, Tetrahedron Lett., 1980, 21, 4767.
K. Nagao, M. Chiba, I. Yoshimura, and S.-W. Kim, Chem. Pharm. Bull., 1981, 29,2733.
F. Naf, R. Decorzant, W. Giersch, and G. Ohloff, Helv. Chim. Acta, 1981, 64, 1387.
180
P3 &
iii-v
+
i, ii
+
60
viii-x
iii, xi, viii
f---
t---
....
0
(794)
Reagents: i, (CH,OH),-PTSA; ii, cumylhydroperoxide-triton B; iii, LDA; iv, Me&=

CHCH,Br; v, Li-NH,; vi, 0,-Me,S; vii, Cr0,-H+; viii, H,O+; ix, CH,=PPh,; X, Me,SiClEt,N-DMAP; xi, Me1
Scheme 69
i-iv
ButO
o +v-viii
ButO
---OH
ButO
Jix, x
pii,
xix
(795)
Reagents: i, H2-Pt02; ii, MeO-; iii, LDA-CH,Br,; iv, BuLi; v, LDA; vi, PhSeBr; vii, HzOz;
viii, LiAlH,; ix, MCPBA; x, LiCH, CO,Li: xi, (CF,CO),O-py; xii, PTSA; xiii, DHP-H+;
xiv, aq. K,CO,; xv, CH,O; xvi, MsC1-py; xvii, DBU; xviii, PCC; xix, H,O+
Scheme 70
Sesquiterpenoids
181
(796) from (-)- and (+)-a-pinene has permitted syntheses of both natural (-)patchouli alcohol (798) and its antipode. The olfactory properties of these two
enantiomers are quite different, the natural isomer having the highly prized
earthy camphoraceous aroma while the unnatural ( +)-enantiomer is rather
nondescript and by no means reminiscent of patchouli oil, thus providing another
example of odour differences between enantiomers. This detailed study should settle
the long-standing claim that pure (-)-patchouli alcohol is odourless and that
norpatchoulenol (799) is responsible for the typical note of the essential oil.
It has now been shown that a very minor constituent of patchouli leaves is the diol
(800), previously obtained from mammalian hydroxylation of patchouli alcohol.3s3
This diol may be the precursor of the norsesquiterpene (799) in the plant. Patchouli
alcohol has been used as a test substance for a 13C n.m.r. technique which determines carbon connectivity by measurement and analysis of all one-bond 13C-13C
coupling constants at natural abundance
A limiting factor of this interesting
technique for natural product structural elucidation is the relatively large sample
required-3g of (798) in 0.3ml of C6D6.
An earlier synthesis of seychellene (801) has been reported in full and improvements in some-key steps have been accomplished.365(Vol. 9, p. 155, Vol 11, p. 84).
(799)
17 Aromadendrane, Nardosinane, Neolemnane, Bicyclogermacrane
In addition to the two sinularane derivatives isolated from the marine source
CZavularia injluta (see p. 114), the aromadendrane derivative (802) has also been
identified in the related species Clavularia k0e1likeri.l~Another aromadendrane
compound is the diol(803) obtained from the plant Senecio nemoren~is.~~
An X-ray
analysis of nardosinone has confirmed its structure as (804).366The soft coral
Lemnalia africana is a rich source of sesquiterpenoids and recent investigations
SO4
so5
866
E. Trifdieff, Phytochemistry, 1980, 19, 2467.

A. Neszmelyi and G. Lukacs, J. Chem. Sac., Chern. Cornmun., 1981, 999.
M.E. Jung, C. A. McCombs, Y.Takeda, and Y.-G. Pan, J. Am. Chern. SOC.,1981,103,6677.
J. Friemann, G. Rucker, T. Frohlich, A. Kirfel, and G. Will, Liebigs Ann. Chem., 1981, 2057.
7
182
H o W ' * * ( ) A c
How.'.b
H o W * , . IIo C ~
4OH
H+CHO
(805)
A
0
(807)
(806)
have uncovered some more examples. These include the ent-nardosinane-type
compounds (805)-(807).367 The metabolites from another sample of L. africana
collected from the Western Caroline Islands have been identified as (808)-(810),
(808) R
(809) R
=H
= AC
d
A
(819)
367
B. F. Bowden, J. C. Coll, S. J. Mitchell, B. W. Skelton, and A. H. White, Aust. J. Chem., 1980,

33, 2737.
Sesquiterpenoids
183
the first two of which have the novel neolemnane skeleton.368(-)-Spathulenol(8 1 1)

and its C-4 epimer have been synthesized from (-)-p-pinene by an adaptation of the
original Biichi synthesis of a r ~ r n a d e n d r e n e . ~ ~ ~
As noted in various places in this chapter, the identification of liverwort constituents has proved to be a very fruitful area of sesquiterpenoid chemistry. Several
papers have been published on this subject; see for example the systematic screening
of P l a g i o ~ h i l a ,F~r~~~l l a n i a ,R~ i~c~~ a r d i a ,P~a~l l~a ~ i c i n i a ,and
~ ~ ~ Conocephalum
species.373A full paper has been published on the great variety of ent-2,3-secoalloaromadendranes and related sesquiterpenoids isolated from Plagiochila
s e m i d e c ~ r r e n sMany
. ~ ~ ~ of these compounds have plant growth-inhibitory properties. The latest additions to this group of sesquiterpenoids are (+)-9a-acetoxyovalifoliene (8 1 2)375and tridensenone (8 1 3).46 Some interesting, biologically active
metabolites from the liverwort Lepidozia vitrea include (+)-vitrenal
(
8 14)376and
( -)-lepidozenal (8 1 5),37 the latter compound having the rare trans-fusion of the
cyclopropane ring. Previously ( -)-isobicyclogermacrenal (8 16) had been isolated
from this liverwort and there is a possible biogenetic link between it and ( +)-vitrenal
via ring contraction of the ent-allo-aromadendryl cation (817) derived from cyclization of (816).
A full paper on the photochemical synthesis of (818), a compound related to
taylorione (819), has been
18 Pinguisane
Some new pinguisane sesquiterpenoids have been isolated from liverwort species.
These include dehydropinguisanin (820),dehydropinguisenol(821), and pinguisenal
@
0
36 8
88 9
870
371
0 0
R. R. Izac, W. Fenical, B. Tagle, and J. Clardy, Tetrahedron, 1981, 37, 2569.

H. Surburg and A. Mondon, Chem. Ber., 1981, 114, 118.
Y. Asakawa, H. Inoue, M. Toyota, and T. Takemoto, Phytochemistry, 1980, 19,2623.
Y . Asakawa, R. Matsuda, M . Toyota, S. Hattori, and G. Ourisson, Phytochemistry. 1981, 20,
2187.
3 7a
878
374
875
3 76
377
378
Y. Asakawa, M. Toyota, R. Takeda, C. Suire, and T. Takemoto, Phytochemistry, 1981, 20,

725.
Y. Asakawa, R. Matsuda, and R. Takeda, Phytochemistry, 1981, 20, 1423.
A. Matsuo, K. Atsumi, M. Nakayama, and S. Hayashi, J . Chem. SOC.,Perkin Trans. 1, 1981,
2816.
A. Matsuo, K . Atsumi, K. Nadaya, M. Nakayama, and S. Hayashi, Phytochemistry, 1981,20,
1065.
A. Matsuo, S. Uto, H. Nozaki, M. Nakayama, and S. Hayashi, J . Chem. SOC.,Chem. Commun.
1980, 1220.
A. Matsuo, N. Kubota, M. Nakayama, and S. Hayashi, Chem. Lett., 1981, 1097.
G . Pattenden and D. Whybrow, J . Chem. SOC.,Perkin Trans. 1 , 1981, 1046.
184
(822) from Trocholejeunea s a n d v i ~ e n s i s .The

~ ~ ~last compound, together with
pinguisanin (823) and pinguisanolide (824) has been identified in Ptilidium pulcherr i r n ~ r nA
. ~new
~ ~ type of pinguisane, ptychanolide (825), has been obtained from
the liverwort Ptychanthus s t r i a t ~ sThe
. ~ ~spiro-lactone
~
function in this compound
is reminiscent of some of the fukinane sesquiterpenoids.
In a synthetic study of the pinguisane compounds, Jommi et al. have converted
the diene-dione (826) into 7-epipinguisone (827)382and pinguisone (828)383(Scheme
71).
i, iv
t--
a5
(828)
Reagents: i, Me,CuLi; ii, Br,-AcOH; iii, CaCO,; iv, CICH,COCI; v, 9-BBN; vi, Pr'SH;
vii, NaIO,; viii, A-CaCO,
Scheme 71
19 Miscellaneous
The two epimeric sesquiterpenoids (829) have been synthesized and shown to be
identical to minor constituents of Eumorphia p r ~ s t a t a Cantharidin
.~~~
(832) has,
378
a80
381
382
383
a64
Y. Asakawa, M. Toyota, M. Kano, and T. Takernoto, Phytochemistry, 1980, 19, 2651.

Y. Asakawa, R. Matsuda, and C. Suire, Phytochemistry, 1981, 20, 1427.
R. Takeda, H. Naoki, T. Iwashita, and Y. Hirose, Tetrahedron Lett., 1981, 22, 5307.
S. Bernasconi, M. Ferrari, P. Gariboldi, G. Jomrni, M. Sisti, and R. Destro, J. Chem. SOC.,
Perkin Trans. 1, 1981, 1994.
S. Bernasconi, P. Gariboldi, G. Jommi, S. Montanari, and M. Sisti, J. Chem. Soc., Perkin
Trans. 1, 1981, 2394.
F. Bohlmann and L. Fiedler, Chem. Ber., 1981, 114, 227.
Sesquiterpenoids
185
at long last, succumbed to a straightforward synthesis by way of a high-pressure

Diels-Alder reaction. 385 Thus, reaction of furan with the anhydride (830) in
dichloromethane solution at 15 kbars gives predominantly the adduct (83 1).
Treatment of this compound with Raney nickel produces cantharidin (832).
385
W. G . Dauben, C. R. Kessel, and K. H. Takemura, J. Am. Chem. SOC.,1980,102,6893.
3
Diterpenoids
BY J. R. HANSON
1 Introduction
This review follows the pattern of previous Reports with sections based on the
major skeletal types of diterpenoid. The literature that has been covered is that
which was available to August, 1981. The useful Kyoto series of reviews has
continued to appear.l An interesting number of new clerodanes have been obtained
from the Labiateae, particularly Teucrium species, and the absolute stereochemistries
of many of these have now been clarified. The extensive survey of the Compositae
by Bohlmann has led to the description of many new diterpenoids although some
of the structures which have been assigned purely on n.m.r. evidence require
confirmation by chemical inter-relationships. The occurrence of particular diterpenoid skeleta may have taxonomic significance. The chemistry of the gibberellin
plant hormones has attracted considerable attention during the year with a number
of total and partial syntheses being recorded. Marine organisms have continued
to yield many diverse types of diterpenoid skeleta.
2 Acyclic and Related Diterpenoids
20-Hydroxygeranylnerol has been obtained2 from Kingianthus paradoxus (Compositae). The biogenetic significance of a number of hydroxylated acyclic diterpenoids with internal cis double bonds [e.g. (l)], which were obtained from the
resin of Eremophila exilijiolia and E. glutinosa, has been discussedSin relation to
the cembrane and serrulatane diterpenoids which have been found in other
Eremophila species. Marine organisms have been the source of a number of alicyclic
diterpenoids. Some further acyclic diterpenoids [e.g. (2)] which are related to
crinitol and eleganolone have been obtained4 from the brown alga, Cystoseira
H OH
E. Fujita, K. Fuji, Y.Nagao, and M. Ochiai, Bull. Znst. Chern. Res., Kyoto Univ., 1980,58,484.
F. Bohlmann, J. Ziesche, H. Robinson, and R. M. King, Phytochemistry, 1981, 20, 1146.
E. Ghisalberti, P. R. Jefferies, and G. M. Proudfoot, Aust. J . Chem., 1981,34, 1491.
V. Amico, G. Oriente, M. Piatelli, G. Ruberto, and C. Tringali,Phytochemistry, 1981,20, 1085.
186
Diterpenoids
187
crinitu. The lactone (3), which may be derived by the internal hydrolysis of an
epoxide, was amongst the terpenoids which were obtained from A canthospermurn
uustrule.=
OH
(3)
3 Bicyclic Diterpenoids
Labdanes.-The 13C n.m.r. data for some labdanes related to andrographolide
have been reported6and 13Cn.m.r. methods have been applied to the determination
of the C-14 configuration of some 8,13-epoxylabdan-14-ols.The empirical correlation between structure and the optical rotation of the Cistus lubduniferus
diterpenoids has been questioned.6 A number of labdane 13-0-glycosides have
been obtained9 from Aster sputhulifolius (Compositae) and ent-3cr-hydroxy-13epimanool (4) has been obtained from Croton sublyrutus.1 Some labdane dialdehydes [e.g. ( 5 ) ] have been reportedll in Alpiniu species. In the course of a search
CH,OH
Br-
for compounds with insect anti-feeding activity, the grindelane diterpenoid (6)
and its succinate ester were isolated12from Crysothumnus nuuseosus (Compositae)
(rabbitbrush). Various diacetates of the grindelane diterpenoid lagochilin have been
F. Bohlmann,J. Jakupovic, A. K. Dhar, R. M. King, and H. Robinson, Phytochemistry, 1981,
20, 1081.
A. Patra, A. K. Mitra, S. Biswas, C. D. Gupta; A. Basak, and A. K. Barua, Org. Mugn.

Reson., 1981, 16, 75.
M. C. Garcia-Alvarez and B. Rodriguez, J. Org. Chem., 1981, 46, 1915.
* V. A. Paldugin, Khim. Prir. Soedin., 1981, 169.
* Y.Uchio, M. Nagasaki, S. E. Guchi, A. Matsuo, M. Nakayama, and S. Hayashi, Tetrahedron
Lett., 1980,21, 3775.
lo E. Kitazawa and A. Ogiso, Phytochemistry, 1981, 20, 287.
l1 H. Itokawa, M. Morita, and S. Mihaashi, Chem. Pharm. Bull., 1980, 23, 3452.
A. F. Rose, Phytochemistry, 1980, 19, 2689.
188
described.13 Some simple labdane acids are amongst14 the constituents of Morithamnus crassus and a number of labdanes and kolavenes were obtained15 from
Acritopappus (Compositae) species. Chemical and spectroscopic data have been
reported16for the structure of isoconcinndiol(7) which is a brominated diterpenoid
from the red alga Laurencia snyderae.
A series of andalusol derivatives (8) have been obtained1' from Sideritis foetens
(Labiatae). 7a-Acetoxytranscommunic acid (9) was reportedla from Chrornoluenu
collina. The acetate (10) and hemi-acetal (1 1) were describedlg as constituents of
(8) R' = H, R2 = OH, R3 = OAC

R1 = H, R2 = OAC,R2 = OH
R1 = OH, R2= H, R2 = OAC
(9)
(13)
Schkuhria species. Some labdane derivatives [e.g. (12)] were obtained20 from
Ageratium fastigiaturn. 7a-Hydroxylambertianic acid was isolated21from Gutierreziu
dracunculoides. Dodonaea species have been a rich source of bicarbocyclic diterpenoids. The X-ray crystal structure of the acid (1 3), obtained from D . petioluris,
has been reported.22
A further group of acetals has been prepared from m a n 0 0 1 ~for
~ structure-odour
studies. Some lY5-diepoxidesin this group underwent rearrangement based on the
intramolecular opening of 8@,9p-epo~ides.~~
(1 1)
(12)
R. Isiamov, U. N. Zainutdinov, and K. A. Aslanov, Khim..Prir. Soedin., 1981. 57.

F. Bohlmann, J. Jakupovic, H. Robinson, and R. M. King., Phytochemistry, 1980, 19, 2769.
I6 F. Bohlmann, C. Zdero, R. K. Gupta, R. M. King, and H. Robinson, Phytochemistry, 1980,
19, 2695.
I@ B. M. Howard and W. Fenical, Phytochemistry, 1980, 19, 2774.
M. C. Garcia-Alvarez and B. Rodriguez, Phytochemistry, 1980, 19, 2405.
Is F. Bohlmann, C. Zdero, L. Fiedler, H. Robinson, and R. M. King, Phytochemistry, 1981, 20,
la
I4
1141.
2o
21
a2
*a
24
F. Bohlmann, J. Jakupovic, H. Robinson, and R. M. King, Phytochemistry, 1980, 19, 881.

F. Bohlmann, M. Grenz, A. K. Dhar, and M. Goodman, Phytochemistry, 1981,20, 105.
F. Bohlmann, M. Ahmed, R. M. King, and H. Robinson, Phytochemistry, 1981, 20, 1434.
P. R. Jefferies, T. G. Payne, C. L. Raston, and A, H. White, Aust. J. Chem., 1981, 34, 1001.
P. K. Grant and D. D. Rowan, Aust. J . Chem., 1981, 34, 1959.
P. K. Grant and D. D. Rowan, Aust. J. Chem., 1981,34, 1975.
D iterpenoids
189
C1erodanes.-A number of bicyclic diterpenoids such as the labdane-lactone (14)

and the epoxy-kolavane(1 5 ) are amongst the constituents of Hartwrightia J I ~ r i d a n a ~ ~
and some further clerodanes related to bacchotricuneatin B were obtainedz6from
Baccharis species. Some kolavanes were reportedz7 as constituents of Liatris
scariosa. A chemical correlation has been established2* between the cis- and
trans-clerodane diterpenoids. A revision of the structures assigned to several
solidagolactones (elongatolides) has been proposed.29A tricarbocyclic lactone (16),
w
**.
which may be formed by the base-catalysed cyclization of a cis-clerodane, has been

isolated30 from Solidago altissima. Its structure was established on the basis of its
spectral data and an X-ray analysis of the corresponding triol. The X-ray structure
of the diacetate of a transclerodane (17) isolated from Pityrodia Iepidota (Verbenaceae) has been reported.31 The structure (18) has been assigned32on the basis
of n.m.r. evidence to a clerodane lactone from Bahianthus viscidus. A full paper
has appeared33on the identification of the 5,lO-seco-clerodanesof Conyza stricta.
Croton (Euphorbiaceae) species have afforded several types of diterpenoid.
Penduliflaworosin (1 9), isolated34 from C. pendulzJ7orus, represents a structure
a5
J. Jakupovic, A. K. Dhar, F. Bohlmann, R. M. King, and H. Robinson, Phytochemistry, 1981,

20, 843.
F. Bohlmann, C. Zdero, M. Grenz, A. K. Dhar, H. Robinson, and R. M. King,Phytochemistry,
e7
F. Bohlmann, M. Ahmed, H. Robinson, and R. M. King, Phytachemistry, 1981, 20, 1439.

I. Kitagawa, T. Kamigauchi, K. Yonetani, and M. Yoshihara, Chem. Pharm. Bull., 1980,28,
24-03.
M. Niwa and S. Yamamura, Tetrahedron Lett., 1981, 22, 2789.
S. Yamamura, M. Ito, M. Niwa, I. Hasegawa, S. Ohbao, and Y. Saito, Tetrahedron Lett.,
1981, 22, 739.
E. Ghisalberti, P. R. Jefferies, C. L. Raston, R. F. Toia, and A. H. White, Aust. J. Chem.,
1981, 20, 281.
ao
a1
1981, 34, 1009.

a2
a4
F. Bohlmann, R. K. Gupta, R. M. King, and H. Robinson, Phytochemistry, 1981, 20, 331.

S. B. Mahato, A. K. Sen, P. C. Mazumdar, and K. Yamasaki, Phytochemistry, 1981, 20, 850.
K. A. Adesogan, J. Chem. Sac., Perkin Trans. I , 1981, 1151.
190
intermediate between the labdane and clerodane series. A similar feature is revealed35
by the 19-epimeric hemi-acetals, mallotucins C and D (20), which are constituents
of Mallotus repandus (Euphorbiaceae). Sonderianin (21) is a clerodane which was
from Croton sonderianus, and the diacetate (22) has been reported37 as
a constituent of C . pyramidalis. The structure (23) of croverin, which was obtained
from C . verreauxii, was determined3* by X-ray analysis.
Although the absolute configuration of these clerodanes from Croton species

was not determined, the absolute stereochemistry of a number of clerodanes from
Teucrium (Labiatae) species has been clarified.39 19-Acetylgnaphalin and isofruticolone were shown to belong to the neoclerodane series. Teuflin (24) has been
obtained40 from Teucrium viscidum and details of an X-ray structure have been
published.41The structure (25), without absolute configuration, was assigned42to
35
86
T. Nakatsu, S. Ito, and T. Kawashima, Heterocycles, 1981, 15, 241.

A. A, Craveiro, E. R. Silveira, R. F. Braz, and I. P. Mascarenhas, Phytochemistry, 1981, 20,
852.
s7
38
ag
40
48
L. Rodriguez-Hahn, A. Valencia, R. Saucedo, E. Diaz, and G . Negron, Rev. Latinoam. Quim.,

1981, 12, 16 (Chem. Abstr., 1981, 94, 205 402).
E. Fujita, M. Node, K. Nishida, M. Sai, K. Fuji, A. T. McPhail, and J. A. Lamberton, J . Chem.
Sac., Chem. Commun., 1980, 920.
M. Martinez-Ripoll, J. Fayos, B. Rodriguez, M. C . Garcia-Alvarez, G. Savona, F. Piozzi,
M. Paternostro, and J. R. Hanson, J. Chem. SOC.,Perkin Trans. I , 1981, 1186; for a review see
F. Piozzi, Heterocycles, 1981, 15, 1489.
M. Node, M. Sai, and E. Fujita, Phytochemistry, 1981, 20, 757.
M. Node, M. Sai, E. Fujita, and A. T. McPhail, J. Chem. Res. (S), 1981, 32.
G. Papanov, P. Malakov, and F. Bohlmann, Phytochemistry, 1981, 20, 170.
Diterpenoids
191
J
\
O0
OAc
(27)
(28)
(29)
teuscordinon from T. scordium. The structures of capitatin (26)43and lolin (27)44'

obtained from T. capitatum were determined by X-ray analysis. Teucapitatin (28),
obtained from the same source, was related to picropolin. The structure of auropolin
(29), from T.polium subsp. aureum, was deduced45from an X-ray analysis of the
OAc
43
44
46
OAc
C. Marquez, R. M. Rabanal, S. Valverde, L. Eguren, A. Perales, and J. Fayos, Tetrahedron

Lett., 1980, 21, 5039.
C. Marquez, R. M. Rabanal, S. Valverde, L. Eguren, A. Peralse, and J. Fayos, Tetrahedron
Lett., 1981, 22, 2823.
L. Eguren, A. Peralse, J. Fayos, G. Savona, M. Paternostro, F. Piozzi, and B. Rodriguez,
J. Org. Chem., 1981,46, 3364.
192
corresponding lactone. The clerodanes obtained from Ajuga (Labiatae) species

have attracted attention because of their insect anti-feedant activity. The structures
of some further clerodanes, ajugareptansone A (30) (ajugareptansone B is the
A2-elimination
from A . reptans and ajugamarin (31)47 from A . nipponensis, were established by X-ray analysis.
4 Tricyclic Diterpenoids
Naturally Occurring Substances.-The I3C n.m.r. data for isopimara 15,16-diols

and the corresponding sandaracopimara- 15,16-diols have been correlated48 with
their structures and the 13C n.m.r. spectra of some ent-rosane diterpenoids have
been assigned.49 19-Norisopirnara-7,15-dien-3-one
has been isolated50 from the
fungus Acrernoniurn luzulae. The pimarane diterpenoid (32) has been isolated5
from a Vellozia species and the trio1 (33) has been reported52 as a constituent of
SMe
(35)
(36)
(37)
Prernna latifolia. The structure of the unusual ether (34), obtained from Acacia
Zeucophloea,was established by X-ray analysis.53Micrandrol C (35) and micrandrol
D (36) are constituents of Micrandropsis ~ c l e r o x y l o nUrbalactone
.~~
(37) is another
49
F. Camps, J. C. Coll, and A. Cortel, Chem. Lett., 1981, 1093.
48
E. Wenkert, T. D. J. Halls, P. Ceccherelli, M. Curini, and R. Pellicciari, J . Org. Chem., 1981,
(H. Shimomura, Y. Sashida, K. Ogawa, and Y. Litaka, Tetrahedron Lett., 1981, 22, 1367.
O8
Lo
6a
63
64
46, 3135.
M. C. Garcia-Alvarez, B. Rodriguez, S. Valverde, B. M. Fraga, and A. G. Gonzalez, Phytochemistry, 1981, 20, 167.
N. Cagnoli, P. Ceccherelli, M. Curini, N. Spagnoli, and M. Ribaldi, J . Chem. Res. (S), 1980,
276.
A. C. Pinto, L. M. Valente, R. S. Da Silva, W. S . Garzez, and P. P. Queirez, An. Acad. Bras.
Cienc., 1981, 53, 73 (Chem. Abstr., 1981, 95, 98 071).
B. C. Rao, K. Suseela, and E. K. S. Vijayakumar, Indian. J. Chem., Sect. B, 1981, 20, 175.
A. Perales, M. Martinez-Ripoll, J. Fayos, R. K. Bansal, K. C. Joshi, R. Patni, and B. Rodriguez, Tetrahedron Lett., 1980, 21, 2843.
M. A. De Alvarenga, J. J. Da Silva, H. E. Gottlieb, and 0. R. Gottlieb, Phytochemistry, 1981,
20, 1159.
193
Diterpenoids
member of the podolactone series which have been isolated from Podocarpus
~ r b a n i iA
. ~ ~further report has appeared56 on the caesalpin from Caesalpinia
bonducella.
Diterpenoid quinones have been isolated from a number of the Labiatae. An
o-quinone, ethiopinone (38), has been described as a c o n ~ t i t u e nof
t ~ the
~ roots of
Salvia aethiopis (Labiatae) and the known quinones horminone and 7cc-acetoxyroyleanone have been isolated58from S. lanata. The dehydroabietic acid derivative
(39) was obtained59from S. tomentosa. The partial synthesis of the epimeric ring B
C0,Me
(39)
(40)
(41)
mono- and di-hydroxyroyleanones has been reported60 and coleon U has been
synthesized61from a podocarpic acid derivative.
Some unusual rearranged tricyclic diterpenoids with a cis- A/B ring fusion have
been isolated62 from Rondeletia panamensis (Rubiaceae). Panamensin has the
structure (40) whereas its dihydro-derivative, rondeletin, has the 2-keto structure
(41).
Chemistry of the Tricyclic Diterpenoids.-The addition of chlorosulphonyl isocyanate to the methyl esters of levopimaric and neoabietic acids with the formation
of C-12 carboxyamides has been described.63 The well documented aromatic
substitution reactions of dehydroabietic acid continue to be examined,64together
65
5
.'
6B
Eo
Ea
63
6*
B. Dasgupta, B. A. Burke, and K. L. Stuart, Phytochemistry, 1981, 20, 153.

K. K. Purushothaman, K. Kalyani, K. Subramanian, and S . Shanmuganathan, Indian J.
Chem., Sect. B, 1981, 20, 625.
M. T. Boya and S. Valverde, Phytochemistry, 1981, 20, 1367.
K. S . Mukherjee, P. K. Ghosh, and S . Badruddoza, Phytochemistry, 1981, 20, 1441.
A. Ulubelen, M. Miski, and T. J. Mabry, J . Nat. Products, 1981, 44, 119.
H. Meier, P. Rueedi, and C. H. Eugster, Helv. Chim. Acta, 1981, 64, 630.
S. Savard, M. Neron Desbiens, and R. H. Burnell, Synth. Commun., 1981, 11, 399.
K. Koike, G. A. Cordell, N . R. Farnsworth, A. A. Freer, C. J. Gilmore, and G. A. Sim,
Tetrahedron, 1980, 36, 1167.
G. Mehta, D. N. Dhar, S. C. Suri, M. M. Bhadbhade, and K. Venkatesan, Indian J. Chem.,
Sect. B, 1981, 20, 193.
H. Akita and T. Oishi, Chem. Pharm. Bull., 1981, 29, 1567.
194
with the cleavage65of the aromatic ring to form drimane sesquiterpenoids. The
preparation of shonanol from dehydroabietic acid has also been reported.66 An
improved route for the synthesis of methyl vouacapenate from podocarpic acid
has been de~cribed.~'
The photo-oxygenation of pimara-8-enes and isopimara-8-enes to afford the
As(14)-9-alcohols has been described.6s The preparation and cleavage of some
isopimarane-7,8-epoxides,with the formation of
(11 )-dienes, has been examStudies on the rearrangement of some 8a,9a-epoxypodocarpanes with boron
trifluoride etherate have been directed 70 at inducing a backbone rearrangement to
afford the rimuene skeleton. The structure of an unusual pentacyclic ether (43),
prepared by the action of boron trifluoride etherate on the epoxypimarane (42),
A799
CH202CPh
(42)
(43)
(44)
(45)
was established'l by X-ray analysis. The acid (45)was formed72by carbonylation
of dihydroabietic acid (44)in the presence of carbon monoxide. The cyclization of
methyl copalate to the tricyclic analogue of isoagathic acid has been followed75
by the conversion of the product into the enantiomer of the marine diterpenoid
spongiadien- 12-01.
The stereochemistry of the S,i cyclization in the biosynthesis of ent-sandaraco~ i m a r a d i e n eand
~ ~ virescenol B 75 has been studied using stereospecifically
as
O6
67
H. Akita and T. Oishi, Chem. Pharm. Bull., 1981, 29, 1580.

T. Matsumoto, S. Irnai, H. Kawashima, and M. Mitsuki, Bull. Chem. SOC.Jpn., 1981,54,2099.
G. Jommi, S. Bernasconi, P. Gariboldi, M. Sisti, and P. Tavecchia, J. Org. Chem., 1981, 46,
3719.
69
'O
71
74
7s
P. Ceccherelli, M. Curini, and R. Pellicciari, J . Chem. Res. ( S ) , 1981, 77.

M. Curini, P. Ceccherelli, R. Pellicciari, and E. Sisani, Gazz. Chim. Ztaf., 1980, 110, 621.
T. Nakano, A. Haces, A. Martin, and A. Rojas, J. Chem. SOC.,Perkin Trans. I , 1981, 2075.
J. W. Blunt, E. J. Ditzel, M. P. Hartshorn, L. H. Sieng, M. H. G. Munro, and W. T. Robinson,
B. E. Cross and M. R. Firth, J. Chem. Res. (S), 1981, 216.
D. S. De Miranda, G. Brendolan, P. M. Imamura, M. Gonzalez Sierra, A. J. Marsaidi, and
E. A. Ruveda, J. Org. Chem., 1981,46,4851.
K. A. Drengler and R. M. Coates, J. Chem. SOC.,Chem. Commun., 1980, 856.
D. E. Cane, H. Hasler, J. Materna, N. Cagnoli-Bellavita, P. Ceccherelli, G. F. Madruua, and
J. Polonsky, J. Chem. SOC.,Chem. Commun., 1981, 280.
Diterpenoids
195
deuteriated substrates. The cyclization has been shown to proceed with the antistereochemistry .
5 Tetracyclic Diterpenoids
Kaurenoid Diterpenoids.-The 13C n.m.r. spectra of some 18-hydroxykaur-16-enes

have been assigned.76The application of these results to the determination of the
stereochemistry of substituents at C-4 has been discussed. Authentic phyllocladan16p-01 has been prepared77from phyllocladene. It differs from the phyllocladan16p-01 which was previously reported to occur naturally. The latter had very
similar physical constants to phyllocladanol (the 16a-epimer). ent-Kauran-l6a,
17-diol has been
from Aristolochia eleguns. Derivatives of ent-l5ahydroxykaurenoic acid are quite common. The cinnamic acid ester has been
isolated79from Wedeliu gluucu (Compositae) and some other esters have been
obtaineds0from Ichthyothere (Compositae) species. Crystallographic studies have
establisheds1 the structure (46) for pterokaurene L,, which was isolated from Pteris
longipes, and (47) for pteroatisene P,, which was isolated from P.purpureorachis.
:*
H
CO,H
(48)
CO,H
(49)
The synthesis of some 18-norkaurene-15-carboxylic

acids from 4p, 18-norkaurene3-one has been describeds2 as has the synthesis of 15-carbo~ykaurene.~~
The
preparation of a series of fluorinated kaurenoids, including 16,16-difluoro-17norkauran- 19-oic acid from xylopic acid, has been described. 84 Ruboside, from
7~
A. G . Gonzalez, B. M. Fraga, M. G . Hernandez, and J. R. Hanson, Phytochemistry. 1981,20,

846.
R. M. Carman, Aust. J . Chem., 1981, 34,923.
83
M. A. A. Habib and N. A. El-Sebakhy, Pharmazie, 1981,36,291.

J. C. Oberti, A. B. Pomilio, and E. G . Gros, Phytochemistry, 1980, 19, 2051.
F. Bohlmann, C. Zdeto, H. Robinson, and R. M. King, Phytochemistry, 1981,20, 522.
T. Murakami, N. Tanaka, H. Iida, and Y . Iitaka, Chem. Pharm. Bull., 1981, 29, 773.
A. L. Cossey, L. N. Mander, and J. V. Turner, Aust. J. Chem., 1980, 33, 2061.
D. P. Popa, G . S. Pasechnik, A. M. Reinbold, and M. V. Atimoshone, Khim. Prir. Soedin.,
84
B. E. Cross, A. Erasmuson, and P. Filippone, J . Chem. SOC.,Perkin Trans. I , 1981, 1293.
78
79
82
1981,217.
196
Rubus chingii (Rosaceae), is a close relative of stevioside and is the p-D-glucosyl

ester of 13-O-~-~-glucosylstevio1.~~
Some 12-oxygenated ent-Ag(11)J6-kauradienes
have been obtaineds6from Vellozia caput-ardeae and the ,Ag(11)-dehydro-derivatives
of trachylobanic and stachenic acids were isolateds7 from Viguiera species. The
unusual 9(10)-secokaurene structure (48) has been proposedss for a lactone
obtained from Gnaphalium undulatum (Compositae). Some tumour-inhibitory
phyllocladene-based diterpenoids including (49) have been obtainedsg from
Bromel ia pinguin .
Although a number of Isodon species have been reclassified as Rabdosia
(Labiatae) species, their similarity is revealed by the highly hydroxylated kaurenoids
which they contain. Effusin, which was isolated from R. eflusus and shown to
inhibit insect growth, possessesg0the unusual spiro-secokaurene structure (50). A
(50) R
(51) R
=
=
H
OH
&
'3.H
HO
R2H2C OH
(54)
(55)
(56)
(57)
R' = H, R2 = OAC
R' = OH, R2 = OAC
R1= OACR2 = H
R' = OAC,R2 = OAC
similar structure (5 1) for trichorabdal B, another diterpenoid from the same plant,
was establishedg1 by X-ray analysis. On treatment with sodium hydroxide this
compound underwent a retro-Claisen and aldol condensation to afford (52).
Excisanin A (53) and B (the 12-acetate) are hydroxylated kaurenoids which were
T. Tanaka, H. Kohda, 0.Tanaka, F. H. Chen, W. H. Chou, and J. L. Leu, Agric. Biol. Chem.,
1981,45,2165.
A. C. Pinto, S. K. Do Prado, and R. Pinchin, Phytochernistry, 1981, 20, 520.

F. Bohlmann, J. Jakupovic, M. Ahmed, M . Grenz, H. Suding, H. Robinson, and R. M. King,
Phytochemistry, 1981, 20, 113.

R. Raffauf, M. D. Menarchy, P. W. LeQuesne, E. V. Arnold, and J. Clardy, J. Org. Chem.,
1981,46, 1094.
O0
I. Kubo. T. Kamikawa, T. Isobe, and T. Kubota, J . Chem. SOC.,Chem. Commun., 1980, 1206
E. Fujita, K . Fuji, M. Sai, M . Node, W. H. Watson, and V. Zabel, J . Chem. Soc., Chem,
Commun., 1981,899.
Diterpenoids
197
obtainedg2from R . excisa, and the longikaurins C, D, E, and F (54)-(57)

are a
group of antibacterial diterpenoids from R . Zongituba.93
The structures of the leukamenins I-VI (58)-(63), which were isolated from
R. umbrosia, were establishedg4by spectral studies and a series of chemical correlations. The glycosides shikokiasides A (64) and B (65), from R. shikokiana,
have a similar oxygenation pattern. 95
R 3
= R3 = R4 = OH, R2 = OAC
(59) R' = R2 = OAC,R3 = R4 = OH
(60)R' = R2 = R4= OAC,R3 = OH
(61) R' = R2 = R3 = OAC,R4 = OH
(62) R1 = H, R2 = OAC, R3 = R4 = OH
(58) R'
(64) R
(65) R
= OH
=H
Gibberellins.-Considerable effort has been directed at the study of the gibberellin

plant hormones. A useful procedure for the g.c.-m.s. identification of permethylated gibberellins has been described.96 The separation of some gibberellins by
adsorption and reversed-phase partition h.p.1.c. has been reported. 97 Evidence
(66), and a range of
has been presentedg8 for the structure of gibberellin
gibberellins, including the 1-hydroxygibberellinsA,, and A,, which were previously
obtained from G .fujikuroi, have been obtained from developing wheat grain.gg
Several aspects of the chemistry of gibberellic acid have been studied. The
3-hydroxy-group has been shownlo0to participate in the rearrangement of Al (2)gibberellin 19-10-lactones to the isomeric Al (l0)-gibbere1lin19-2-lactone (67).
g9
H.-D. Sun, X.-C. Sun, Z.-W. Lin, Y.-L. Xu, Y. Minami, T. Marunaka, and T. Fujita, Chem.
Lett., 1981, 753.
T. Fujita, Y. Takeda, and T. Shingu, Heterocycles, 1981, 16, 227.
Y. Takeda, T. Fujita, and A. Ueno, Chem. Left., 1981, 1229.
T. Isobe, Y. Noda, K. Shibata, and T. Kubota, Chem. Lett., 1981, 1225.
L. Rivier, P. Gaskin, K. Y . S. Albone, and J. MacMillan, Phytochemistry, 1981, 20, 687.
J. T. Lin and E. Heftmann, J. Chromatogr., 1981, 213, 507.
T. Yokota and N. Takahashi, Agric. Biol. Chem., 1981, 45, 1251.
P. Gaskin, P. S. Kirkwood, J. R. Lenton, J. MacMillan, and M. E. Radley, Agric. Biof. Chem.,
loo
P. S. Kirkwood, J. MacMillan, and M. L. Sinnott, J . Chem. Soc., Perkin Trans. I , 1980, 2117.
O8
93
94
86
96
O7
88
1980,44, 1589.
198
(68) R = Hal
(69) R = H
Several groups have reported lo1-lo3the isomerization of h1( 2 )-3-hydroxygibberellins
to A2 ( 3 )- 1-chlorogibberellins (68) on treatment with various halogenating agents.
Hydrogenolysis of the 1-halides provides a convenient route for the preparation of
gibberellin A, (69). The hydrogenolysis of 13-chlorogibberellins by tributyltin
hydride has also been reported. The partial synthesis of gibberellins A7,104A,, and
A2t05from gibberellic acid has been described together with routes for the preparation of labelled gibberellins A29and A51.106
The unsaturated ketone (70) is a catabolite of gibberellin A29. It has been preparedlo7 from gibberellic acid. The 2-position of gibberellins is metabolically
reactive and consequently the biological activity of a number of 2-substituted
derivatives of gibberellin A, including the 2-methyl compounds have been examined.108~10g

The rates of glucosylation of the 3- and 13-hydroxy-groups have been
examinedllo in the light of the occurrence of a number of gibberellins as their
glucosides. The photodimerization of 3-dehydrogibberellins occurs across the
1,2-double bond. Since this can occur in the crystalline state, the crystal structure of
3-dehydrogibberellin A3 methyl ester has been determinedlll in this context. The
corresponding reactions of dimethyl 3-dehydrogibberellenate have also been
examined.l12 The transformation of some gibberellin A, derivatives with palladium
acetate catalysis has been r e p 0 r t ~ d .A
l ~full
~ paper has appeared on the preparation
of 7-deoxygibberellin
A number of improved procedures for the degradation
B. E.Cross and I. C. Simpson, J . Chem. SOC.,Perkin Trans. I , 1981, 98.
J. R. Bearder, P. S. Kirkwood, and J. MacMillan, J . Chem. SOC.,Perkin Trans. I , 1981, 672.
lo3 J. R.Hanson, British Plant Growth Regulator Group Monograph, 1980, 5, 5 .
lop M. H.Beale and J. MacMillan, J . Chem. Res. ( S ) , 1980, 289.
lo5 Z. J. Duri, B. M. Fraga, and J. R. Hanson, J. Chem. SOC.,Perkin Trans. I , 1981, 161.
lo* M. H. Beale and J. MacMillan, J . Chem. SOC.,
10' P. Gaskin, P. S . Kirkwood, and J. MacMillan, J . Chem. SOC.,Perkin Trans. I , 1981, 1083.
lo8 M. H. Beale and J. MacMillan, Phytochemistry, 1981, 20, 693.
log G. V. Hoad, B. 0. Phinney, V. M. Sponsel, and J. MacMillan, Phytochemistry, 1981, 20, 703.
11* G.Schneider, Tetrahedron, 1981, 37, 545.
L. Kutschabsky, G. Reck, E. Hoehne, B. Voigt, and G. Adam, Tetrahedron, 1980, 36, 3421.
H. K. Al-Ekabi, G. A. W. Derwish, G. Adam, and K. Schreiber, Tetrahedron, 1981, 37, 1735,
lol
Io2
1741.
113
114
E.P.Serebryakov, Izv. Akad. Nauk SSSR, Ser. Khim., 1980, 2596.

M.Lischewski and G. Adam, Tetrahedron, 1980, 36, 1237.
Diterpenoids
199
of gibberellin A, have been noted115and a method for introducing a 15-carboxygroup has been described.l16
Methanolysis of' a C-20' mixed anhydride of gibberellin A,, gave the unusual
19-ortho-ester, the structure (71) of which was established by X-ray a n a 1 ~ s i s .The
l~~
formation of this compound and the corresponding 19-epimeric 20-tl9-lactols by
sodium borohydride reduction of the mixed anhydrides reveals the facile participation of the 19-estersin the reactions of C-20. This feature may be of biosynthetic
significance.
A number of metabolic studies have been reported in connection with gibberellin
biosynthesis. ent-Kaur-6,16-dien-19-oic acid has been described as a key intermediate in the biosynthesis of the kaurenolides in Cucurbita maxima.l18 The
production of 16,16-difluoro- derivatives of gibberellin A, and 7-hydroxykaurenolide using 16,16-difluoro-17-norkauranoic acid as a substrate with G. fujikuroi
has been reported,l19 and ent-15p-fluorokaurenoic acid has been shown to give rise
to a group of 15-fluorinated gibberellins.lZ0Some 7-fluorogibberellins may act as
gibberellin biosynthesis inhibitors.lZ1The production of 12p-hydroxygibberellins
by incubation of the corresponding ent- 12a-hydroxykaurene with Gibberella
fujikuroi has also been described.122
Graymotoxins.-The X-ray crystal structures for grayanotoxins XVI-XIX have
been r e p ~ r t e d . ~Routes
~ ~ - ~to~1,5-secograyanotoxins
~
(grayanol) derivatives have
been d e ~ c r i b e d . ~ ~ ~ ~ ~ ~ ~
Atiserenes.-The
1 1a,16,17-trihydroxyatiserene structure has been proposedlZ8
for atisideritol, obtained from Sideritis pusilla (Labiatae), on the basis of chemical
and spectroscopic evidence.
6 Macrocyclic Diterpenoids
Marine organisms, particularly corals, have continued to be a source of novel
diterpenoids. Cembrenene (72) and mayol (73) are two new cembranoid diterpenoids from the soft coral Sinularia mayi.129The cembrene alcohol (74) has been
116
L. Lombardo, L. N. Mander, and J. V. Turner, Aust. J. Chem., 1981,34, 745.
116
L.N . Mander, J. V. Turner, and B. Twitchin, Tetrahedron Lett., 1981, 22, 3017.
11'
118
119
B. M. Fraga, A. G. Gonzalez, M. G. Hernandez, F. G. Tellado, J. R. Hanson, and P. B.

Hitchcock, J. Chem. SOC.,Perkin Trans. I , 1981, 2740.
P.Hedden and J. E. Graebe, Phytochemistry, 1981,20, 1011.
B. E.Cross and P. Filippone, J . Chem. SOC.,Chem. Commun., 1980, 1097; J . Chem. Res. ( S ) ,
1981, 166.
B. E. Cross and A. Erasmuson, J . Chem. SOC.,Perkin Trans. I , 1981, 1918.

131 K.Boulton and B. E. Cross, J . Chem. SOC.,
1z2 K.Wada, T. Imai, H. Yamashita, Agric. Biol. Chem., 1981, 45, 1833.
A. Furusaki, S. Gasa, R. Ikeda, and T. Matsumoto, Bull. Chem. SOC.Jpn., 1981, 54,49.
A. Furusaki, S. Gasa, R. Ikeda, T. Matsumoto, N. Yasuoka, and Y. Matsuura, Bull. Chem.
SOC.Jpn., 1981, 54, 657.
135 A. Furasaki, S. Gasa, R. Ikeda, T. Matsumoto, N. Yasuoka, and Y. Matsuura, Bull. Chem.
SOC.Jpn., 1981, 54, 1622.
T. Terai, H. Meguri, N . Hamanaka, T. Matsuzaki, A. Furusaki, T. Kato, and T. Matsumoto,
Chem. Lett., 1980, 1111.
le7 T. Kaiya, N . Shirai, and J . Sakakibara, J . Chem. SOC.,Chem. Commun., 1981, 22.
lZ8 A. Garcia-Granados, A. Parra, A. Pena, A. Saenz de Buruaga, J. M. Saenz de Buruaga, and
S. Valverde, Tetrahedron Lett., 1980, 21, 361 1.
la* Y.Uchio, H. Nabeya, M. Nakayama, S. Hayashi, and T. Hasa, Tetrahedron Lett., 1981, 22,
Iso
1689.
200
(75)
(76)
obtained130from S.facile and cembrene C, sarcophytol B, flaccidoxide (75) were

isolated131from the Red Sea coral, Alcyoniumflaccidurn. The constituents of samples
of the coral Lobophytum crassum vary with the site of collection. Evidence has been
for the structure (76) for decaryiol, which was isolated along with
3,4-epoxynephthenol from Sarcophyton decanyi. A full paper giving X-ray crystallographic evidence has been presented133for the structure for emblide, a cembranolide from Sarcophyton glaucum, and a number of minor constituents of this coral
have also been r e p 0 ~ t e d . lThe
~ ~ stereochemistry of the 13-membered ring cembranolide diterpenoids from the coral Lobophytum pauciflorum has been elucidated.135 The X-ray crystal structure of the triepoxide of cembrene has been
reported,136revealing a remarkable stereoselectivity in its formation.
The Euphorbiaceae are the source of a number of diterpenoids derived by the
cyclization of macrocylic systems. Chemical, spectral, and X-ray crystallographic
evidence has been presentedl3' for the structure (77) for crotonitenone, a casbene
diterpenoid obtained from Crotoiz nitens. A group o f irritant esters with the
daphnane and tigliane skeleta have been reported13*from the roots of Stillingia
sylvatica. Linifolins A (78) and B (79) are piscicidal constituents of Pimilea species.139
Some aspects of the chemistry of ingenol have been reported.l*O
130
131
132
B. F. Bowden, J. C. Coll, S. J. Mitchell, and R. Kazlauskas, Aust. J . Chem., 1981, 34, 1551.
Y. Kashman, S. Carmely, and A. Groweiss, J . Org. Chem., 1981, 46,3592.
S . Carmely, A. Groweiss, and Y. Kashman, J . Org. Chem., 1981, 46, 4279.
J. A. Toth, B. J. Burreson, P. J. Scheur, J. Finer-Moore, and J . Clardy, Tetrahedron, 1980, 36,
1307.
134
136
13e
la'
I38
lP0
T. Nakagawa, M. Kobayashi, K. Hayashi, and H. Mitsuhashi, Chem. Pharm. Bull., 1981, 29,
Y . Yamada, S. Suzuki, K. Iguchi, I. Kikuchi, Y. Tsukitani, H. Horiai, and F. Shibayama,
Tetrahedron Lett., 1980, 21,3911.
V. A. Paldugin, N. I. Yaroshenko, and Y . V. Gatilov, Khim. Prir. Soedin., 1981, 174.
B. A. Burke, W. R. Chan, K. 0. Pascoe, J. F. Blount, and P. S. Manchand, J . Chem. SOC.,
Perkin Trans. 1, 1981, 2666.
W. Adolf and E. Hecker, Tetrahedron Left., 1980, 21,2887.
M. I. Tyler and M. E. H. Howden, Tetrahedron Lett., 1981, 22,689.
H. J. Opferkuch, W. Adolf, B. Sorg, S. Kusumoto, and E. Hecker, 2.Naturforsch., Teil B,
1981, 36, 878.
Diterpenoids
20 1
(78) R = OAC
(79) R = H
7 Miscellaneous Diterpenoids
Taonianone (80) is an unusual furan obtained141from Taonia australasica. A full
paper has appeared142on the structures of the diterpenoids based on the dolabellane
skeleton which were obtained from Dictyota dichotoma. 18-Hydroxydollabella3,7-diene (81) is another member of this group of compounds obtained from the
same source. A number of tricyclic relatives with the dolastane ring system,
including (82), were isolated144from Dictyota divaricata. Spectral and chemical
evidence has been
for the structure (83) of linearol, obtained from
a
HO
(84)
141
148
143
lP4
145
(85)
P.T. Murphy, G. March, and R. J. Wells, Tetrahedron Left.,1981, 22, 1555.

V. Amico, G. Oriente, M. Piattelli, C. Tringali, E. Fattorusso, S. Magno, and L. Mayol,
Tetrahedron, 1980,36, 1409.
V. Amico, R. Currenti, G. Oriente, M. Piattelli, and C. Tringali, Phytochemistry, 1981,20,848.
H. H. Sun,0.J. McConnell, W. Fenical, K. Hirotsu, and J. Clardy, Tetrahedron, 1981,37,1237.
M. Ochi, I. Miura, and T. Tokoroyama, J. Chem. SOC.,Chem. Commun., 1981, 100.
202
Dictyota linearis. This name has been used previously for another diterpenoid.
The unusual tricyclic structure (84) has been proposed for the spatane diterpenoids,
which were
from the alga Stoechospermum marginatum (Dictyotaceae).
A diterpenoid (85) related to cladiellin has been isolated147from a Pacific soft coral,
and a further member of the asbestinin series, asbestinin epoxide, was obtained14s
from the Caribbean gorgonian, Briareum asbestinum.
Full papers have appeared on the
and absolute configuration150 of
the decipiene diterpenoids. The structure (86) was assigned151to a new member of
this series on the basis of X-ray evidence.
The defensive secretions of termites have afforded an unusual group of diterpenoids. Spectral and X-ray crystallographic evidence has been presented for the
structure (87) assigned to a secotrinervitane which was
from Nasutitermes princeps. X-Ray crystallographic studies have also led to the structures of
some esters of the trinervitane alcohol (88) which were

from Nasutitermes havilandii. A methyl migration occurs during the formation of the tetracyclic diterpenoid 3a-hydroxyrippert- 15-ene (89) by Nasutitermes rippertii. The
structure was elucidated154by an X-ray analysis of the corresponding epoxyfrom the
acetate. An unrearranged tetracyclic diterpenoid (90) was
Malaysian nasute termite, Bulbitermes singaporensis.
Cleomeolide (9 1) is an unusual bicyclic diterpenoid
from Cleome
viscosa (Capparaceae). The Basidiomycetes contain a number of unusual terpenoid
metabolites such as the cyathins. These have now been thoroughly
W. H. Gerwick, W. Fenical, and M. U. S. Sultanbawa, J. Org. Chem., 1981, 46, 2233.
J. E.Hochlowski and D. J. Faulkner, Tetrahedron Lett., 1980, 21, 4055.
148 S. J. Selover, P. Crews, B. Tagle, and J. Clardy, J. Org. Chem., 1981, 46, 964.
lilQ E.L.Ghisalberti, P. R. Jefferies, and P. N. Sheppard, Tetrahedron, 1980,36, 3253.
150' K. D. Croft, E. L. Ghisalberti, P. R. Jefferies, and A. D Stuart, Tetrahedron, 1981, 37, 383.
151 K. D. Croft, E. L. Ghisalberti, P. R. Jefferies, D. G. Marshall, C. L. Raston, and A. H. White,
Aust. J. Chem., 1980, 33, 1529.
161
J. C. Braekman, D. Daloze, A. Dupont, J. Pasteels, B. Tursch, J. P. Declercq, G. Cermain,
and M. Van Meerssche, Tetrahedron Lett., 1980, 21, 2761; A. Dupont, J. C. Braekman, D.
Daloze, J. M. Pasteels, and B. Tursch, Bull. SOC.Chim. Belg., 1981, 90, 485.
153 G. D. Prestwich, S. G. Spanton, S. H. Goh, and Y. P. Tho, Tefrahedron Lett., 1981,22, 1563.
154 G. D. Prestwich, S. G. Spanton, J. W. Lauher, and J. Vrkoc, J. Am. Chem. SOC.,1980, 102,
146
147
6825
156
168
G. D. Prestwich, S. H. Goh, and Y. P. Tho, Experientia, 1981, 37, 11.

B. A. Burke, W. R. Chan, V. A. Honkan, J. F. Blount, and P. S. Manchand, Tefrahedron,
1980,36, 3489.
157
W. A. Ayer and L. M. Browne, Tetrahedron, 1981, 37, 2199.
203
Diterpenoids
Some aspects of the chemistry of lauren-1-ene, including the remote functionalization of other rings based on the I,-Pb(OAc), oxidation of laurenan-2-ols, have
been described.158 X-Ray crystallographic evidence has been presented for the
structure (92) of cinncassiol D,a pentacyclic diterpenoid from the dried bark of
Cinnamomum cassia possessing anti-complement activity.159
8 Diterpenoid Total Synthesis

Biomimetic cyclization of polyenes as routes to diterpenoids continues to be
explored. The brominative cyclization of geranyl-linalool afforded160the 3-bromomanoyl oxide and the boron trifluoride-catalysed cyclization of the diepoxide of
p-homogeranylanisole gave 13-methoxy-~-homo-4a-oxopodocarpatrienol Some
further synthetic studies of anhydroverticillol have been reported.162
A number of bicyclic diterpenoids have insect anti-feedant properties and consequently the synthesis of intermediates such as (93) in this series has attracted
CHO
OAc
(93)
158
i6@
l80
(94)
N. K. Nathu and R. T. Weavers, Aust. J. Chem., 1980, 33, 1589.

T. Nohara, Y. Kashiwada, T. Tomimatsu, M. Kido, N. Tokubuchi, and I. Nishioka, Tetrahedron Lett., 1980, 21, 2641.
T. Kato, K. Ishi, I. Ichinose, Y . Nakai, and T. Kumagai, J . Chem. Soc., Chem. Commun.,1980,
1106.
D. Nasipuri and A. K. Samaddar, Indian J . Chem., Sect. B, 1981, 20, 261.

m T. Kumagai, F. Ise, T. Uyehara, and T. Kato, Chem. Lett., 1981, 25.
181
(95)
204
attenti0n.1~~3-l~~
The total synthesis of dihydro-8-epiacrostalidic acid has been
reported.166
The synthesis of perhydrophenanthrenes related to tri- and tetra-cyclic diterpenoids has continued to be an active area.167Compound (94) has been synthesized
as a possible intermediate for the synthesis of cafestanone.168A synthetic approach
to diterpenoids with an abnormal trans-syn AB ring junction [e.g. (95)] has been
described.169The syntheses of 13-methoxypodocarpatrien- 19,20-dioic acid170 and
the 1l-hydroxyabieta-2,8,11, I3-tetraen- 1-one,l" isomeric with shonanol, have been
described.
AH
(97)
A
'
---CH,SiMe3
(99)
The biological activity of the diterpenoids of the aphidicolin-stemodin series

makes these compounds attractive targets. The total synthesis of stemodin (96)
has been described.172The key spiro-centre at C-9 was constructed by the internal
aldol condensation of the keto-aldehyde (97) to afford (98). Several stereoselective
syntheses of aphidicolin have been reported with different solutions to the problem
J. M. Luteijn, M. Van Doorn, and A. De Groot, Tetrahedron Lett., 1980, 21, 4127; J. M.
Luteijn and A. D e Groot, ibid., p. 4129
ltt4 J. M. Luteijn and A. D e Groot, Tetrahedron Lett., 1981, 22, 789.
le6 J. M. Luteijn and A. D e Groot, J . Org. Chem., 1981, 46, 3448.
I. H. Sanchez and J. C. Aranda, Tetrahedron Lett., 1980, 3655.
167 R. V. Venkateswaran, D. Mukherjee. and P. C. Dutta, J . Chem. Soc., Perkin Trans. I, 1981,
1603.
K. S. Maji, S. K. Mukhopadhyaya, D. Mukherjee, and P. C. Dutta, J . Chem. SOC.,Perkin

Tram. I, 1980, 2511.
l 8 9 F. Orsini and F. Pelizzoni, Gazz. Chim. Ital., 1980, 110, 499.
170 A. K. Banerjee and H. E. Hurtado, Heterocycles, 1981, 16, 613.
171 T.Matsumoto, S. Imai, and S. Yuki, Bull. Chem. SOC.
Jpn., 1981, 54, 1448.
172 E. J. Corey, M. A. Tius, and J. Das, J . Am. Chem. SOC.,1980, 102, 7612.
168
205
Diterpenoids
of creating the spiro-centre at C-9.173-175One procedure utilized the Claisen

rearrangement of the vinyl ether (99) to afford
The gibberellin plant hormones continue to attract synthetic attention. The
total synthesis of gibberellin A4 (101) by a more efficient route has been
and a major achievement has been the total synthesis of gibberellin A, (102) and
(101)
(102)
R
R
=H
= OH
gibberellic
The general strategy was based on a retrosynthetic analysis
which utilized the construction of the C-3-C-4 bond by an Aldol process (103),
the C-4-4-5 bond by a Michael process (104), and the C-I-C-10 bond by the
addition of a nucleophile to the enone (105). The latter was prepared from 1,7dimethoxynaphthalene (1 07) via (106).
173
l74
175
176
17?
R. E. Ireland, J. D . Godfrey, and S. Thaisrivongs, J . Am. Chem. SOC.,1981, 103, 2446.

R. L. Cargill, D . F. Bushey, J. R. Dalton, R. S. Prasad, R. D. Dyer, and J. Bordner, J . Org.
Chem., 1981,46,3389.
J. E. McMurry, A. Andrus, G. M. Ksander, J. H. Musser, and M. A. Johnson, Tetrahedron
Suppl., 1981, 9, 319.
A. L. Cossey, L. Lombardo, and L. N. Mander, Tetrahedron Lett., 1980, 21, 4383.
L. Lombardo, L. N. Mander, and J. V. Turner, J . Am. Chem. Sac., 1980,102,6626.
206
Several reports have appeared on the elaboration of other intermediates for

gibberellin synthesis.l 78J
The novel decipiadiene diterpenoid (1 08) has been synthesizedlS0and a report
has appeared on the synthesis of cubitene,lsl a monocyclic constituent of the termite
Cubitermes umratus.
G. Stork, W. C. Still, J. Singh, and S. Takei, Tetrahedron Lett., 1980, 21, 4051.
S. Takane, C. Kasahara, and K. Ogasawara, J . Chem. SOC.,Chem. Commun., 1981, 635.
180 M. L. Greenlee, J . Am. Chem. SOC.,1981,103,2425.
0.P.Vig. S.S. Bari, I. R. Teehan. and R. Vig, ZndianJ. Chem., Sect. B, 1980, 19, 446.
178
17*
4
Triterpenoids
BY R. B. BOAR
1 Introduction
This chapter follows the pattern of last years Report with the addition of a section
on Triterpenoid Saponins. The highlight of this years Report is undoubtedly the
total synthesis of dl-quassin by Grieco and his co-workers?
Reviews have appeared on the occurrence of triterpenoid saponins and sapogenins,2 the mass spectra of pentacyclic triterpenoids,s and the possible role of
triterpenoids as membrane component^.^ The plenary lectures from the 12th
IUPAC Symposium on the Chemistry of Natural Products have been p~blished.~
2 Squalene Group and Triterpenoid Biosynthesis
The biosynthesis of triterpenoids is discussed at some length in a new book.8 The
bacterium Acetobacter pasteurianum forms hopanoids such as diploptene (1) by
(1) R = H,
(4) R = H,
(5) R = H,a-OH
(2) R = H,a-OH
(3) R = H,B-OH
(6) R ==H,P-OH
cyclization of squalene. When a cell-free system was fed with the unnatural substrate (3RS)-squalene 2,3-epoxide, hop-22(29)-en-3a-ol (2) and -3p-01 (3) were
formed. Appropriate experiments established that the 3a-hydroxy-compound (2)
is derived from the (3R)-epoxide and the 3P-hydroxy-compound (3) from the
(3S)-epoxide. Similarly, a cell-free system from the protozoon Tetrahyrnena
pyriformis was shown to convert squalene into tetrahymanol (4) and (3R)- and
P. A. Grieco, S. Ferrino, and G. Vidari, J. Am. Chem. SOC.,1980, 102, 7586.
* R. S.Chandel and R. P. Rastogi, Phytochemistry, 1980, 19, 1889.
L. Ogunkoya, Phytochemistry, 1981, 20, 121.
W. D. Nes and E. Heftmann, J. Nat. Prod., 1981, 44, 377.
Pure Appl. Chem., 1981, 53, No. 6.
C. P. Manitto, Biosynthesis of Natural Products, Ellis Horwood Ltd., Chichester, 1981.
M. Rohmer, C. Anding, and G. Ourisson, Eur. J. Biochem., 1980, 112, 541.
207
208
(3s)-squalene 2,3-epoxides into gammacerane-3a,2la-diol (5) and -3p,2la-diol (6)

respectively.8 The single cyclase present in each of the above systems is clearly
rather primitive as regards substrate specificity. The stereospecifically labelled
squalene (7) and (3RS)-squalene 2,3-epoxide (8) were synthesized and fed to the
cell-free system from T. pyriforrnis. Examination of the IH n.m.r. spectra of the
derived triterpenoids (4), (9,and (6) showed that (4) and (6) arise via cyclization
of an all-chair conformation of squalene (7) and (3s)-epoxide (8) respectively (4a
and 228 methyls labelled in each case), but that (5) arises from the (3R)-epoxide
(8) with a boat-chair-chair-chair-chair folding (4p and 22p methyls labelled)
(Scheme 1).8
HO
The bacterium Methylococcus capsulatus is unique among prokaryotes in that it

produces not only hopanoids but also lanosterol derivatives. Evidence for the
' P. Bouvier, Y . Berger, M. Rohmer, and G. Ourisson, Eur. J . Biochem., 1980,112, 549.
Trit erpenoids
209
(9) R = H2
(10) R = H,P-OH
(11) R = H,a-OH
presence of two separate cyclases has now been obtained. A cell-free preparation
from M . capsulatus converted squalene into diploptene (1) [but not into 5a-lanosta8,24-diene (9)], (3S)-squalene 2,3-epoxide into hop-22(29)-en-3p-ol (3) and lanosterol (lo), and (3R)-squalene 2,3-epoxide into hop-22(29)-en-3a-o1 (2) and
3-epilanosterol(ll). In that it does not reject the (3R)-epoxide, the squalene epoxide
cyclase is less specific than that present in typical e~karyotes.~
Details have been published of the biosynthesis of olean-12-ene and urs- 12-ene
type triterpenoids in tissue cultures of Isodon japonicus (Labiatae).lo The results
are fully in accord with the original biogenetic postulates of Ruzicka and his
colleagues.11 By using [5-13C, 5-2H2]MVAas substrate it was shown that, as expected, both squalene 2,3-epoxides [part structures (12) and (13)] are involved in
the biosynthesis of 2a-hydroxyursolic acid (14), 3-epimaslinic acid (13, and
p-sitosterol in I. japonicus. The 13C n.m.r. spectra of (14) and (15) suggested
Jvu
Jvu
(14)
(15)
additionally that in the olean-12-ene series the double bond is formed by elimination
of the 12a-H, but that in the urs-12-ene series it is the 12p-H that is lost.12
It has been shown that the hydrogen migration from C-24 to C-25 that occurs
during the biosynthesis o f isofucosterol in Pinus pinea (Pinaceae) occurs such that
lo
l2
M. Rohmer, P. Bouvier, and G. Ourisson, Eur. J . Biochem., 1980, 112, 557.

S. Seo, Y. Tomita, and K. Tori, J. Am. Chem. SOC.,1981,103,2075.
A. Eschenmoser, L. Ruzicka, 0. Jeger, and D. Arigoni, Hefv. Chim. Acra, 1955, 38, 1890.
S. Seo, Y. Tomita, K. Tori, and Y. Yoshimura, J . Chem. SOC.,Chem. Commun., 1980, 1275.
210
(16)
(17)
the pro-E methyl group of the precursor (16) becomes the pro-R methyl group of
isofucosterol [as (1 7)].13 24-Methyl-25-azacycloartanol (1 8) has been synthesized.
It acts as a potent inhibitor of C-24 methyltransferase in higher plant cells.14 It is
more potent than 25-azacycloartanol (1 9).15 The effects of various triterpenoids
on the growth of the fungus Phytophthora cactorum have been investigated.16.The
enzymic preparation of [14C]-labelled squalene from [2-14C]MVA has been
described.l
(18) R = Me
(19) R = H
3 Fusidane-Lanostane Group
The bark of Pinus monticolu (Pinaceae) contains many triterpenoids of the lanostane
and serratane groups. Of these, the lanost-9(1 I)-enes (20)-(27) are new natural
products (see also Section 9).lS The sea cucumber Stichopus chloronotus affords a
series of antifungal oligoglycosides which on enzymatic hydrolysis yield the genuine
sapogenins stichlorogenol(28) and 25,26-dehydrostichlorogenol(29).The structure
and stereochemistry of (28) were confirmed by X-ray analysis. Acid hydrolysis of
the saponins gave artefact sapogenins containing the 8-ene or 9( I 1)-ene system.lg
Other sea cucumbers contain oligoglycosides based on the sa?ogenins (30) and (31)
(Bohadschia bivittata)20 and (32) (Actinopyga echinites).21Two further 27-nortril3
l4
l6
l8
l7
l8
l9
21
F. Nicotra, F. Ronchetti, G. Russo, G. Lugaro, and M. Casellato, J. Chem. SOC.,Perkin

Trans. I , 1981, 498.
A. S. Narula, A. Rahier, P. Benveniste, and F. Schuber, J. Am. Chem. SOC.,1981, 103, 2408.
P. Schmitt, A. S. Narula, P. Benveniste, and A. Rahier, Phytochemistry, 1981, 20, 197.
W. D. Nes and G. W. Patterson, J. Nut. Prod., 1981, 44, 215.
G. Sandmann, W. Hilgenberg, and P. Boeger, Z. Naturforsch., Teil C,1980, 35, 927.
J. P. Kutney, G. Eigendorf, B. R. Worth, J. W. Rowe, A. H. Conner, and B. A. Nagasampagi,
Helv. Chim. Acta, 1981, 64, 1183.
I. Kitagawa, M. Kobayashi, T. Inamoto, T. Yasuzawa, Y. Kyogoku, and M. Kido, Chem.
Pharm. Bull., 1981, 29, 1189.
I. Kitagawa, M. Kobayashi, M. Hori, and Y. Kyogoku, Chem. Pharm. Bull., 1981, 29, 282.
I. Kitagawa, T. Inamoto, M. Fuchida, S. Okada, M. Kobayashi, T. Nishino, and Y . Kyogoku,
Chem. Pharm. Bull., 1980,28,1651.
21 1
Trit erpenoids
RO
(22) R
(23) R
(20) R = Me
(21) R = H
As (20)
Me
H
{p
(26) OH at C-22 or C-23

(24) R
(25) R
= Me (24s)
= H (24Q
(28)
(29) 25,26-dehydro
terpenoids from Muscari comosum (Liliaceae) have the interesting structures (33)
and (34).22 Polyporenic acid D (35) is a new natural product from Polyporus
oficinalis (P~lyporaceae).~~
The cytotoxicity of various lanosterol derivatives
isolated from the fungus Poria cocos (Polyporaceae) has been inve~tigated.~~
5cc-Lanost-S-en-24-one [as (36)] has been converted into 5a-lanost-S-en-23-one
[as (37)J in 21 % overall yield (Scheme 2). A similar sequence was successfully
applied to 29-nor-5a-lanost-9( 1l)-en-24-0ne.~~A series of 9,ll -epoxy-7-ketolanostane derivatives with degraded side chains has been synthesised,26as has a
range of side-chain modified lanosterol analogue^.^' Details have been reported
21
M. Parrilli, R. Lanzetta, M. Adinolfi, and L. Mangoni, Tetrahedron, 1980,36, 3591. See also,
M. Parrilli, R. Lanzetta, V. Dovinola, M. Adinolfi, and L. Mangoni, Can. J . Chem., 1981, 59,
2261.
2s
2p
25
86
27
R. K. Thappa, S. G. Agarwal, K. L. Dhar, and C. K. Atal, Phytochemistry, 1981, 20, 1746.

J. Valisolalao, L. Bang, J.-P. Beck, and G. Ourisson, BUN.SOC.Chim. Fr., 1980, 473.
M. Namikawa, T. Murae, and T. Takahashi, Chem. Lett., 1981, 733.
Z. Paryzek and R. Wydra, Monatsh. Chem., 1980, 111, 1427.
Y . Sat0 and Y . Sonoda, Chem. Pharm. Bull., 1981,29, 356.
212
HO
(30) R1 = R2= H
(31) R1= OH, R2= H
(32) R' = R2= OH
(33) R = H,P-OH
(34) R = 0
<vii, viii
+ &
~
v, vi
Me0
(37)
Reagents: i, LDA; ii, Ph,S,; iii, Pb(OAc),; iv, MeOH-I,; v, LiAlH,;
vi, HCI; vii, Ac,O; viii, Ca-liq. NH,
Scheme 2
Triterpenoids
213
of the efficient dehydrogenation of steroidal and triterpenoid ketones using

benzeneseleninic anhydride.28 The absolute configurations at C-24 of the 24,25dibromides A and B derived from 5a-lanosta-8,24-dien-3p-yl
acetate have been
reversed.29
Further new natural products are (38) from the toxic micro-organism Fusarium
triphyllol (41) from Adenosporotrichioides 92Z,30(39) and (40) from olive
and cyclonervilol (42) and cyclohomonervilol
phora triphyh (Campan~laceae),~~
(43) from Nerviliapurpurea (Orchidaceae). The structure of (43)was supported by
its conversion into cycloeucalenol.33Two new xylosides from Cimicifuga japonica
(Ranunculaceae) are based on the genuine sapogenins (44) and (45). Treatment of
(43)
OH
(47)
(45) R = OH
(46) R = H
30
31
s2
83
D. H. R. Barton, D. J. Lester, and S. V. Ley, J . Chem. SOC.,Perkin Trans. 1, 1980, 2209.

R. M. Carman and B. N . Venzke, Aust. J . Chem., 1981,34,679.
B. Yagen, P. Horn, A. Z . Joffe, and R. H. Cox, J. Chem. SOC.,Perkin Trans. I , 1980, 2914.
T. Itoh, K. Yoshida, T. Yatsu, T. Tamura, T. Matsumoto, and G. F. Spencer, J. Am. Oil
Chem. SOC.,1981,58, 545.
C. Konno, T. Saito, Y. Oshima, H. Hikino, and C. Kabuto, Plunta Med., 1981, 42, 268.
T. Kikuchi, S. Kadota, H. Suehara, and T. Namba, Tetrahedron Lett., 1981, 22, 465.
214
(44) with sulphuric acid in aqueous methanol gave cimigenol (46).34 Cyclosadol
(47) from Zea mays (Gramineae) has been shown by n.m.r. spectroscopy to have
the 23E c ~ n f i g u r a t i o n3.1-Norcycloswietenol(48)
~~
has been isolated from Swietenia
mahagoni (Meliaceae) heartwood.36 The assigned structure is supported by 13C
n.m.r. spectral data.37The ketone (49), itself readily available from cycloartenol,
has been converted into the Buxus alkaloid, cyclobuxophylline-M (50).38
The seed oil of Cucumissativus (Cucurbitaceae) contains (51) and (52) in addition
Momordicosides A-E from the seeds
to other known 4a-methyl
of Mornordica charantia (Cucurbitaceae) are based on the sapogenins (53)-(56).
The structure and stereochemistry of compound (53) were established by X-ray
analysis.4oThese cucurbitacins are notable for the absence of an oxygen function
(51) R
(52) R
Me, 8,9-ene
H, 7,8-ene
OH
OH
H
=
..*
~ v n
As (53)
As (53)
(54)
34
35
36
37
38
39
I0
OH
yCHO
As (53)
(55)
(56)
N. Sakurai, 0. Kimura, T. Inoue, and M. Nagai, Chem. Pharm. Bull., 1981, 29, 955.
T. Itoh, N. Shimizu, T. Tamura, and T. Matsumoto, Phytochemistry, 1981, 20, 1353.
A. S. R. Anjaneyulu, V. Lakshminarayana, Y. L. N. Murty, and L. R. Row, Indian J . Chem.,
1979,17B, 423.
V. Lakshminarayana, Y . L. N. Murty, and L. R. Row, Org. Magn. Reson., 1981, 17, 77.
M. C . Desai, J. Singh, H. P. S . Chawla, and S . Dev, Tetrahedron, 1981, 37, 2935.
T. Itoh, Y. Kikuchi, N. Shimizu, T. Tamura, and T. Matsumoto, Phytochemistry, 1981, 20,
1929.
H. Okabe, Y. Miyahara, T. Yamauchi, K. Miyahara, and T. Kawasaki, Chem. Pharm. Bull.,
1980,28,2753; Y. Miyahara, H. Okabe, and T. Yamauchi, ibid., 1981,29, 1561.
215
Triterpenoids
at C-1 1, as is lOa-cucurbita-5,24-dien-3P-o1
which has now been isolated from
seedlings of Bryonia dioica (Cu~urbitaceae).~'
The biogenesis of the cucurbitacins
has been discussed.*l
4 Dammarane-Euphane Group
The bark of Rhus javanica (Anacardiaceae) contains rhuslactone (57), a novel
dammarane-type triterpenoid with an a-oriented side chain. The structure followed
@
p
HO
HO=*
(58)
(57)
(59) 24,25-dihydro
OH
(61)
(62) 24,25-dihydro
from X-ray analysis of the derived tri01.~~
Acid hydrolysis of the saponin of
Emmenospermum pancherianum (Rhamnaceae) affords ebelin lactone (58) together
with 24,25-dihydroebelin lactone (59) and the novel D-homo aromatic triterpenoid
(60). All three compounds are artefacts since Smith-de Mayo degradation of the
saponin affords the genuine, acid-labile, sapogenins jujubogenin (6 1) and dihydrojujubogenin (62).43The saponins of Zizyphus jujuba (Rhamnaceae) are also based
on j ~ j u b o g e n i n Other
. ~ ~ dammaranes reported this year are vellozone [(20R)-20hydroxy-24-methylenedammar-3-one]from VeZlozia stipitata (Vell~ziaceae),~~
41
42
44
45
L. Cattel, G. Balliano, 0. Caputo, and F. Viola, Planta Med., 1981, 41, 328.
C.-K. Sung, T. Akiyama, U. Sankawa, Y. Iitaka, and D.-S. Han, J. Chem. Soc., Chem.
Commun., 1980,909.
G. V. Baddeley, J. J. H. Simes, and T.-H. Ai, Aust. J. Chem., 1980, 33, 2071.
N. Okamura, T. Nohara, A. Yagi, and I. Nishioka, Chem. Pharm. Bull., 1981, 29, 676.
A. C. Pinto, P. M. Baker, B. Gilbert, R. Pinchin, F. A. M. Reis, M. S. Waineraich, and
D. H. T. Zocher, Phytochemistry, 1980, 19, 2486.
216
(20S)-damrnar-24-ene-20(,3p, 12p,20-tetraol from Gynostemma pentaphyllum (Cucurb i t a ~ e a e ) ,(20S724S)-20,24-dihydroxydammar-25-en-3-one

~~
from Betula mandschurica (Bet~laceae),~'
the (20S724R)-20,24-ethers (63)-(66) from B. lanata,48
and (20S)-dammar-24-ene-3a,17a,20-triol plus the ethers (67)-(69) from various
HO
6
R'
(63)
(64)
(65)
(66)
R1= H,a-OH, R2= Ac

R1= H,a-OAc, R2= H
R1= 0, R2 = H
R1= H,a-OH, R2 = H
(67) R' = H,a-OH, R2= H,, R3= H,P-OH, R4= OH

(68) R' = H,B-OH, R2= H,P-OAc, R3= Hz, R4= H
(69) R' = R2 = H,P-OH, R3= HQ,R4= H
Betula species.49The efficient conversion of (20S,24R)-20,24-epoxydammarane-3a,

12$,25-triolinto the 25-O-p-~-glucosidehas been reported.50The seed oil of Cacalia
atriplicifolia (Compositae) is a rich source of esters of dammarenediol II.61
New tirucallane triterpenoids are adenophorate (70) (X-ray analysis) from
Adenophora triphylla (Campan~laceae),~~
and the ring A seco derivatives (71) and
(72) from Guarea cedrata (Melia~eae].~~
Treatment of the 7a-hydroxy- or 7-ketoapotirucall- 14-enes (73)-(75) with monoperphthalic acid affords the corresponding
14a,15a-epo~ides.~~
(70)
46
47
48
48
50
51
52
53
(71) R
(72) R
=H
= Me
M. Nagai, K. Izawa, S. Nagumo, N. Sakurai, and T. Inoue, Chem. Pharm. Bull., 1981,29,779.
G. V. Malinovskaya, V. L. Novikov, V. A. Denisenko, and N . 1. Uvarova, Khim. Prir. Soedin.,
1980, 346; English translation, Chem. Nat. Compoundr, 1980,16, 257.
N. D. Pokhilo, G . V. Malinovskaya, V. V. Makhan'kov, V. F. Anufriev, and N. I. Uvarova,
Khim. Prir. Soedin., 1980, 513; English translation, Chem. Nat. Compounds, 1980, 16, 368.
G. V. Malinovskaya, N. D. Pokhilo, V. V. Isakov, and N. I. Uvarova, Chem. Abstr., 1980, 93,
220 945.
L. N. Atopkina and N.I. Uvarova, Khim. Prir. Soedin., 1980,205; English translation, Chem.
Nut. Compounds, 1980, 16, 159.
G. F. Spencer, J . Nat. Prod., 1981, 44, 166.
J. A. Akinniyi, J. D. Connolly, D. S. Rycroft, B. L. Sondengam, and N. P. Ifeadike, Can. J .
Chem., 1980,58, 1865.
A . Merrien, B. Meunier, C. Pascard, and J. Polonsky, Tetrahedron, 1981, 37, 2303.
217
Triterpenoids
(73)R1 = H,@-OAc,R2= H,a-OH

(74) R1 = 0,R2= H,a-OH
(75)R1= R2= 0
Tetranortriterpen0ids.-The cytotoxic or insect antifeedant activity shown by
various tetranortriterpenoids ensures that the isolation and structure determination
of these often complex molecules continue to attract attention. A detailed examination of the seeds of Azadirachta indica (Meliaceae) has yielded the further tetranortriterpenoids (76)-(8 1). The stereochemistry of 7-acetylneotrichilenone (78)
OAc
a
OAc
(77)
21 8
was confirmed by X-ray analysis.54 Seed oil of A . indica gave three compounds
with insect antifeedant activity-3-deacetylsalannin (82), salannol (83), and the
known 1,3-diacetylvilasinin (see Vol. 10, p. 145).55The fruit of Melia azedarach
(Meliaceae) contains ohchinolides A and B (see Vol. 11, p. 117), nimbolidins A
(82) R
(83) R
(84) R = COPh
(85) R = tiglate
= tiglate
= COCH,CHMe,
~o
AcO"'
"OTig
'*,a
(86) R = AC
(87) R = H, (12R)
(84) and B (85), nimbolinin B (86), and 1-deacetylnimbolinin (87).56 Trichilins

A-D, insect antifeedants from the root bark of Trichilia roka (Meliaceae), have
structures (88)-(91) respectively. This paper provides a fine example of the potential of modern chromatographic and spectroscopic (particularly n.m.r.) techniques.
In the presence of traces of acid, trichilin A (88) rearranges to C (90). Treatment
AcO-..
As (88)
"OH
0
(88) R
(89) R
(91) R
64
56
58
=
=
=
H,P-OH
H,a-OH
H2
W. Kraus, R. Cramer, and G. Sawitzki, Phytochernistry, 1981, 20, 117

W. Kraus and R. Cramer, Liebigs Ann. Chern., 1981, 181.
W. Kraus and M. Bokel, Chern. Ber., 1981,114,267.
Triterpenoids
219
AcO"'
OAc
0
I
(94)
(95) R1= Me, R2= Ac

(96) R1= CH,OH, R2= COCHOHCHMe,
of trichilin B (89) with zinc borohydride induced an unexpected acetyl migration

which resulted in the formation of aphanastatin (92).57 The X-ray structural
analyses of aphanastatin (92) and related compounds from Aphanamixis grandifolia (Meliaceae) have now been reported.58Seeds of T . dregeana contain dregeanas
1-5 for which the structures (93)-(97) respectively have been deduced.59Continued investigation of T. hispida has resulted in the elucidation of structures
(98)-(100) for the cytotoxic hispidins A-C respectively.60Hispidin C (100) is
thus identical to the compound previously isolated from Aphanamixis polystacha
(see Vol. 10, p. 150). 2'-Hydroxyrohitukin has been isolated from Guarea cedrata.52
The bark of Toona ciliata (Meliaceae) has yielded two further ring B seco tetranortriterpenoids (101) and (102) which have insect antifeedant activity.61
57
68
69
6o
M. Nakatani, J. C. James, and K. Nakanishi, J . Am. Chem. SOC.,1981, 103, 1228.

B. Arnoux and C. Pascard, Acta Crystallogr., Sect. B, 1980, 36, 2709.
D. A. Mulholland and D. A. H. Taylor, Phytochemistry, 1980, 19, 2421.
S. D. Jolad, J. J. Hoffmann, K. H. Schram, J. R. Cole, M. S. Tempesta, and R. B. Bates,
J . Org. Chem., 1981, 46, 641.
W. Kraus and W. Grimminger, N o w . J . Chem., 1980, 4, 651.
220
(99) R = tiglate
(100) R = A c
fi0
H
*cO
b: OH
0
"OH
7
p
"=/p
HO
Triterpenoids
22 1
0
H
C0,Me
h1
?H
As (111)
(113)
(111) R
(112) R
C(OH)Me,
=H
Further new natural limonoids are tecleanin (103), 7-deacetylproceranone (104),

and 7-deacetylazadirone (105) from Teclea grandifolia (Rutaceae),62 7a,ll pdiacetoxydihydronomilin (1 06) from Cedrela mexicana (Melia~eae),~~
proceranolide
(107y4 and proceranone (108y5 from Carapa procera (Meliaceae), isolimonic acid
(109) from Citrus aurantium (Rutaceae),66and methyl deacetylnomilinate (1lo),
calamin (1 1l), retrocalamin (1 12), cyclocalamin (1 13), and methyl isoobacunoate
diosphenol (114) from C. reti~ulata.~
Chromatography of calamin (111) on a
silica gel column induced the formation of retrocalamin (1 12) via a retro-Aldol
rea~tion.~
Investigation of the possible synthesis of limonin from a steroidal starting
material has led to the preparation of the model compound (115).se
62
83
84
85
J . F. Ayafor, B. L. Sondengam, J. D. Connolly, D. S. Rycroft, and J. I. Okogun, J . Chem.

Soc., Perkin Trans. 1, 1981, 1750.
G. B. Marcelle and B. S. Mootoo, Tetrahedron Left., 1981, 22, 505.
B. L. Sondengam, C. S. Kamga, and J. D. Connolly, Phytochemistry, 1980,19, 2488.
B. L. Sondengam, C. S. Kamga, S. F. Kimbu, and J. D. Connolly, Phytochemistry, 1981, 20,
173.
86
68
R. D. Bennett and S. Hasegawa, Phytochemistry, 1980, 19, 2417.

R. D. Bennett and S. Hasegawa, Tetrahedron, 1981, 37, 17.
G. Emmer and W. Graf, Helv. Chim. Acta, 1981, 64, 1398.
222
0
' 0
OH
Pentanortriterpenoids.-Azadirachta indica, a rich source of tetranortriterpenoids,

has now afforded the pentanor-compounds nimbinene (1 16), 6-deacetylnimbinene
(1 17), nimbandiol (1 1S), and 6-O-acetylnimbandiol (1 19).69
(116) R = A c
(117) R = H
(118) R
(119) R = A c
Quassinoids.-Soulamea muelleri (Simaroubaceae) has yielded soulameanone (1 20),

1,12-di-O-acetylsoulameanone(121), and A2-picrasin B (122). The structure of
(120) was established by X-ray analysis. Treatment of (122) with diazomethane
afforded quassin. 70 Other new quassinoid natural products reported this year are
~~
soularubinone (123), an antileukaemic compound from S . t o m e n t o ~ a ,13,18OMe
0
H
.
H
(120) R = H
(121) R = AC
W. Kraus and R. Cramer, Chem. Ber., 1981, 114, 2375.

J. Polonsky, M. Van Tri, T. Prange, C. Pascard, T. Sevenet, and J. Pusset, Tetrahedron, 1980,
36, 2983.
71 M . Van Tri, J. Polonsky, C. Merienne, and T. Sevenet, J . Nat. Prod., 1981, 44, 279.
6B
'O
Triterpen oids
223
dehydroexcelsin (124) from Ailanthus excelsa (Simaroubaceae),72 and dehydrobruceine A (125) and dihydrobruceine A (I 26) from Brucea javanica (Simaroubaceae).73
Grieco and his co-workers have completed a most notable total synthesis of
dl-quassin (130) (Scheme 3).l The synthesis of the hydroxy-lactone (127) was
outlined last year (see Vol. 1 1 , p. 121). The conditions developed for the conversion
of the bis-(cc-hydroxy-ketone) (1 28) into the bis-(O-methyldiosphenol)(1 29) also
achieved the crucial inversion of configuration at C-9.74The close proximity of
the C-7 oxygen atom to the C-11 carbon atom in the 9-epiquassin skeleton is
evident from a series of reactions in which intramolecular participation occurs.
Thus, for example, treatment of the epoxide (131) with lithium aluminium hydride
gave the ether (132) whose structure and stereochemistry were established by X-ray
analysis.75Synthesis of the tetracyclic (133), a possible intermediate for quassinoid
synthesis, involved the intramolecular cycloaddition of a quinonedimethane as the
key step.76
Various workers have attempted the chemical 77-80 or microbiologica181 modification of quassinoids in the search for compounds with potent antileukaemic
activity.
73
74
75
7e
77
78
78
S . A. Khan and K. M. Shamsuddin, Phytochemistry, 1980, 19, 2484.

J. D. Phillipson and F. A. Darwish, Planta Med., 1981, 41, 209.
P. A. Grieco, S . Ferrino, G. Vidari, and J. C. Huffman, J . Org. Chem., 1981, 46, 1022.
P. A. Grieco, S . Ferrino, G . Vidari, J. C . Huffman, and E. Williams, Tetrahedron Lett., 1981,
22, 1071.
T. Kametani, M. Chihiro, T. Honda, and K. Fukumoto, Chem. Pharm. Bull., 1980, 28, 2468.
T. Murae and T. Takahashi, Bull. Chem. SOC.Jpn., 1981, 54, 941.
N. Khoi and J. Polonsky, Helv. Chim. Acta, 1981, 64, 1540.
C . G. Casinovi, G. Fardella, G. Grandolini, and C . Burinato, Farmaco, Ed. Sci., 1981,36, 116.
M. Okano and K.-H. Lee, J . Org. Chem., 1981,46, 1138.
M. M. Chien and J. P. Rosazza, J . Chem. Sac., Perkin Trans. I , 1981, 1352.
224
viii, ix
&
OMe
Me0
! H
OMe
x,xi
MeO&o
OMe
j H
Reagents: i, Bu',AIH; ii, MeOH-H+; iii, B2H,; iv, H,O,-OH-;

v, Collins reagent; vi, LDA; vii, Moo,-pyridine-HMPA ;
viii, MeOH-MeO--DMSO; ix, MeI; x, aq. HOAc;
xi, Fetizon's reagent
Scheme 3
Me0
OMe
OMe
Me
225
Triterpenoids
5 Lupane Group
X-Ray analysis of the new triterpenoid ( 1 34) from Emmenospermum pancherianum

(Rhamnaceae) indicated that the isopropenyl group has the unusual P-configura t i ~ n Subsequent
.~~
reinvestigation of emmolactones2 by X-ray analysis showed
that it also has a p-isopropenyl group, and its structure is therefore revised to
(135).43 Other lupane natural products reported this year are lupa-5,20(29)-diennepeticin (lup-20(29)-ene3p-01 from Holarrhena antidysenterica (Apo~ynaceae),~~
3p, 11a-diol) from Nepeta hindostana (Labiatae),84 3p-hydroxylup-20(29)-en-30-al
-OH
HY,
8
J.
Me0,C
Me0,C
(136) R = H,P-OH
(137) R = H,p-OAc
(138) R = 0
from Lychnophora unij7ora ( C o m p ~ s i t a e ) ,lup-20(29)-ene-3p,

~~
16p,28-triol from
Stenocereus thurberi (Cactaceae),86 and compounds (1 36)-( 138) from Salvia
phzomoides (Labiatae). 8 7 Methyl 3,4-secolup-20(29)-en-3-oate(139), reported last
year as a component of certain .sedirnentsys8has now been found in Caralluma
buchardii (Asclepiadaceae).8 9 Neolupenyl acetate (1 40) and tarolupenyl acetate
(141) and the corresponding alcohols have been isolated from the dried roots of
Taraxacum japonicum (Compositae).
R. A. Eade, J. Ellis, and J . J. H. Simes, Aust. J . Chem., 1967, 20, 2737.
C. R. Narayanan and D. G. Naik, Indian J . Chem., Sect. B, 1981, 20, 62.
1 3 ~V. U. Abmad, S. Bano, W. Voelter, and W. Fuchs, Tetrahedron Leu., 1981, 22, 1715.
85 F. Bohlmann, L. Muller, R. M. King, and H. Robinson, Phytochemistry, 1981, 20, 1149.
B6 H. W. Kircher, Phytochemistry, 1980, 19, 2707.
8 7 M. C. Garcia-Alvarez,G. Savona, and B. Rodriguez, Phytochemistry, 1981, 20, 481.
8 8 B. Corbet, P. Albrecht, and G. Ourisson, J . Am. Chem. SOC.,1980, 102, 1171.
8 9 V. A. Castro, C. Garcia, A. G. Gonzalez, R. Hernandez, and E. Suarez, Phytochemistry, 1980,
82
83
19, 2210.
H. Ageta, K. Shiojima, K. Masuda, and T. Lin, Tetrahedron Lett., 1981, 22, 2289.
226
(14)
(141)
Details have appeared of the synthesiss1 and rearrangements2 of 3a,4a- and
3P,4p-epoxy-~:A-friedo-l8P,19cr-H-lupanes (see Vol. 1 1, p. 123). Wagner-Meenvein
type rearrangements of some lupane derivatives have been
The I3C
n.m.r. spectra of some lupanes have been reported. s4
6 Oleanane Group
The confusingly named periandric acid I1 (142) and periandric acid IV (143) are
the aglycones of periandrins 11 and IV respectively, sweet glycosides from Periundra
dulcis (Leguminosae).s5 Other new olean- 12-ene natural products are 16p-hydroxy3-0x0-olean-12-en-28-oicacid and 16~-hydroxy-3-oxo-oleana1,12-dien-28-0icacid
from grape peel, 96 canthic acid (3p,7p-dihydroxyolean-12-en-28-oic acid) from
Canthiurn dicoccum (Rubia~eae),~'
and bartogenic acid (2a,3p, 19a-trihydroxyolean12-ene-24,28-dioic acid) from Burringtoniu speciosa (Lecythadaceae).D8 Napoleogenol (see Vol. 11, p. 126) is now considered to be identical to aescigenin
(16cc,2l0c-epoxyolean-12-ene-3~,24,28-tri01).~~
The unusual structure (144) has been
proposed for salviolide from Sulviu rnexicunu (Labiatae).lo0 X-Ray analysis of
methyl morolate acetate (145) has been reported.lof
The friedelanes (146)-( 148) have been isolated from Cutha cussinoides (Celastraceae). The structure and stereochemistry of (147) were proved unambiguously
by X-ray analysis of the corresponding acetate.lo2Structure (147) had previously
been assigned to octandronal (see Vol. 4, p. 214), a compound with different
91
O2
O3
Y. Yokoyama, Y.Moriyama, T. Tsuyuki, T. Takahashi, A. Itai, and Y. Iitaka, Bull. Chem.

SOC.Jpn., 1980, 53, 2971.
Y . Yokoyama, Y. Moriyama, T. Tsuyuki, and T . Takahashi, Bull. Chem. Soc. Jpn., 1981, 54,
234.
A. S. R. Anjaneyulu, M. N. Rao, A. Sree, and V. S . Murty, Indian J. Chem., Sect. B, 1980, 19,
735.
O4
R. C. Carpenter, S . Sotheeswaran, M. U. S. Sultanbawa, and B. Ternai, Org. Mugn. Reson.,
1980, 14, 462.

Y . Hashimoto, H. Ishizone, and M. Ogura, Phytochemistry, 1980,19,2411.
g* C. H. Brieskorn and G. Blosczyk, Z . Lebensm.-Unters.Forsch., 1981, 172, 201.
$'
T. K. Chatterjee, A. Basak, A. K. Barua, K. Mukherjee, and L. N. Roy, Trans. Bose Res. Inst.
(Calcutta), 1979, 42, 85.
O 8 G. S. R. Subba Rao, S . Prasanna, V. P. S. Kumar, and G. R. Mallavarapu, Phytochemistry,
1981, 20, 333.
M. Kapundu, R. Warin, C. Delaude, and R. Huls, Bull. SOC.Chim. Belg., 1980, 89, 1001.
loo 0. Collera, E. Gomora, and F. G. Jimenez, Rev. Latinoum. Quim., 1980, 11, 60.
lol J. R. Cannon, B. W. Metcalf, C . L. Raston, and A. H. White, Aust. J. Chem., 1981, 34, 1135.
lo2 C. Betancor, R. Freire, A. G . Gonzalez, J. A. Salazar, C. Pascard, and T. Prange, Phytochemistry, 1980, 19, 1989.
95
227
Triterpenoids
HO
(142) R
(143) R
(147) R
(148) R
= CHO
= CH,OH
CH20H
= CO,H
(149) R = H,
(150) R = 0
physical and spectral properties. It follows that the structures of octandronal and
the related octandronic acid require revision. Other new friedelanes include kokzeylanol (149) and kokzeylanonol (150) from Kokoona zeylanica (Celastraceae),lo3
lp-hydroxyfriedel-6-en-3-onefrom Momordica foetida (Cucurbitaceae),lo4and
3 p-hydroxyfriedelan-7-onefrom Pergularia extensa (As~lepiadaceae).~~~
Following
the X-ray analysis of compound T, the structures of triterpenoids Q, T, and U
from Sulacia prinoides (Hippocrateaceae) have been revised to (151)-( 153)
respective1y.lo6The X-ray analysis of salaspermic acid has been p~b1ished.l~~
Io3
A. A, L. Gunatilaka, N. P. D. Nanayakkara, and M . U. S . Sultanbawa, Tetrahedron Lett.,

1981,22, 1425.
Io5
A. A. Olaniyi, Planta Med., 1980, 40, 303.

B. Talapatra, A. Basak, S.Goswami, and S . K. Talapatra, Indian J . Chem., Sect. B, 1981, 20,
lo6
D. Rogers, F. L. Phillips, B. S. Joshi, and N . Viswanathan, J . Chem. SOC.,Chem. Commun.,
lo'
D. Rogers, K. A. Woode, N. Viswanathan, and B. S . Joshi, J . Chem. SOC.,Chem. Commun.,
lo*
249
1980, 1048.
1980, 1049.
228
(151) R
(152) R
(153) R
= CHO
= CH,OH
= COzH
Zeylasterone (154) is a novel phenolic 24-norfriedelane from K. zeylanica.los

Isoiquesterin (1 55) from Sulaciamadugus~ariensis~~~
and (156) from S . macrosperma
are new quinone methides.l1 The biogenesis of triterpenoid quinone methides has
been discussed.lll
Isomultiflorenol (157) co-occurs with cucurbitacins in seedlings of Bryonia
d i o i ~ aThe
. ~ ~derivatives (158) and (159), both of which show diuretic activity in
rats, occur in Antidesma menusu (Euphorbiaceae).l123cr-Hydroxymultiflora-7,9(11)dien-29-oicacid occurs in the roots of B. dioica as the p-hydroxycinnamateester.l13
The compounds (160),114 (161),115 and (162)116 have been prepared as possible
intermediates for pentacyclic triterpenoid synthesis. Treatment of oleana-l2,15diene-3p,28-diol 3-acetate with toluene-p-sulphonyl chloride in pyridine affords
the ~(16a)-homocompound (163). The mechanisms of this and related reactions
are discussed.l172a,3p-Diacetoxy-28-noroleana12,17-diene has been synthesized.lls
lo8
loQ
110
ll1
112
113
11*
115
ll6
11'
118
G.M.K.B. Gunaherath, A. A. L. Gunatilaka, M . U. S. Sultanbawa, and M. I. M. Wazeer,

A. T. Sneden, J . Nut. Prod., 1981, 44,503.
G. C. S. Reddy, K. N. N. Ayengar, and S . Rangaswami, Indian J . Chem., Sect. B , 1981,20,197.
J. P. Kutney, M. H. Beale, P. J. Salisbury, K. L. Stuart, B. R. Worth, P. M. Townsley, W. T.
Chalmers, K, Nilsson, and G . G. Jacoli, Phytochemistry, 1981, 20, 653.
S. H. Rizvi, A. Shoeb, R. S. Kapil, and S. P. Popli, Phytochemistry, 1980, 19, 2409.
P. J. Hylands, E.-S. S. Mansour, and M. T. Oskoui, J . Chem. Soc., Perkin Trans. I , 1980,2933.
J. W. ApSimon, A. M. Greaves, N.-D. Tho, and C. P. Huber, Tetrahedron, 1981, Supplement
No. 9, 117.
J. W. ApSimon, D. Moir, and K. Yamasaki, Can. J . Chem., 1981, 59, 1010.
J. M. Coisne, J. Pecher, J. P. Declercq, G. Germain, and M. Van Meerssche, Bull. SOC.Chim.
Belg., 1980, 89, 551.
0.D. Hensens, K. G. Lewis, and D. J. Tucker, Aust. J . Chem., 1980, 33, 2517.
A. Goswami and H. N. Khastgir, Indian J . Chem., Sect. B, 1980, 19, 315.
Triterpenoids
229
(157) R1= H,P-OH, R2= H,

(158) R' = 0, RZ = H,a-OH
(159) R1= H,P-OH, R2 0
1
09
(165) 13,18-ene
(166) 12,13-ene, 18a-H
The selective oxidation of oleanane triterpenoids by a Cr0,-py-BunOH-H,Oderived reagent has been studied.llgSome reactions of glycyrrhetic acid have been
llQ
Y.Kobayashi, M. Ogawa, and Y. Ogihara, J. Chem. SOC.,Perkin Trans. I , 1981, 2277.
230
des~ribed.l~O-l~~
Reaction of 16-oxofriedel-3-ene with zinc chloride in acetic acid
affords the rearranged products (164) and (165) in addition to the previously
described (1 66).124The enol acetylation of friedel-3-en-2-one has been
Rearrangements of friedelaneslZsand of the epoxide (1 67) have been studied.12'
The lH 128 and 13ClZ9 n.m.r. spectra of some friedelanes have been assigned,
olean-18-enes,131 hederas have the 13C n.m.r. spectra of some 0lean-l2-enes,1~~
agenin g l y c o ~ i d e sand
, ~ ~taraxeranes.
~
94 The mass spectra of some bryonolic acid
derivatives133and some f r i e d e l a n e ~have
l ~ ~ been discussed.
7 Ursane Group
New natural products include ursonic aldehyde (3-oxours- 12-en-28-al) from
Dragon's Blood, a resin from Daemonorops draco (Palmae),135dulcioic acid (168)
from Scoparia dulcis (Scr~phulariaceae),~~~
rubifolic acid (169) from Rubia cordifolia (Rubiaceae),13' esculentic acid (2a,3a,23-trihydroxyurs-12-en-28-oic
acid)
(168) R1= C02H, R2 = Me

(169) R' = CH20H, R2 = C02H
12*
121
lZ3
124
lZ5
126
lZ7
128
lZ9
130
131
132
133
13*
135
136
137
H.-0. Kim, M. P. Irismetov, R. Kh. Garyanov, M. I. Goryaev, and Kh. A. Alibaeva, Zzv. &ad.
Nauk Kaz. SSR, Ser. Khim., 1980, 61.
H.-8. Kim, R. Kh. Garyanov, M . P. Irismetov, and M. I. Goryaev, Izv. Akad. Nauk Kaz.
SSR, Ser. Khim., 1980, 85.
M. Kanaoka, S. Yano, H. Kato, and N. Nakano, Chem. Pharm. Bull., 1981, 29, 1533.
K. Takahashi, S. Shibata, S. Yano, M. Harada, H. Saito, Y. Tamura, and A. Kumagai, Chern.
Pharm. Bull., 1980, 28, 3449.
T. Kikuchi, M. Niwa, M. Takayama, T. Yokoi, and T. Shingu, Chern. Pharm. Bull., 1980, 28,
1999.
Y. P. Gupta and J. L. Courtney, Indian J . Chem , Sect. B, 1981, 20, 65.
A. S. R. Anjaneyulu and M. N. Rao, Indian J . Chern., Sect. B, 1980, 19, 634,
P. Sengupta, M. Sen, and S. N. Maiti, J . Indian Chem. SOC.,1980, 57, 1181.
T. Kikuchi, T. Yokoi, M. Niwa, and T. Shingu, Chem. Pharm. Bull., 1980, 28, 2014.
A. A. L. Gunatilaka, N. P. D. Nanayakkara, M. U. S. Sultanbawa, and M. I. M . Wazeer,
Org. Magn. Reson., 1980, 14, 415.
A. Patra, A. K. Mitra, S. Ghosh, A. Ghosh, and A. K. Barua, Org. Magn. Reson., 1981, 15,
399.
A. G. Gonzalez, B. M. Fraga, P. Gonzalez, M. G. Hernandez, and A. G. Ravelo, Phytochemistry, 1981, 20, 1919.
A. I. Kalinovskii and N . 1. Chetyrina, Khirn. Prir. Soedin., 1980, 359; English translation,
Chem. Nut. Compounds, 1980, 16, 269.
A. G . Panosyan, G . M. Avetisyan, V . A. Mnatsakanyan, and B. V. Rozynov, Bioorg. Khim.,
1980, 6 , 1094.
J. Schmidt, S. Huneck, and W. Ihn, J . Prakt. Chem., 1980, 322, 695.
G . Nasini and F. Piozzi, Phytochemistry, 1981, 20, 514.
S. B. Mahato, M . C . Das, and N. P. Sahu, Phytochemistry, 1981, 20, 171.
S. K. Talapatra, A. C. Sarkar, and B. Talapatra, Phytochemistry, 1981, 20, 1923.
Triterpenoids
23 1
(172) R1 = Ac, R2= H

(173) R1 = H,R2 = AC
from the fern DipZazium esculentum (Athyriaceae),13*polemoniogenin ( 1 70) from
PoZemonium coeruZeum (Polemonia~eae),1~~
a lactone, probably (1 71), from Pieris
japonica (Ericaceae),lQ0and the acetates (1 72) and (1 73) from Myrianthus arboreus
(Urti~aceae).~~~
Degradation of ursolic acid gave the triester (174) which was required to correlate
the stereochemistry of a key intermediate in the synthesis of (-)-(S)-2-hydroxyP-ionone.142 Rearrangement of the epoxide (1 75) has been
Fe @
C0,Me
AcO
AcO
( 174)
(175)
The 13C n.m.r. spectra of some urs-12-enes130 and the mass spectra of 18x,19pH-ursane ring E lactoneslQ4have been reported.
8 Hopane Group
3P-Hydroxy-17-methylhopane(1 76) and 29-hydroxy-3,17-dimethylhopane(1 77)

have been isolated from the photosynthetic bacterium Rhodomicrobium vannielii.
The origin of the 3P-oxygen atom of (176) poses an interesting biogenetic question
since the bacterium was grown under strictly anaerobic conditions.145Examination
of some recent sediments has shown the presence of unaltered bacteriohopanoids
138
13$
140
141
142
143
144
145
R. Tandon, G. K. Jain, R. Pal, and N. M. Khanna, Indian J . Chem., Sect. B, 1980, 19, 819.
R. Tandon, G. K. Jain, R. Pal, and N. M. Khanna, Indian J . Chem., Sect. B. 1981. 20. 46
M. Katai, T. Terai, and H. Meguri, Chem. Pharm. Bull., 1981, 29,261.
C. M. Ojinnaka, J. I. Okogun, and D. A. Okorie, Phytochemistry, 1980, 19, 2482.
S. Escher, W. Giersch, and G. Ohloff, Helv. Chim. A d a , 1981, 64, 943.
A. K. Sil, J. K. Ganguly, K. P. Dhara, C. P. Dutta, and D. N. Roy, IndianJ. Chem., Sect. B,
1981, 20, 201.
J. Protiva, E. Klinotova, H. Skorkovska, and A. Vystrcil, Collect. Czech. Chem. Commun.,
1981, 46, 1023.
D. L. Howard and D. J. Chapman, J . Chem. Soc., Chem. Commun., 1981, 468.
232
( 180)
such as diploptene (1) together with many modified hopanoids typical of sedimentary rocks. This supports the hypothesis that the former are precursors of the
latter.146 The trisnormoretane (1 78) is the major saturated hydrocarbon of a
The structure of thysanolactone (179), a novel ring A seco moreJurassic
tane from Thysanospermum dzflusum (Rubiaceae) was established by X-ray
analysis.148The X-ray crystal and molecular structure of 9(11)-fernene (180) has
been r e ~ 0 r t e d . l ~ ~
9 Miscellaneous
The stereochemistries of the three isomeric onoceranediol diacetates have been
assigned.150Wightianol-A ( 1 8 I ) and -B (1 82) from Lycapodium wightianum (Lycopodiaceae)151 and 3a-hydroxy- 14-serraten-21-one (1 83)152 and the novel norserratene (1 84)153from Pinus monticola (Pinaceae) are new natural products. The
lA6
M . Rohmer, M . Dastillung, and G. Ourisson, Naturwissenschaften, 1980, 67, 456; see also.
R. C. Barrick and J . I. Hedges, Geochim. Cosmochitn. Acta, 1981, 45, 381.

147
148
149
IS0
151
lS2
153
M. Bjoroy and J. Rullkotter, Chem. Geol., 1980, 30, 27.

N. Aimi, K. Yamaguchi, M . Takahashi, M . Iwata, S. Sakai, J. Haginiwa, and Y.Iitaka,
Tetrahedron, 1981, 37, 983.
H. W. Schmalle, 0. H. Jarchow, and B. M . Hausen, Acta Crystalfogr., Sect. B, 1980, 36, 2450.
Y. Tsuda and T. Sano, Chem. Pharm. Bull., 1980,28, 3134.
Y. Tsuda, Y. Tabata, and Y . Ichinohe, Chem. Pharm. Bull., 1980, 28, 3275.
A. H. Conner, B. A. Nagasampagi, and J. W. Rowe, Phytochemistry, 1980, 19, 1121.
A. H. Conner, T. P. Haromy, and M . Sundaralingam, J . Org. Chem., 1981, 46, 2987.
233
Triterpenoids
OH
(181) 14,15-dihydro,14P-OH
(1 82)
fl-(cH2
0 .
(185)
(186)
(187)
R
R
=0
= H,P-OAc
234
rearrangement of 3$,4p-epoxyshionane (1 85) has been

The sponge
Jaspis stellifera is a novel source of the malabaricane type triterpenoids (186)(1 88).155 Another sponge, Siphonochalina siphonella, contains sipholenol (1 89),
whose structure was established by X-ray analysis of the derived 4-acetate. The
name sipholane has been proposed for this new squalene-derived ~ k e 1 e t o n . l ~ ~
Terretonin (see Vol. 11, p. 132) has been shown to be of mixed polyketideterpenoid origin .15
10 Triterpenoid Saponins
The interesting biological properties shown by many saponins, coupled with

improvements in spectroscopic methods of structure determination have led to
the increased study of this class of compound. The following papers deal with
saponins and prosapogenins which are based on known triterpenoids of the following groups : d a m m a r a n e - e ~ p h a n e ,l ~~~p~a n e ,o1eanane,l6O
l~~
and ursane.lG1
Desorption/chemical ionization mass spectrometry is a useful technique for the
investigation of underivatized polar and involatile compounds such as triterpenoid
saponins.162The cleavage of saponins by anodic oxidation has been investigated,163
as has the glycosidation of triterpenoids.164
L. Cattel, L. Delprino, and A. Dietsch, Gazz. Chim. Ital., 1979, 109, 705.
B. N. Ravi, R. J. Wells, and K. D. Croft, J . Urg. Chem., 1981, 46, 1998.
156 U. Shmueli, S . Carmely, A. Groweiss, and Y. Kashman, Tetrahedron Lett., 1981, 22, 709.
15' C. R. McIntyre and T. J. Simpson, J . Chem. Soc., Chem. Commun., 1981, 1043.
15* Y. Kimura, Y. Kobayashi, T. Takeda, and Y . Ogihara, J . Chem. Soc., Perkin Trans. I , 1981,
1923; M. Ikram, Y. Ogihara, and K. Yamasaki, J . Nar. Prod., 1981,44,91; M. Okano, K.-H.
Lee, I. H . Hall, and F. E. Boettner, ibid., p. 470; S . E. Chen, E. J . Staba, S. Taniyasu, R. Kasai,
and 0. Tanaka, Planta Med., 1981, 42, 406.
15B P. K. Minocha and K. P. Tiwari, Phytochernistry, 1981, 20, 135; D. Mandloi and P. G. Sant,
ibid., p. 1687.
H. Ishii, M. Nakamura, S.,Seo, K. Tori, T. Tozyo, and Y. Yoshimura, Chem. Pharm. Bull.,
1980, 28, 2367; H. Kizu and T. Tomimori, ibid., pp. 2827, 3555; T. Konoshima, H. Inui, K.
Sato, M. Yonezawa, and T. Sawada, ibid., p. 3473; S. Takabe, T. Takeda, Y. Ogihara, and
K. Yamasaki, J . Chem. Res. ( S ) , 1981, 16; H. Ishii, K. Tori, T. Tozyo, and Y. Yoshimura, J .
Chem. Soc., Perkin Trans. I , 1981, 1928; P. N . Singh and S . B. Singh, Phyrochemistry, 1980,
19, 2056; R. D. Tripathi and K. P. Tiwari, ibid., p. 2163; T. Konoshima, H. Fukushima, H.
Inui, K. Sato, and T. Sawada, ibid., 1981, 20, 139; M. Moreno and V. M. Rodriguez, ibid.,
p. 1446; M. Masood, P. K. Minocha, K. P. Tiwari, and K. C. Srivastava, ibid., p. 1675; T.
Aoki, K. Shido, Y . Takahashi, and T. Suga, ibid., p. 1681; P. Forgacs and J. Provost, ibid.,
p. 1689; R. Encarnacion, L. Kenne, G . Samuelsson, and F. Sandberg, ibid.. p. 1939; Y. Okada,
K. Koyama, K. Takahashi, T. Okuyama, and S. Shibata, Planta Med., 1980,40,185; S . Ghosal,
A. K. Srivastava, R. S . Srivastava, S. Chattopadhyay, and M. Maitra, ibid., 1981, 42, 279;
H. Ishii, I. Kitagawa, K. Matsushita, K. Shirakawa, K. Tori, T. Tozyo, M. Yoshikawa, and
Y. Yoshimura, Tetrahedron Lett., 1981, 22, 1529.
P. K. Minocha and R. N. Tandon, Phytochemistry, 1980, 19, 2053.
162 K. Hostettmann, J. Doumas, and M. Hardy, Helv. Chim. Acta, 1981, 64, 297.
163 I. Kitagawa, T. Kamigauchi, H. Ohmori, and M. Yoshikawa, Chem. Pharm. Bull., 1980, 28,
3078.
164 A. A. Akimaliev, N. Sh. Pal'yants, P. K. Alimbaeva, and N. K. Abubakirov, Khim. Prir.
Soedin., 1979, 668; W. Janiszowska, B. Wilkomirski, and Z. Kasprzyk, Pol. J . Chem., 1980,
54, 2147; see also ref. 50.
l5*
155
5
Carotenoids and Polyterpenoids
BY G.BRITTON
1 Carotenoids
Introduction.-This Report covers the literature published up to approximately the
end of September, 1981. Few new carotenoid structures have been reported. The
main advances in carotenoid chemistry have been in the stereospecific synthesis of
carotenoids with chiral end-groups. Current interest in the possible use of retinoids
in cancer chemotherapy has prompted the preparation of a considerable number of
retinoic acid analogues. There has been no major new development in the use of
physical methods but h.p.1.c. becomes more and more the method of choice for
carotenoid separation, purification, and assay, and the increasing number of
papers on resonance Raman spectroscopy emphasizes the potential value of this
technique in the carotenoid field.
Reviews.-The major new publication is Volume 1 of the completely rewritten
second edition of Goodwin's book1 'The Biochemistry of the Carotenoids'. This
volume gives an introduction to carotenoid chemistry and a comprehensive survey
of the distribution, biosynthesis, and functions of carotenoids in plants and microorganisms. The biochemistry of plant carotenoids is also dealt with in an extensive
review by Spurgeon and Porter.2 The second edition of Czygan's book3 'Pigments
in Plants' includes chapters on carotenoid bio~ynthesis,~"
xanthophyll interconversion^,^^ photoregulation of carotenoid bio~ynthesis,~"
and carotenoids in
algal c h e r n o t a ~ o n o m yElsewhere,
.~~
reviews have been published on the use of
carotenoids as food c o l o u r ~ , the
* ~ ~metabolic and nutritional significance of carotenoids,6 carotenoids in green and purple photosynthetic bacteria, and carotenoid
biosynthesis in plants, especially enzymic aspects.a The retinoid field is surveyed in
T. W. Goodwin, 'The Biochemistry of the Carotenoids', Vol. 1, 2nd Edn., Chapman and Hall,
London, 1980,432 pp.
S. L. Spurgeon and J. W. Porter, in 'Biochemistry of Plants,' ed. P. K. Stumpf, Academic Press,
New York, 1980, Vol. 4, p. 419.
'Pigments in Plants', 2nd Edn., ed. F.-C. Czygan, Gustav Fischer, Stuttgart and New York,
1980; (a) B. H. Davies, p. 31; (b) A. Hager, p. 57; (c) W. Rau, p. 80; (d) A. Weber and M.
Wettern, p. 104.
J. N. Counsell, Dev. Food Colours, 1980, 1, 151.
H. Klaui, in 'Natural Colours in Food and other Uses, International Symposium 1979', ed.
J. N. Counsell, Applied Science Publishers, London, 1981, p. 91.
K. L. Simpson and C. 0. Chichester, Ann. Rev. Nutrition, 1981, 1, 351.
T. W. Goodwin, J. Sci. lad. Res., 1980, 39, 682.
J. W. Porter, S. L. Spurgeon, and D. Pan, Dev. Plant Biol., 1980, 6, 321.
235
236
two extensive b o o k ~ , ~
and
J ~two collections of Symposium proceedings deal with
light-energy transduction mechanisms in visual cellsll and HaIohacterium halobium12
respectively.
New Structures and Stere0chemistry.-Carotenoids. Of the few new carotenoid
structures that have been reported, all but one are from marine animals. Lactucaxanthin, a major xanthophyll in chloroplasts of lettuce (Lactuca saliva) and
OH
&--,
-=.
(1) R1 = R2 = a
(2) R1 = b, R2 = c
(3) R1= d, R2 = c
(4) R1= e, R2 = f
( 5 ) R1 = g, R2 = h
(6) R1 = c, R2 = i
(7) R1 = R2 = j
(8) R1 = R2 = d
(9) R1 = d, R2 = k
(10) R1 = R2 = k
(11) R1 = k, Ra = i
Retinoids : Advances in Basic Research and Therapy, ed.-C. E. Orfanos, 0. Braun-Falco,

E. M. Farber, C. Grupper, M. K. Polano, and R. Schuppli, Springer, Berlin, 1981, 527 pp.
lo Modulation of Cellular Interactions by Vitamin A and Derivatives (Retinoids), ed. L. M.
DeLuca and S. S. Shapiro, N. Y. Acad. Sci., 1981,430 pp (also published as Ann. N.Y. Acad.
Sci., Vol. 359).
l1 Phofochem. Photobiol, 1980,32, 423.
Photochem. Photobiol, 1981,33,417.
@
237
related species, has been identified13by n.m.r. and c.d. correlation as (3R,6R,3R,
hR)-~,~-carotene-3,3-diol
(I), the sixth of the ten possible chiral isomers of this
diol to be found in Nature. 78-Didehydro-p,p-carotene-3,4,3-triol
(2) has been
obtained from a number of she1lfish.l4-l6The structure was confirmed by NaBH,
reduction of pectenolone (3,3-dihydroxy-7,8-didehydro-p,p-caroten-4-one
(3).
The 3,4-cis-vic-diol thus formed was identical to the new carotenoid. Three new
pigments from the sponge Microciona prolifera have been characterized by their
spectroscopic properties1 as 3,4(or 2,3)-didehydro-y,~-carotene
(4),3-hydroxy-x,~carotene-6,8-dione [trikentriophidin (5)], and 7,8-didehydro-p,p-caroten-3-01
[allobetaxanthin (6)]. The occurrence of free actinioerythrol [3,3-dihydroxy-2,
2-dinor-p,p-carotene-4,4-dione
(7)] and its monoester in the sea anemones
Actinia equina and A . tenebrosa has been reported for the first time.18 The fatty
acid composition of the (7) diester, actinioerythrin, the main pigment of these
animals, has been describedlg along with those of astaxanthin [3,3-dihydroxy-p,
p-carotene-4,4-dione (S)] esters from Haematococcus pluvialis and Panadalus
borealis. The preparation of ( -)-camphanate diesters followed by h.p.1.c. separation is a good method for determining the isomeric composition of samples of (8)
and adonirubin [3-hydroxy-p,p-carotene-4,4-dione (9)].20The astaxanthin of the
shrimp Pandalus borealis21and of salmon22contained the (3R,3R)-, (3R,3S)-, and
(3S,3S)-isomers. The absolute configuration of mimulaxanthin [6,7,6,7-tetradehydro-5,6,5,6-tetrahydro-p,p-carotene-3,5,35-tetrol
(12)] from Lamium montanum has been determined23 as (3S,SR,sR,3S,SR,6R) by degradation and
R2
(12) R1 = R2 = a (X = H)
(13) R1 = a (X = H), R2 = b (Y = CH=CH)
(14) R1= a (X = H), R2= c
(15) R1= a (X = Ac), R2= b (Y = CH2CO)
D. Siefermann-Harms, S. Hertzberg, G. Borch, and S . Liaaen-Jensen, Phytochemistry, 1981,
20, 85.
l4 T. Matsuno, T. Maoka, and K. Hiraoka, Bull. Jpn. SOC.
Sci. Fisheries, 1981,47, 143.
16 T.Matsuno and T. Maoka, Bull. Jpn. SOC.Sci. Fisheries, 1981,47, 377, 495.
l8 T. Matsuno, K. Hiraoka, and T. Maoka, Bull. Jpn. SOC.Sci. Fisheries, 1981,47, 385, 501.
C. Litchfield and S . Liaaen-Jensen, Comp. Biochem. Physiol., 1980,6 W ,359.
J. D. Tauber, A. Fiksdahl, and S. Liaaen-Jensen, Biochem. Syst. Ecol., 1980,8,437.
l 8 B. Renstrcam and S. Liaaen-Jensen, Comp. Biochem. Physiol., 1981,69B,625.
8o R. K. Muller, K. Bernhard, H. Mayer, A. Ruttimann, and M. Vecchi, Helv. Chim. Acta, 1980,
63,1654.
*l B. Renstrram, G. Borch, and S. Liaaen-Jensen, Comp. Biochem. Physiol., 1981,69B,621.
88 K.Schiedt, F. J. Leuenberger, and M. Vecchi, Helv. Chim. Acta, 1981,64, 449.
R. Buchecker and C. H. Eugster, Helv. Chim. Acta, 1980,63,2531.
la
238
spectroscopic and c.d. comparison with neoxanthin [(3S,SR,SR,3S,SR,6S)-5,

6-epoxy-6,7-didehydro-5,6,5,6-tetrahydro-p,
p-carotene-3,5,3-triol (1 3)]. Similarly, desepoxyneoxanthin has been shown to be (3S,5R,6R,3R)-6,7-didehydro-5,
6-dihydro-p,p-carotene-3,5,3-triol
(14). For these correlations, the difficult
desepoxidation of neoxanthin was achieved with BuLi-FeC1, after silylation.
Chiroptical correlation of its hexa-acetate with (2S,2S)-bacterioruberin [2,2-bis(3-hydroxy-3-methylbutyl)-3,4,3,4-tetradehydo1,2,12-tetrahydro-+,+-carotene1,
1-diol (1 6)] and plectaniaxanthin [3,4-didehydro-1,2-dihydro-p,+-carotene1 ,
2-diol ( 17)] p-D-glucoside supported the assignment of the (2R,2R)configuration
for oscillaxanthin [ 1,2,12-tetrahydro-+,+-carotene1,2,1,2-tetrol 2,2-rhamnoside
(1 S)].24
OH
(16) R1= R2= a

R1= b, R2= c (X = H)
(18) R1= R2= c (X = rhamnosyl)
(17)
New NaturalProducts Related to Carotenoids. New compounds which have norcarotenoid-like structures include ambliol A (19), dehydroambliol A (20), and ambliolide
(21), diterpenoids from the sponge Dysidea a m b l i ~ deoxyabscisic
,~~
acid (22), a
precursor to abscisic acid (23) in Cercospora rosicolaYz6and two tobacco products,
3-hydroxy-5,6-epoxy-p-ionyl-~-~-glucopyranoside
(24)27 and 8,9-dihydroxy-8,9dihydromegastigmatrienone (25).28 The absolute configuration of (-)-(S)-2hydroxy-p-ionone (26) has been determined by correlation with ursolic acid and
( -)-trans-verbenol. 29
Carotenoid-Protein Complexes. Three new purple-blue carotenoprotein complexes
from invertebrate animals have been described. That from the carapace of
Orconectes Iimosus (Amax 335, 460, 675 nm) has astaxanthin (8) and canthaxanthin
and that from the fly Rhyn[p,p-carotene-4,4-dione(lo)] as prosthetic
chosciara americana (Amax 465,545 nm) has one canthaxanthin and one echinenone
[p,p-caroten-4-one (1 l)] per mole of protein.31 The sponge Suberites domuncula
H. Ranneberg, P. FOSS,
T. Ramdahl, G. Borch, 0. M. Skulberg, and S. Liaaen-Jensen, Phyrochemistry, 1980, 19, 2167.
25 R. P. Walker and D. J. Faulkner, J . Urg. Chem., 1981, 46, 1098.
28 S. J. Neill, R. Horgan, T. S. Lee, and D. C. Walton, FEBS Lett., 1981, 128, 30.
2 7 H. Kodama, T. Fujimori, and K. Kato, Agric. Biol. Chem., 1981, 45, 941.
2 8 Y . Takagi, T, Fujimori, H. Kaneko, and K. Kato, Agric. Biol. Chem., 1981,45, 787.
2 g S . Escher, W. Giersch, and G. Ohloff, Helv. Chim. Acta, 1981, 64, 943.
30 B. Czeczuga and S. Krywuta, Comp. Biochem. Physiol., 1981, 68B, 339.
31 W. R. Terra, C. Ferreira, A. G. De Bianchi, and K. Zinner, Comp. Biochem. Physiol., 1981,
68B, 89.
Z4
239
6.X
b*
Me
OH
(19) X = a-Me, P-OH

(20) X = CH2
OMe
(21)
-Glucose
0W
(22) X
(23) X
HO
=H
= OH
(24)
yielded a blue carotenoprotein (31 000 dalton) in which the carotenoid was not
identified but described as similar to a monohydroxymonoepoxycarotene.32A new
fucoxanthin [5,6-epoxy-3,3,5-trihydroxy-6,7-didehydro-5,6,7,8,5,6-hexahydroP,P-caroten-8-one 3-acetate (1 5)]-chlorophyll a-protein complex from brown algae
and diatoms has been described.33
Synthesis and Reactions.-Curotenoids. Two review a r t i c l e ~ ~devoted

* - ~ ~ to synthetic methods in the isoprenoid field contain information that is, or may be, useful
for carotenoid synthesis. Methods have been reported for the synthesis of a
..OH
HO
w c M e 2 O M e x&H20H
Y
(28)
(31) X
(32) X
= OH,
3 Br-
(29) X =OH, Y = H
(30) X = H, Y = OH
= H,
Y =H
Y = OH
L. Cariello and L. Zanetti, Mar. Biol. (Berlin), 1981, 62, 151.

33
R. S. Alberte, A. L. Friedman, D: L. Gustafson, M. S. Rudnick, and H. Lyman, Biochim.
36
Biophys. Acta, 1981, 635, 304

M. Julia, in Organic Synthesis Today and Tomorrow, Proc.IUPAC Symp. Org. Synth., 3rd
1980, ed. B. M. Trost and C. R. Hutchinson, Pergamon, Oxford, 1981, p. 231.
G. Cainelli and G. Cardillo, Acc. Chem. Res., 1981, 14, 89.
240
(33)
(34)
number of carotenoids with chiral end-groups. The (3R,3R)-, (3S,3S)-, and

(3R,3S, meso)-isomers of zeaxanthin [P, P-carotene-3,3-diol (27)] have been
prepared by a route which utilizes asymmetric hydroboration as the key reaction.36
Thus safranol isopropenylmethyl ether (28), on hydroboration with ( +)- or
(-)-di-isopinocamphenylborane gave the optically pure (R)-and (S)-diols (29)
and (30) respectively. Chain elongation and conversion into the C15 Wittig salts
(31) and (32) followed by reaction with the appropriate aldehyde (33) or (34)
afforded the (27) isomers. The synthesis of (3R,3R,6R)-lutein [P,~-carotene-3,3diol (35)] was achieved from (R)-4-hydroxy-2,6,6-trimethylcyclohex-2-en1-one
(36) as a readily available key intermediate.37 This was used to prepare the C,,
&
HO
p
i
c1-+
HO
Wittig salt (37) for reaction with (34) to give lutein. The synthesis of all-trans(3S,3S)-7,8,7,8-tetradehydroastaxanthin [3,3-dihydroxy-7,8,7,8-tetradehydrop, p-carotene-4,4-dione (3S)] and all-trans-(3S,3S)-7,8-didehydroastaxanthn[3,3dihydroxy-7,8-didehydro-P,p-carotene-4,4-dione
(39)], the two components of
asterinic acid, and of their 9-cis- and 9,9-di-cis-isomers from (4S)-(2E)-5-(4hydroxy-2,6,6-trimethy1-3-oxocyclohex1-eny1)-3-methylpent-2-en-4-ynal(40)
as
starting material in a CI5 + C,, + C15Wittig scheme.38The (3R,3R)-, (3S,3S)-,
and (3R,3S)-isomers of astaxanthin (8) can be obtained from a synthetic racemate
by separation of the diastereomeric di-( -)-~amphanates.~~
The preparation of
(3R)+-citraurin [3-hydroxy-8-apo-P-caroten-8-al
(41)], (3R)-P-citraurol [8-apoP-carotene-3,8-diol (42)], and (3R)-p-citraurinene [8-apo-P-caroten-3-01 (43)]
from the C,, Wittig salt (31) has been reported.40
36
37
38
38
A. Riittimann and H. Mayer, Helv. Chim. Acta, 1980, 63,1456,
H.Mayer and A. Ruttimann, Helv. Chim. Acta, 1980, 63,1451.

K.Bernhard, F. Kienzle, H. Mayer, and R. K. Muller, Helv. Chim. Acta, 1980, 63,1473.
R.K. Muller, K. Bernhard, H. Mayer, A. Riittimann, and M. Vecchi, Helv. Chim. Acta, 1980,
63, 1654.
H.Pfander, A. Lachenmeier, and M. Hadorn, Helv. Chim. Acta, 1980, 63,1377.
24 1
(38) X = Y = C E C
(39) X = C E C , Y = CH=CH
HO
(41) R = CHO
(42) R = CH20H
(43) R = Me
0
(4.0)
Tedanin [P,~-carotene-3,4-dione (44)], tethyatene [3,4-didehydro-(3 ,X-carotene

(45)], and agelaxanthin A [PYcp-caroten-3-ol(46)] have been prepared from (41)
acetate.41MnOz oxidation of (45) gave renieratene [cp,X-carotene (47)] in low yield.
0
a
(44) R1= a, R2 = b
(45) R1= C, R2= b
(46) R1= d, R2= e

(47) R1= e, R2= b
Further syntheses of zeaxanthin (27) and rhodoxanthin [4,5-didehydro-4,5retro-p,p-carotene-3,3dione(48)] have been described.42In a simplification of a
previous procedure, the acetylenic trio1 (49) was reduced (LiAlH,) to the allenic
diol (50), which with PPh,Br underwent rearrangement to the 3-hydroxy-p-ring
41
A. Shimada, Y. Ezaki, J. Inanaga, T. Katsuki, and M. Yamaguchi, Tetrahedron Lett., 1981,22,

773.
P. R. Ellis, A. E. Faruk, G . P. Moss, and B. C. L. Weedon, Helv. Chim. Acta, 1981, 64, 1092.
242
Wittig salt (51). Wittig reaction with the C,, dialdehyde (52) gave racemic (27).
The 3-hydroxy-p-ring system was also obtained from a-ionone (53). Oxidation
with t-butyl chromate gave the ketone (54), which with ethanediol underwent
double-bond migration to give (55), which was hydrolysed in the presence of
(53)
(54)
cyanoborohydride to the intermediate (56) en route to (27). 3-Keto-cx-ionone (57)

gave the diacetal (58), mild hydrolysis of which afforded (59), the key intermediate
in a synthesis of (48). The C,, epoxy Wittig salt (60) has been used to synthesize
lycopene 1 ,Zepoxide [lY2-epoxy-1,2-dihydro-#,#-carotene(61)] and 1,2 :1,2-
(57)
243
(62)],43 and the

diepoxide [ 1,2:1,2-diepoxy-I,2,1,2-tetrahydro-~,+-~arotene
1,2-epoxides of y- and %carotenes [ 1,2-epoxy-1 ,2-dihydro-p,$-carotene(63)
(61)
(62)
(63)
(64)
(65)
R1= a, R2= b
R1= R2= a
R1= c, R2= a
R1 = d, R2= a
R1= e, R2= b
(66)
(67)
(68)
(69)
(70)
R1= R2= e
R3= f, R2= b
R1= R2= f
R1= R2= g
R1= R2= h
(71)
(72)
(73)
(74)
(75)
R1= R2= i
R1= R2= j
R = R2= k
R1= R2= 1
R1= R2= c
and 1,2-epoxy-l,2-dihydro-~,$-carotene
(64)].44The acetonides (65) and (66) of
the 1,2-diol(67) and 1,2,1,2-tetrol (68) were also prepared.43Synthetic carotenoid
analogues with 2- and 3-pyridyl, 2- and 3-furyl, and 2- and 3-thienyl end-groups,
(69)-(74), have been made from the corresponding Wittig salts and the C,,
crocetindial (76).45 A novel carotenoporphyrin ester (77) has been prepared and
used as a model in light-energy transfer s t ~ d i e s . ~An
~ - ~unusual
*
1,6-methano[lO]annulene homologue (78) of P-carotene [P,P-carotene (75)]has been synthesized
by a Wittig reaction between the retinol derivative (79) and the cyclic dialdehyde
Treatment of zeaxanthin (27) with chlorsulphonic acid followed by base
gave the disulphate salt (8 l).50 Lycoxanthin ($,$-caroten- 16-01) monosulphate (82)
43
44
45
H. Pfander, M. Kamber, and Y . Battegay-Nussbaumer, Helv. Chim. Acta, 1980, 63, 1367.
H.Pfander and M. Kamber, Helv. Chim. Acta, 1980, 63, 1792.

H.R. Brahmana, K. Katsuyama, J. Inanaga, T. Katsuki, and M. Yamaguchi, TetrahedronLett.,
1981,22, 1695.
46
47
48
4s
6o
G . Dirks, A. L. Moore, T. A. Moore, and D. Gust, Photochem. Photobiol., 1980, 32, 277.
A. L. Moore, G . Dirks, D. Gust, and T. A. Moore, Photochem. Photobiol., 1980, 32, 691.
R. V. Bensasson, E. J. Land, A. L. Moore, R. L. Crouch, G . Dirks, T. A. Moore, and D. Gust,
Nature, 1981, 290, 329.
R. Neidlein and H. Zeiner, Arch. Pharm. (Weinheim, Ger.), 1980, 313, 970.
T.Ramdahl and S. Liaaen-Jensen, Acta Chem. Scand., Ser. B, 1980, 34,773.
244
HO
0
d
(81) R1= R2 = a
(82) R1= b, R2= c
(83) R1= R2 = d
245

0
OH
(84)
HO
0
0
OH
HO
was prepared similarly. Epoxidation of astacene [3,3'-dihydrox~-2,3,2',3'-tetradehydro-@,@-carotene-4,4'-dione(83)] with perbenzoic acid gave the 9,lO-, 11,12and 9,12-epoxides (84)-(86).51 Astacene has been
to form complexes with
Al, Cr"', Cd*,
Fe'I', and Hg" salts, including a stable 1 : 1 complex with Fe(NO,),.
Cleavage of 8'-apo-p-carotenylidene oxazolone (87) with aqueous or methanolic
NaOH, piperidine, or morpholine gave the 7'-benzoylamino-@-apo-6'-carotenoic
acid derivatives (88) (R = OH, OMe, piperidinyl, or m o r p h ~ l i n o ) Mono.~~
and
di-anions of p-carotene have been formed by reaction with a Na mirror in THF.54
The oxidation of @-carotenewith nitroxyl radical compounds has been
The pyrolysis of p-carotene under various conditions afforded a range of methylbenzenes, methylnaphthalenes and p h e n a n t h r e n e ~ Kinetic
. ~ ~ ~ ~ studies
~
have been
reported of reactions of @-caroteneand retinyl acetate (89) with various radicals58
and with peroxide oxygen and dicyclohexyl peroxydicarb~nate.~~
61
6s
64
bb
66
b7
O8
D. Osianu, E. Nicoara, and C. Bodea, Rev. Roum. Chim., 1980, 25, 261.
J. Zsako and T. Laszlo, Rev. Roum. Chim., 1981, 26, 237.
V. Ciurdaru, V. Tamas, and K. L. Simpson, Rev. Roum. Chim., 1980, 25, 571.
G. N. Sinyakov, Zh. Prikl. Spektrosk., 1981, 35, 487.
0. T. Kasaikina, T. V. Lobanova, A. B. Gagarina, and N. M. Emanuel, Dokl. Akad. Nauk
SSSR, 1980, 255, 1407.
M. Ishiwatari, J. Anal. Appl. Pyrolysis, 1980, 2, 153.
M. Ishiwatari, J . Anal. Appl. Pyrolysis, 1981, 2, 339.
0. T. Kasaikina, Z. S. Kartasheva, and A. B. Gagarina, Zzv. Akad. N a u ~SSSR,Ser. Khim.,
1981, 536.
Z. S. Kartasheva, 0. T. Kasaikina, and A. B. Gagarina, Izv. Akad. Nauk SSSR, Ser. Khim.,
1981, 541.
246
NHCOPh
(87) X
NY
Ph
(88) X
'.*?
COR
(89) R = CH20Ac
(90) R = CHO
(91) R = CH20H
(92) R = C02H
Retinoids. The 9,ll-di-cis-isomer of retinaldehyde (90) has been prepared in six
steps from the C15 aldehyde (93) and used to form a 9,ll-di-cis-rhodopsin with
cattle opsin.60The 9,ll-di-cis-isomer was also one of four di-cis forms obtained
by irradiation of all-trans-retinaldehyde in acetonitrile.61The sterically hindered
7-cis- and 7,13-di-cis-isomers of vitamin A [retinol (91)] have been prepared via
the 7-cis photoisomerization product of the sulphone (94).62Several isotopically
labelled species of retinaldehyde and derivatives have been synthesized, including
11-cis-[18-2H3]retinaldehyde(95) and 11-cis-[19-2H,]retinaldehyde,63(96), the alltrans-, 9-cis-, 1 1-cis-, and 13-cis-isomers of [ 10-2Hl]-, [ 1l-2Hl]-, [ 12-2Hl]-, and
[l 1, 12-2H,]-retinaldehyde,64 all-trans-[ 13,14-14C2]- and [ 1 l-3H,]-retinoic acid
(92),65-67 trans-[11-3H,]-5,6-epoxyretinoic acid (97),66 and trans-[1 1-3Hl]retinyl
acetate (89).67
(93)
R'
6O
62
63
64
6B
13'
(94)
(95) R1= CD,, R2= CH,

CHO
(96) R1= CH,, R2 = CD,
(97)
A. Kini, H. Matsumoto, and R. S. H. Liu, Bioorg. Chem., 1980, 9, 406.

M. Denny, M. Chun, and R. S. H. Liu, Photochem. Phofobiol., 1981, 33, 267.
D. Miller, M. Tramell, A. Kini, and R. S. H. Liu, Tetrahedron Lett., 1981, 22, 409.
M. R. Fransen, I. Palings, J. Lugtenburg, P. A. A. Jansen, and G. W. T. Groenendijk, Recl.
Trav. Chim. Pays-Bas, 1980, 99, 384.
A. D. Broek and J. Lugtenburg, Recl. Trav. Chim. Pays-Bas, 1980,99, 363.
H. Kaegi, E. Chew, and P.-L. Chien, J . Labelled Compd. Radiopharm., 1980, 17, 745.
P.-L. Chien and B. Amin, J . Labelled Compd. Hadiopharm., 1980, 17, 759.
H. H. Kaegi and J. I. Degraw, J. Labelled Compd. Radiopharm., 1981, 18, 1099.
247
Many retinaldehyde, retinol, and retinoic acid derivatives and analogues have
been synthesized. The (3R)-3-hydroxy-derivatives (98), (99), and (100) were
prepared from the optically active C,, Wittig salt (3 1).689-Bromoretinaldehyde
(101 ; trans and 9-cis), 13-bromoretinaldehyde (102; trans and 11-cis), phenylretinaldehyde (103; trans and 9-cis), and p-dimethylarninophenylretinaldehyde
(104; trans) have been prepared and used to make bacteriorhodopsin analogue^.^^
5,6-Dihydroretinaldehyde(105) and its desmethyl analogue (106) also formed
(98) R = CH,OH
(99) R = CHO
(100) R = COzH
10
(103) R = H
(104) R=NMe,
(1 05)
(106)
bacteriorhodopsin analogues, 70 as did a number of synthetic arylretinaldehyde

derivatives containing 1-5 conjugated double bonds. 71 The synthetic vitamin A
analogues (107) (R = Ac, Me, or H) have been prepared from (108) by a Wittig
scheme,72The many retinoic analogues to have been synthesized include a range
of aromatic fluorine derivatives (109)-( 1 13),73the cyclopropane derivatives (114)
and (1 15),74 and the bicyclic compounds (1 16) (R = H or Et), (1 17) (R = CO,H
or OH), and (1 18) (R = C0,H or OH).75The cyclopentane retinoid (1 19), obtainable from retinoic acid, underwent thermal reactions to give bicyclic derivatives
( 120)-( 125).76
**
OS
H. Mayer and J. M. Santer, Helv. Cylim. Acta, 1980, 63, 1467.

M. G . Motto, M. SheJres, K. Tsujimoto, V. Balogh-Nair, and K. Nakanishi,J. Am. Chem. Soc.,
1980,102,7947.
70
71
72
73
74
76
B. Mao, R. Govindjee, T. G. Ebrey, M. Amaboldi, V. Balogh-Nair, K . Nakanishi, and R.

Crouch, Biochemistry, 1981, 20, 428.
A. M. Shkrob, A. V. Rodionov, and Y. A. Ovchinnikov, Bioorg. Khim., 1981, 7 , 1169.
I. M. Yakovleva, L. A. Vakulova, T. M. Filippova, A. R. Bekker, and G. I. Samokhvalov,
Zh. Org. Khim., 1980, 16, 2289.
K.-K. Chan, A. C. Specian, and B. A. Pawson, J . Med. Chem., 1981,24, 101.
M. I. Dawson, P. D . Hobbs, R.L. S. Chan, and W.-R. Chao, J . Med. Chem., 1981,24, 1214.
M. I. Dawson, P. D . Hobbs, R. L. S. Chan, W.-R. Chao, and V. A. Fung, J . Med. Chem.,
1981, 24, 583.
70
P. Loliger and H. Mayer, Helv. Chim. Acta, 1980, 63, 1604.
248
R3+R5
iP
(109)
(110)
(111)
(112)
(113)
R' = R2= R5= Me, R3 = OMe, R4= H

R1= Cl, R2= H, R3 = OMe, R4 = R5= Me
R1= C1, R2= R5= Me, R3 = OMe, R4= H
R1= R5= C1, R2= H, R3 = OMe, R4= Me
R' = R3 = R5= Me, R2= C1, R4 = H
249
(123) X = 0
(124) X = H,OH
(125)
A procedure for the preparation of 1-bromoacetylenes and conjugated enynes

has been used to make the retinaldehyde derivative (126). Retro-aldol reaction of
the retinylidenedimedone (127) with MeNH, gave all-trans-retinaldehyde in 90 %
yield.* Oxidation of (127) gave the 5,6- and 5,8-epoxides (128) and (130).79The
4-acetoxy-, 4-hydroxy-, and 4-keto-derivatives (131) (X = H,OH, H,OAc, and 0
respectively) and the seco-compound (1 33) were also prepared. Compounds (128),
(130; X = 0), and (131) underwent retro-aldol reaction to give the aldehydes
(128) R
(129) R
(132) R
77
78
H. J. Bestmann and H. Frey, Liebigs Ann. Chem., 1980, 2061.

N. Acton and A. Brossi, Helv. Chim. Ada, 1980, 63, 1396.
N. Acton and A. Brossi, Helv. Chim. Ada, 1980, 63, 1391.
CHO
CHO
250
Terpenoidr and Steroids
(129), (132), and (134). The synthesis of D-glucuronic acid conjugates of N(4hydroxypheny1)- and N-(2-hydroxyethyl)-retinamide (135) (X = p-C,H, or CH,
NH
/
0
(133) R
HO
(134) R
OH
CHO
(135)
CH2) from trans-retinoyl chloride has been reported.8o Retinyl phosphate (136)
has been prepareda1in 40-60 % yield from retinol and POCI,. Thermal sigmatropic
rearrangement of the allenic retinoids (138) (R = H or SiMe,CMe,) gave the
12,14-retroretinol compounds (139) as a mixture of geometrical isomers.82 The
preparation of a water-soluble retinaldehyde-dextran complex has been described.
Two-electron electrochemical reduction of N-retinylidene-n-butylamine(I 37) gave
the 5,6-dihydro-derivative.84
(136) R
(137) R
= CH20POgH2
=
CH=NBu"
(141)
(142)
A study of solvent effects on the photoisomerization of retinaldehyde and the

C&, aldehyde (140) and G8ketone (141) has been
The kinetics of
formation and decay of radical anions of all-trans-retinaldehyde and derivatives
B1
83
84
86
M. I. Dawson and P. D . Hobbs, Carbohydr. Res., 1980, 85, 121.

S. P. Poznyakov and A. A. Dmitrovskii, Biokhim. Metody, 1980, 70.
J. Sueiras and W. H. Okamura, J . Am. Chem. SOC.,1980,102, 6255.
J. Pitha, S. Zawadzki, F. Chytil, D. Lotan, and R. Lotan, J . Natl. Cancer Inst., 1980, 65, 101 1.
K. J. Stutts, L. A. Powell, and R. M. Wightman, J . Electrochem. Soc., 1981, 128, 1248.
V. Ramamurthy, M . Denny, and R. S . H. Liu, Tetrahedron Lett., 1981, 22, 2463.
25 1
have been studied.86 The mechanisni of electrodimerization of retinaldehyde has

been elucidated. Kinetic studies of liquid-phase oxidation of retinyl acetate and
retinoic acid have been d e s ~ r i b e d . ~Hydrophobic
~-~~
bond energies of 11-cisretinaldehyde and P-ionone (142) have been calculated.a1
Carotenoid-like Compounds. Synthetic procedures for construction of the rings of
ionones and other substances structurally related to carotenoids, and other procedures for the preparation and transformations of such compounds, may be useful
in the carotenoid field. Thus reaction between the phenyl sulphide (143) and the
ClJLSPh
+J-
S0,Ph
+M,,,
R
(143)
(1.44)
(1 46)
(145)
(147)
(148)
Grignard reagent (144) (R = H or Me) followed by oxidation gave the sulphone

(145) which with ally1 bromide afforded the acyclic C,, compound (146).Q2This
gave rise to P-ionone (142) or a- and p-irones (147) and (148), cyclization being
achieved with H,P04. p-Cyclogeranyl phenyl sulphide (149) has been prepared
(149) R = CH,SPh
(150) R = CHO
Ph*f%zAc
&Ho
\
from (151) by sequential cyclization, reaction with ClCO,Et, and photochemical

addition of PhSH.Q3Selenium-assisted cyclization of (152) over BF,-Et,O, SnCl,,
CF3C02H,or HC0,H gave the cyclic compound (153), which was used in the
B6
88
O1
93
N. V. Raghavan, P. K. Das, and K. Bobrowski, J . Am. Chem. Soc., 1981, 103,4569.

L. A. Powell and R. M. Wightman, J . Electroanal. Chem. Interfacial Electrochem., 1981, 117,
321.
E. I. Finkel'shtein, N. A. Mednikova, and E. I. Kozlov, Zh. Org. Khim., 1981, 17, 929.
E. I. Finkel'shtein, N. A. Mednikova, I. S. Panasenko, and E. I. Kozlov, Zh. Org. Khim.,
1981, 17, 933.
E. I. Finkel'shtein, Y. M. Rubchinskaya, and E. I. Kozlov, Zh. Org. Khim., 1981, 17, 936.
T. Kakitani, H. Kakitani, and S. Yomosa, Biophys. Struct. Mech., 1980, 7, 101.
T. Mandai, K. Nishikawa, H. Yamaguchi, M. Kawada, and J. Otera, Chem. Lett., 1981, 473.
K. Takabe, T. Yamada, and T. Katagiri, Chem. Znd. (London), 1980, 540.
252
t 157)
(158) R = H
(160)
(159) R = OH
preparation of safranal(154). 94 Cyclization of 2-geranylthiophen and its 5-carboxyderivative (155) (R = H or C02H)gave products including (156) and (157).95New
syntheses have been reported for p-damascone (158) from P-cyclocitral( 150)9sand
3-hydroxy-P-damascone (159) in four steps from the keto-ester (160).9 7 a-Ionone
(161) was the starting material in new syntheses of dihydroedulans (163) and
theaspiranes, e.g. (1 64),98 and of the theaspirones (165). gg (&)-(166) has been
.o
Me
(161) R = 0
(162) R = H,OH
m
(165) R = 0
(166) R = H,
(171)
84
95
O7
WH
(172)
T. Kametani, K. Suzuki, H. Kurobe, and H. Nemoto, Chem. Pharm. Bull., 1981, 29, 105.
A. V. Semenovskii and M. M. Emelyanov, Izv. Akad. Nauk SSSR, Ser. Khim., 1980, 2578.
R. Pellicciari, E. Sisani, and R. Fringuelli, Tetrahedran Lett., 1980, 21, 4039.
Y . Tsujino, M. Shibagaki, H. Matsushita, K. Kato, and H. Kaneko, Agric. Biol. Chem., 1981,
45, 1731.
H. Etoh, K. Ina, and M. Iguchi, Agric. B i d . Chem., 1980, 44, 2871.

W. M. B. Koenst, W. Appeldoorn, and H. Boelens, Synrh. Commun., 1980,10,899.
253
prepared from dihydro-a-ionol (167) by sequential electrochemical chlorination,

dehydrochlorination, and cyclization.looA five-step route to the vitispirane diastereomers (168) used dehydro-p-ionone (169).lo1Diastereomers of dihydrololiolide
(170) were obtained, along with the dehydration product (171) from the cyclohexanone (172),lo2An efficient three-step preparation of all-trans-p-ionylidene-
pN
(173)
(174) R
(175) R
= CH=CH
(176)
= CHO
OH
(180)
acetaldehyde (140) from p-ionone (142) via the nitrile (173) has been described.lo3
Mild acid dehydration of a-ionol (162) gave products including megastigma-4,
7(E),Ptriene (1 74), which was oxidized to the aldehyde (175).lo4Other natural
products with carotenoid-like rings for which syntheses have been reported
include Latiu luciferin ( 176)lo5and mokupalide (177)?05J06( +)-farnesiferol C
(178),107 trans-y-monocyclofarnesol (179),lo8and the glucoside picrocrocin (18O).lo9
S. Torii, K. Uneyama, T. Nakai, and T. Yasuda, Tetrahedron Lett., 1981, 22, 2291.
T.Kato and H. Kondo, Bull. Chem. Soc. Jpn., 1981, 54, 1573.
lo2 S. Shibata, H. Matsushita, K. Kato, H. Kaneko, M. Noguchi, M. Saburi, and S. Yoshikawa,
Agric. Biol. Chem., 1981, 45, 315.
lo3
R.W.Dugger and C. H. Heathcock, Synth. Commun., 1980,10, 509.
lo4
B.-H. Song, D.L. Davis, and C. M. Song, J . Agric. Food Chem., 1980, 28, 997.
lo6
F.W. Sum and L. Weiter, Tetrahedron,Suppl. 1981, 303.
lo6 M. Kobayashi and E. Negishi, J . Org. Chem., 1980, 45, 5223.
lo' T. Mukaiyama and N . Iwasawa, Chem. Lett., 1981, 29.
lo*
0. P.Vig, M. L. Sharma, N. Trehan, and N. K. Verma, IndianJ . Chern., Sect. B, 1980,19,450.
loo H. Mayer and J. M. Santer, Helv. Chim. A d a , 1980, 63, 1463.
loo
lol
254
The I , 1-didesmethyl analogue (1 8 1) of abscisic acid (23) has been prepared.l1 The
cis-trans photoisomerization of (23) has been studied.l1 A convenient procedure
has been developed for the catalytic hydrogenation of p-ionone (142) to the cis-5,6dihydroionone (182).l12 On treatment with Me2S+CH;, P-ionone gave the epoxide
(183), which with MgBr, afforded the aldehyde ( 1 84) without halohydrin formatio n .l13
The photochemical reactions of ionones and related compounds have been
studied extensively and in most cases large numbers of products have been characterized. Compounds whose behaviour on irradiation have been investigated include
@R
(188) R
(189) R
111
02Me
p
\
@d
OR
= H,
= CH,
(190) R = 0
(191) R = CH,
(192)
E. Nagano, T. Oritani, and K. Yamashita, Agric. Biol. Chem., 1980, 44, 2095.
D. E. Brabham and R. H. Biggs, Photochem. Photobiol., 1981, 34, 3 3 .
C. N. Filer, J. C. Pugliese, J. C. Morrison, and D. G . Ahern, Org. Prep. Proced, Znt., 1981,
13, 140.
113
M. Rosenberger, W. Jackson, and G . Saucy, Helv. Chim. Acta, 1980, 63, 1665.
255
(E)- and (2)-p-ionone and the bicyclic compound (185)>14(E)- and (Z)-a-i~none,~
(E)-p-ionone oxime ethyl ether (186)>16 the cyclopropane derivative (187);17 the
epoxy-esters(188)llSand (189),119and the epoxides (19Oy2O (192) (R = H or Ac),121
(191), and (193).122The catalytic hydrogenation of compounds including p-ionone
with K,[Co(CN),H] in aqueous solution with phase-transfer reagents has been
described.12, The mechanisms of hydrogenation of 13-ionong~~
and pseudoionone
(1 94)125have been studied.
Physical Methods.-Separation and Assay. A range of isomers of astaxanthin (8)
diacetate (9-cis, I3-cis, 15-cis, 9,9-di-cis, 9,13-di-cis, 9,13-di-cis, 13,13-di-cis,
13,15-di-cis), prepared by thermal and iodine-catalysed isomerization of rrans-(8)
have been separated by h.p.l.c.126A procedure has been developed for separation
of bean leaf etioplast pigments, including c a r ~ t e n o i d s ,by
~ ~h.p.1.c.
~
H.p.1.c.
separations of esters of all-trans-, 9-cis-, 11-cis-, and 1 3 - ~ i ~ - r e t i n o l , l ~and
*-~~~
determinations of retinol in
retinol and 13-cis-retinoic
and the
aromatic retinoid (195)13,in plasma have been described. A reversed-phaseion-pair
h.p.1.c. method has been used for analysis of plant hormones including abscisic
acid.ls4T.1.c. methods have been described for the separation of green plant135and
phyt~planktonl~~
carotenoids, and paper chromatography of chloroplast pigments
114
116
116
117
118
H. Cerfontain and J. A. J. Geenevasen, Tetrahedron, 1981, 37, 1571.

C. P.Visser and H. Cerfontain, Recl. Trav. Chim. Pays-Bas, 1981, 100, 153.
P.Baas, H. Cerfontain, and P. C. M. Van Noort, Tetrahedron, 1981, 37, 1583.
K.Ishii, H. R. Wolf, and 0. Jeger, Helv. Chim. Acta, 980, 63, 1520.
A. P. Alder, H. R. Wolf, and 0. Jeger, Helv. Chim. Acta, 1980, 63, 1833.
K. Murato, B. Frei, W. B. Schweizer, H. R. Wolf, and 0. Jeger, Helv. Chim. Acra, 1980, 63,
1856.
lZo
lal
K. Murato, H. R. Wolf, and 0. Jeger, Helv. Chim. Acta, 1980, 63, 2212.
N. Nakamura, W. B. Schweitzer, B. Frei, H. R. Wolf, and 0. Jeger, Helv. Chim. Acta, 1980,
63,2230.
12z
lZ3
lZ4
lZ5
126
lZ8
lZ0
132
133
la4
lS5
136
A. P. Alder, H. R. Wolf, and 0. Jeger, Helv. Chim. Acta, 1981, 64, 198.
D.L.Reger, M. M. Habib, and D. J. Fauth, J. Org. Chem., 1980, 45, 3860.

D.V. Sokolskii, T. 0. Omarkulov, U. Suyunbaev, 0. V. Vyaznikovtseva, and E. M. Mekeev,
Zzv. Akad. Nauk Kaz. SSR, Ser. Khim., 198 I , 13.
E. M. Sulman, 0. B. Sannikov, 0. S. Popov, T. V. Ankudinova, M. K. Shakhova, and G. I.
Samokhvalov, Khim.-Farm. Zh., 1980, 14, 94.
G.Englert and M. Vecchi, Helv. Chim. Acta, 1980, 63, 1711.
K. Eskins and L. Harris, Photochem. Photobiol., 1981, 33, 131.
R. A. Alvarez, C. D. B. Bridges, and S.-L. Fong, Invest. Ophthalmol. Visual Sci., 1981, 20, 304.
H.Stuerle, J. Chromatogr., 1981, 206, 319.
A. C. Ross, Anal. Biochem., 1981,115, 324.
M. Leclercq and M. Bourgeay-Causse, Rev. Inst. Pasteur Lyon, 1981, 14, 475.
J. G. Besner, R. Leclaire, and P. R. Band, J. Chromatogr., 1980, 183, 346.
G. Palmskog, J. Chromatogr., 1980, 221, 345.
D.M. A. Mousdale, J. Chromatogr., 1981, 209,489.
D.R.Janero and R. Barnett, Anal. Biochem., 1981, 111, 283.
S. W. Jeffrey, Limnol. Oceanogr., 1981, 26, 191.
256
has been reviewed.137A study of different adsorbents for column chromatography

of p-carotene, canthaxanthin, lutein, zeaxanthin, isozeaxanthin, and astaxanthin
esters revealed that decomposition occurred most extensively on silica gel, but
could be prevented by pretreatment of the silica with edta.13*Recovery of retinyl
phosphates from silicic acid increased from 15 /, to 85 % in the presence of 0.5 %
trieth~1amine.l~~
A fluorimetric method for the determination of all-trans-retinol in serum has
been described.140Radioimmunoassay procedures for the determination of retinol
in serum are as sensitive as h.p.l.c.,lgl and can be used for determining retinol
a n a l 0 g ~ e s . lAn
~ ~ immunoassay procedure has also been developed for abscisic
which can also be determined by g.1.c. of its methyl ester.144
N.M.R. Spectroscopy. High-resolution n.m.r. has proved to be a very powerful
method for studying and determining the configurations of cis-isomeric carotenoids.
The full IH n.m.r. characterization of nine mono-cis- and di-cis-isomers of astaxanthin diacetate has been published.126Details of a 13C n.m.r. study of the 9-cis-,
13-cis-, 9-cis-, and 13-cis-isomers of lutein (35) and capsanthin [3,3-dihydroxy-p,
x-caroten-6-one (196)] have been
The conformation and energytransfer properties of the carotenoporphyrin ester (77) have been studied by
n.m.r.146Samples of bacteriorhodopsin obtained by enrichment with [ 14-l3C1]and [ 15-13C,]-retinaldehydehave been investigated by 13C n.m.r.lg7
Circular Dichroism. The normally achiral carotenoids echinenone (1 1) and canthaxanthin (10) exhibit c.d. when bound as the chromophore of the violet carotenoprotein of the fly Rhynchosciara a m e r i ~ a n aInteraction
.~~
of lutein (35) with ovalbumin and related proteins gave a complexwith a changed absorption spectrum and
strong c.d. at around 384 nm suggesting aggregation of the lutein in a chiral form.148
P-Cryptoxanthin (1 97) behaved similarly, but canthaxanthin and ethyl 8-apo-pcaroten-8-oate (1 98) showed no c.d. bands, even though they formed complexes.149
C.d. analysis has also been used to investigate the organization of carotenoids in
phospholipid vesicles and membranes.lso The c.d. spectrum of sodium cholatesolubilized rhodopsin has been determined.151
13
138
139
140
141
142
143
144
145
146
14
148
149
lS0
161
Z . Sestak, Photosynthetica, 1980, 14, 239.

Y. Tanaka, T. Katayama, K. L. Simpson, and C. 0. Chichester, Bull. Jpn. SOC.Sci. Fisheries,
1981, 47, 799.
J. Frot-Coutaz, R. Letoublon, B. Gautier, and R. Got, Anal. Lett., 1981, 14, 69.
S.-C. Wu, A. C. Capomacchia, and J. C. Price, J . Pharm. Sci., 1981, 70, 685.
S. S. Westfall and G. H. Wirtz, Experientia, 1980, 36, 1351.
G. H. Wirtz and S. S. Westfall, J . Lipid Res., 1981, 22, 869.
S. M. Sircar, P. K. Sircar, P. K. Nagar, R. I. Iyer, and K. Chattopadhyay, Plant Biochem. J.,
1980, 7, 83.
K. A. Karavaeva, A. A. Bezzubov, and N. P. Korableva, Biokhim. Melody, 1980, 185.
M. Baranyai, P. Molnar, J. Szabolcs, L. Radics, and M. Kajtar-Peredy, Tetrahedron, 1981,37,
203.
A. L. Moore, G. Dirks, D. Gust, and T. A. Moore, Photochem. Photobiol., 1980, 32, 691.
A. Yamaguchi, T. Unemoto, and A. Ikegami, Photochem. Photobiol., 1981, 33, 511.
S. Takagi, M. Shiroishi, and T. Takagi, Agric. Biol. Chem., 1980, 44, 2111.
S. Takagi, M. Shiroishi, and T. Takagi, Agric. Biol. Chem., 1981, 45, 1159.
M. Cheron and J. Bolard, C.R. Hebd. Seances Acad. Sci.,Ser. 3, 1981, 292, 1125.
J. Wagner, E. Smith, and M. A. Cusanovich, Photochem. Photobiol., 1981, 33, 929.
257
Raman and Infrared Spectroscopy. Two reviews deal with resonance Raman
spectroscopy of carotenoid-containing biomolecules and rnicro-organism~~~~
and
of carotenoids and chlorophylls in photosynthetic bacteria.153 The resonance
Raman excitation profile of lycopene in acetone has been determined.154Calculations previously used for p-carotene do not explain the lycopene data. Several
papers report detailed studies of the time-resolved resonance Raman spectra of
(196) R1= a, R2= b

(197) R1= a, R2 = c
(198) R1= C, R2 = C02Et
(199) R1= C, R2 = CHO

(200) R1= R2= CH=CHCO,Me
(201) R1= R2 = b
the lowest excited triplet states of all trans-p-carotene, all-trans-retinaldehyde,and

all-trans-~anthaxanthin.~~~-~~~
A coherent anti-Stokes lineshape analysis has been
performed for P-carotene.160The de-excitation lifetime of P-carotene, singlet state,
has been deterrnined161as < 1 ps. Changes in the molecular geometry of P-carotene
on electronic excitation have been determined by high-resolution resonance
Raman spectroscopy.162A model has been applied to the excitation profile of 8carotene to explain Raman line-br0adeni11g.l~~
The Raman and i.r. bands of retinaldehyde were markedly affected in the presence of water, owing to hydrogenb0nding.1~~
The authors conclude that these results cast doubt on the ability of the
resonance Raman technique alone to detect the chemical state of the chromophore
in rhodopsin cyclic intermediates. Carotenoid-phycocyanin interactions in
Anacystis nidulans have been investigated by carotenoid resonance Raman spectro-
W. H. Nelson, Am. Lab., 1981, 13, 94.

M. Tasumi, Kagaku Sosetsu, 1980, 28, 249.
L. C. Hoskins, J. Chem. Phys., 1981, 74, 882.
R. Wilbrandt, N.-H. Jensen, P. Pagsberg, A. H. Sillesen, and K. B. Hansen, C.R. Conf. Int.
Spectrosc. Raman, 7th, ed. W. F. Murphy, N.R.C.C., Ottawa, 1980, p. 632.
N.-H. Jensen, R. Wilbrandt, P. B. Pagsberg, A. H. Sillesen, and K. B. Hansen, J . Am. Chem.
lba
lS3
lS4
ls5
lS6
SOC.,1980, 102, 7441.

16'
158
lS0
160
16a
16s
164
R. Wilbrandt and N.-H. Jensen, Eer. Bunsenges. Phys. Chem., 1981, 85, 508.
R. Wilbrandt and N.-H. Jensen, J . Am. Chem. SOC.,1981,103, 1036.
G. H. Atkinson, J. B. Pallix, T. B. Freedman, D. A. Gilmore, and R. Wilbrandt, J . Am.
Chem. SOC.,1981, 103, 5069.
P. K. Dutta, R. Dallinger, and T. G . Spiro, J . Chem. Phys., 1980, 73, 3580.
R. F. Dallinger, W. H. Woodruff, and M. A. J. Rodgers, Photochem. Photobid., 1981,33, 275.
A. V. Lukashin and M. D. Frank-Kamenetsky, Chem. Phys. Lett., 1981, 80, 119.
K. Kodama and A. D. Bandrauk, Chem. Phys. Lett., 1981, 80, 248.
A. E. Allan and A. Cooper, FEBS Lett., 1980, 119, 238.
4
258
~ c 0 p y .A
l ~detailed
~
resonance Raman study of invertebrate astaxanthin-proteins
has been published.166
Many papers report resonance Raman studies of the retinaldehyde-protein
visual pigments and bacteriorhodopsin. A Symposium proceedings
contains several, including review article^.^^^-^^* Papers published elsewhere deal with
resonance Raman spectroscopic studies of rhodopsin and intermediates in the
visual
including deuterium-labelled ana10gues.l~~
Resonance Raman
studies on bacteriorhodopsinare covered in a review174and a number of p a p e r ~ . l ~ ~ - l ~ l
Hydrogen-bonding between the trans-N-retinylidene-butylamine Schiff base
and phenols has been studied by i.r. spectroscopy.ls2
Electronic Absorption Spectroscopy. The pressure dependence of the absorption
spectrum of p-carotene in pentane-isopentane, up to 60 kbar, has been studied.ls3
A large red shift and broadening of vibronic peaks was observed. The absorption
spectra of charge-transfer complexes of trans-p-carotene, 8-apo-p-caroten-8-al
(1 99), astacene (83), and methylbixin(200) have been determined.ls4The orientation
of P-carotene and retinaldehyde in lipid bilayers has been investigated.ls5Agreement was found between the theory of elastic light scattering accompanying light
absorption and the blue part (but not the red part) of the absorption bands of three
carotenoids.ls6
U.V.spectra have been reported for the 9 4 s - and all-trans-G, and -C1,, and the
all-trans-C,, and -CZ4homologues of retin01.l~~
Several retinaldehyde isomers in
iso-octane solution with [Eu(fod),] gave a new characteristic absorption band.les
B. Szalontai and M. Van de Ven, FEBS Lett. , 1981, 131, 155.

R. J. H. Clark, N. R. DUrso, and P. F. Zagalsky, J. Am. Chem. SOC.,1980, 102, 6693.
167 C.R. Conf. Int. Spectrosc. Raman, 7th, ed. W. F. Murphy, N.R.C.C., Ottawa, 1980.
lB8
M. A. El-Sayed, in Ref. 167, p. 542.
lBD
A. Warshel and R. M. Weiss, in Ref. 167, p. 552.
170 A. Lewis, in Ref. 167, p. 556.
171 D. Narva and R. H. Callender, Photochem. Photobiol., 1980, 32, 273.
G. Hayward, W. CarIsen, A. Siegman, and L. Stryer, Science, 1981, 211, 942.
173 R. Mathies, G. Eyring, B. Curry, A. Broek, I. Palings, R. Fransen, and J. Lugtenburg, in Ref.
167, p. 546.
174 M. A, El-Sayed, Springer Ser Opt. Sci., 1981, 26, 295.
17b A. G. Doukas, A. Pande, T. Suzuki, R. H. Callender, B. Honig, and M. Ottolenghi, Biophys. J.,
1981, 33, 275.
176 M. Braiman and R. Mathies, Biochemistry, 1980, 19, 5421.
B. Ehrenberg, A. T. Lemley, A. Lewis, M. Von Zastrow, and H. L. Crespi, Biochim. Biophys.
Acta, 1980, 593, 441.
178 P. V. Argade, K. J. Rothschild, A. H. Kawamoto, J. Herzfeld, and W. C. Herlihy, Proc. Natl.
Acad. Sci. USA, 1981, 78, 1643.
178 B. Szalontai, Biochem. Biophys. Res. Commun., 1981, 100, 1126.
180 C.-L. Hsieh, M. Nagumo, M. Nicol, and M. A. El-Sayed, J. Phys. Chem., 1981, 85, 2714.
lS1 T. Alshuth and M. Stockburger, Ber. Bunsenges. Phys. Chem., 1981, 85, 484.
lB2 P. P. Rastogi and G. Zundel, Biochem. Biophys. Res. Commun., 1981,99, 804.
ls3 Z. Z. Ho, T. A. Moore, S. H. Lin, and R. C. Hanson, J. Chem. Phys., 1981, 74, 873.
lS4 B. Mallik, K. M. Jain, and T. N. Misra, Biochem. J., 1980, 189, 547.
l E 6 L. B. A. Johansson, G. Lindblom, A. Wieslander, and G. Arvidson, FEBSLett., 1981, 128,97.
I. Z. Steinberg and J. Anglister, Ann. N. Y. Acad. Sci., 1981, 336, 125.
l E 7 P. K. Das and R. S. Becker, Photochem. Photobiol., 1980, 32, 739.
la8A. B. Ellis, R. Schreiner, and R. A. Ulkus, Proc. Natl. Acad. Sci. USA, 1981, 78, 3993.
lBb
lB6
259
Irradiation into this band caused photoisomerization, appreciable quantities of

the 11-cis-isomer being formed. Several papers18g-191report calculations related
to the spectroscopicproperties of retinylidene Schiffbases. The principal absorption
axes of rhodopsin and prelumirhodopsin have been determined.lg2
Photoacoustic Spectroscopy. The photoacoustic spectra of visual pigments have
been reported.lg3
Miscellaneous Physical Chemistry. The naphthalene-sensitized formation of triplet
@-carotenehas been studied.lg4The lifetime of the excited singlet state of P-carotene
has been discussed in relation to photosynthetic light harvesting.lg5Laser flash
photolysis of the haematoporphyrin-P-carotene
and the photoconductivity of carotenoid-containing bilayer lipid membraneslg7have been reported.
Ground-state dipole moments of all-trans- and 9-cis-retinaldehyde have been
determined from solution dielectric constant rneasurement~.~~~
Hydrophobic bond
energies of 1l-cis-retinaldehyde and P-ionone have been
The production of transient radical anions in the pulse radiolysis of retinyl polyenes has
been studied.200
Photoreceptor Pigments. Light-energy transduction mechanisms in visual cells11
and the bacteriorhodopsin system of Halobacteriuml2 are the subjects of two
Symposium proceedings. Several other r e v i e w ~ ~deal
~ l -with
~ ~ ~aspects of the same
topics. Of the very many original papers on visual pigments, some report aspects
of the chemistry and spectroscopic properties of the retinaldehyde chromophore
of r h o d o p ~ i n ~and
~ ~ rhodopsin
-~l~
a n a l o g ~ e s . ~The
~ ~ -chemistry,
~~'
photochemistry,
K. Ishikawa, T. Yoshihara, and H. Suzuki, J. Phys. SOC.Jpn., 1980, 49, 1505.

J. M. Leclercq and C. Sandorfy, Photochem. Photobiol., 1981, 33, 361.
K. Nakachi, K. Ishikawa, and H. Suzuki, J. Phys. SOC.Jpn., 1981, 50, 617.
lg2 B. D. Gupta, Biophys. Struct. Mech., 1980,7, 97.
Ig3 F. Boucher and R. M. Leblanc, Biochem. Biophys. Res. Commun., 1981, 100, 385.
19* N.-H. Jensen, R. Wilbrandt, and P. B. Pagsberg, Photochem. Photobiol., 1980, 32, 719.
lg5 R. F. Dallinger, W. H. Woodruff, and M. A. J. Rodgers, Photochem. Phorobiol., 1981,33, 275.
lQ6A. Poletti, S. M. Murgia, and S. Cannistraro, Photobiochem. Photobiophys., 1981, 2, 167.
lg7 J. Kutnik and Z . Lojewska, Stud. Biophys., 1981, 82, 127.
lgE
A. B. Myers and R. R. Birge, J. Am. Chem. SOC.,1981,103, 1881.
lg0 T, Kakitani, H. Kakitani, and S. Yomosa, Biophys. Struct. Mech., 1980, 7, 101.
mo N. V. Raghavan, P. K. Das, and K. Bobrowski, J. Am. Chem. SOC.,1981,103,4569.
201 R. R. Birge, Ann. Rev. Biophys. Bioeng., 1981, 10, 315.
B. Honig, Ann. N.Y. Acad. Sci., 1981, 367, 269.
803 P. M. Rentzepis and P. F. Barbara, Adv. Chem. Phys., 1981, 47, 627.
204 S. P. Balashov and F. F. Litvin, Biojizika, 1981, 26, 557.
zo6 W. Stoeckenius, Acc. Chem. Res., 1980, 13, 337.
208 A. E. Allan and A. Cooper, FEBS Lerr., 1980,119, 238.
207 N. Bennett, Biochem. Biophys. Res. Commun., 1980, 96, 1695.
208 R. R. Birge and L. M. Hubbard, Biophys. J., 1981, 34, 517.
2oQ A. G. Doukas, P. Y. Lu, and R. R. Alfano, Biophys. J., 1981, 35, 547.
alo G. Hayward, Science, 1981,211, 942.
211 M. Nanasawa and H. Kamogawa, Bull. Chem. SOC.
Jpn., 1981, 51, 1104.
81z T. Suzuki and R. H. Callender, Biophys. J., 1981, 34, 261.
T. Suzuki and M. Makino, Biochem. Biophys. Acta, 1981, 636, 27.
a14 M. R. Fransen, I. Palings, and J. Lugtenburg, Recl. Trav. Chim. Pays-Bas, 1980, 99,384.
a16 B. Mao, M. Tsuda, T. G. Ebrey, H. Akita, V. Balogh-Nair, and K. Nakanishi, Biophys. J.,
IEg
IDO
1981, 35, 543.

116
217
Y . Shichida, A. Kropf, and T. Yoshizawa, Biochemistry, 1981, 20, 1962.

P. Towner, W. Gaertner, B. Walckhoff, and D. Oesterhelt, Eur. J. Biochem., 1981, 117, 353.
260
and spectroscopy of the chromophore of b a c t e r i o r h o d o p ~ i n ~and

~ ~ -analogues
~~~
prepared from retinaldehyde analogues 224-229 are also the subject of several papers.
Biosynthesis and Metabolism.--Biosynthesis. Carotenoid biosynthesis is dealt with

extensively in the book by Goodwinl and the chapter by Spurgeon and Porter,2
(202) R1= a, R2= b

(203) R1= R2= a
and is the subject of other more specific review^.^^^^ Several papers report studies
of carotenoid biosynthesis and transformations in cell-free systems. The capsanthin-synthesizing activity of Capsicum annuum chromoplasts has been studied
extensively. The incorporation of labelled acetate, mevalonate, and isopentenyl
pyrophosphate into capsanthin (1 96) and capsorubin [3,3-dihydroxy-x,x-carotene6,6-dione (201)]has been demonstrated,231and the incorporation of antheraxanthin
[5,6-epoxy-5,6-dihydro-p,p-carotene-3,3-diol
(202)J into capsanthin and of violaxanthin [5,6,5,6-diepoxy-5,6,5,6-tetrahydro-p,p-carotene-3,3-diol
(203)] into
capsorubin are r e p ~ r t e d . Labelling
~ ~ ~ * ~ studies
~~
with isopentenyl pyrophosphate
suggest that, in Capsicum, cis-trans isomerization occurs at the level of phyto(204)
Isolated chromoplasts of
fluene [7,8,11,12,7,8-hexahydro-$,$-carotene
Narcissus pseudonarcissus synthesize phytoene [7,8,11,12,7,811,12-octahydro-+,
21 a
21 8
220
221
222
2 23
224
S. P. Balashov and F. F. Litvin, Photobiochem. Photobiophys., 1981, 2, 111.

T. Iwasa, F. Tokunaga, and T. Yoshizawa, Biophys. Struct. Mech., 1980, 6, 253.
0. Kalisky, M. Ottolenghi, B. Honig, and R. Korenstein, Biochemistry, 1981, 20, 649.
T, Kouyama, Y. Kimura, K. Kinosita, and A. Ikegami, FEBS Lett., 1981, 124, 100.
W. Maentele, F. Siebert, and W. Kreutz, FEBSLett., 1981, 128, 249.
P. C. Mowery and W. Stoeckenius, Biochemistry, 1981, 20, 2302.
H. Bayley, R. Radhakrishnan, K.-S. Huang, and H. G. Khorana, J . Biol. Chem., 1981, 258,
3797.
225
226
B. Mao, R. Govindjee, T. G. Ebrey, M. Arnaboldi, V. Balogh-Nair, K. Nakanishi, and R.

Crouch, Biochemistry, 1981, 20, 428.
K. Nakanishi, V. Balogh-Nair, M. Amaboldi, K. Tsujimoto, and B. Honig, J . Am. Chem.
SOC.,1980, 102, 7945
227
22 8
229
P. G. Kryukov, Y. A. Lazarev, Y. A. Matveets, E. L. Terpugov, L. N. Chekulaeva, and A. V.

Sharkov, Stud. Biophys., 1981, 82, 101.
F. Tokunaga, T. G . Ebrey, and R. Crouch, Photochem. Photobiol., 1981, 33, 495.
P. Towner, W. Gaertner, B. Walckhoff, D. Oesterhelt, and H. Hopf, FEBS Lett., 1980, 117,
367.
230
231
232
a33
B. Camara and J. Brangeon, Pfanta, 1981, 151, 359.

B. Camara and R. Moneger, Dev. Plant Biol., 1980, 6, 363.
B. Camara and R. Monkger, Biochem. Biophys. Res. Commun., 1981, 99, 1117.
B. Camara, C. Payan, A. Escoffier, and R. Moneger, C.R. Hebd. Seances Acad. Sci., Ser. D.,
1980, 291, 303.
Car0tenoids and Poly terpeno ids
26 1
(204) R1= a, R2= b

(205) R1= R2= b
(206) R1= R2= c
(207) R1= d, R2= a
(208) R1= d, R2= c
(209) R1= R2= a

(210) R1= e, R2= c
+-carotene (205)] and p-carotene from isopentenyl p y r o p h ~ s p h a t eDesaturation

.~~~
was inhibited by SAN 6706, but nicotine did not cause lycopene [$,$-carotene
(206)] to accumulate. A cell-free system from Phycomyces blakesleeanus incorporated mevalonate into p h y t ~ e n e In
. ~ Neurospora
~ ~ ~ ~ ~ ~crassa, the ability to
synthesize phytoene from mevalonate was located in the plasma and endoplasmic
reticulum membrane fractions.237
The use of inhibitors in studies of carotenoid biosynthesis continues. In Micrococcus roseus, canthaxanthin synthesis is .inhibited by nicotine (P-zeacarotene
[7,8-dihydro-p,+-carotene(207)] accumulates), piperonyl butoxide (phytoene
accumulates), and CPTA (p-zeacarotene, y-carotene [P,Jr-carotene (208)], and
their hydroxy-derivatives accumulate).238It was suggested that cyclization occurs
at the <-carotene [7,8,7,8-tetrahydro-+,$-carotene
(209)] stage, and hydroxylation
at the p-zeacarotene stage. The conversion of pools of lycopene, accumulated in
the presence of nicotine, into chlorobactene [cp,+-carotene (210)] by Chlorobium
Nicotine also inhibits p-carotene formation in
limicola has been
Leptosphaeria michotii, and lycopene accumulates.24oThe influence of compounds
structurally related to trisporic acid (2 11) on carotenogenesis in BZakeslea trispora
has been
234
235
238
237
238
230
240
241
P. Beyer, K. Kreuz, and H. Kleinig, Planta, 1980, 150, 435.

G. Sandmann, W. Hilgenberg, and P. Boger, Z . Naturforsch., Teil C, 1980, 35, 927.
G. Sandmann, P. M. Bramley, and P. Boger, Pesticide Biochem. Physiol., 1980, 14, 185.
U. Mitzka-Schnabel and W. Rau, Phytochemistry, 1981, 20, 63.
J. J. Cooney and R. A. Berry, Can. J. Microbiol., 1981, 27, 421.
L. S. Leutwiler and D. J. Chapman, Plant CellPhysiol., 1981, 22, 781.
S. Jerebzoff-Quintin and S. Jerebzoff, Protoplasma, 1980, 104, 43.
I. M. Yakovleva, L. A. Vakulova, E. P. Feofilova, M. N. Bekhtereva, and G. I. Samokhvalov,
Mikrobiologiya, 1980, 49, 199.
262
Three reviews discuss the photoregulation of carotenoid biosynthesis in microo r g a n i s m ~ . ~Other

~ - ~papers
~ ~ + report
~ ~ ~ various aspects of the photoinduction and
photoregulation of biosynthesis in the fungi Neurospora crassa244-249
and Phycomyces b l a k e s l e e a n ~ sand
~ ~ in
~ *Brevibacterium
~~~
s u I f u r e ~ mand
~ ~Mycobacterium
~
~ m e g m a t i s Genetic
. ~ ~ ~ studies with Phycomyces have led to the suggestion of an
important genetically controlled transfer of substrate (lycopene) to the cyclizing
The involvement of cyclic AMP as mediator of trisporic acid
biosynthesis in B. trispora has been reported.256
Metabolism. The Japanese catfish Parasilurus asotus metabolizes zeaxanthin (27)
into parasiloxanthin [7,8-dihydro-P,P-carotene-3,3-diol
(212)] and 7,8-dihydro(213)].257Lutein (35)
parasiloxanthin [7,8,7,8-tetrahydro-P,P-carotene-3,3-diol
R2
X
2
HO
A- &.
HO
HO
0
C
(212)
(213)
(214)
(215)
(216)
842
243
844
245
246
241
*48
248
a60
851
a62
263
864
R1= R2 = a, X1 = CH2CH2,X2 = CH=CH

R1= R2 = a, X1 = X2 = CH,CH2
R1= a, R2 = b, X1 = CH2CH2,X2 = CH=CH
X2 = CH=CH
R1= c, R2 = a,
R1= C, R2 = b,
X2 = CH=CH
W. Rau, in Blue Light Syndrome, ed. H. Senger, Springer, Berlin, 1980, p. 283.
W. Rau, in Pigments in Plants, 2nd Edn., ed. F.-C. Czygan, Gustav Fischer, Stuttgart and
New York, 1980, 1981, p. 80.
E. L. Schrott, in Blue Light Syndrome, ed. H. Senger, Springer, Berlin, 1980, p. 309.
E. L. Schrott, Planta, 1980, 150, 174.
E. L. Schrott, Planta, 1981, 151, 371.
M. S. Kritsky and E. K. Chernysheva, Dokl. Akad. Nauk SSSR, 1980,255,228.
M. S. Kritsky, V. Y. Sokolovsky, T. A. Belozerskaya, and E. K. Chernysheva, Dokl. Akad.
Nauk SSSR, 1981, 258, 759.
R. W. Harding and R. V. Turner, Plant Physiol., 1981,68, 745.
B. D. Whitaker and W. Shropshire, jun., Exp. Mycol., 1981, 5, 243.
I. Lopez-Diaz and E. Cerda-Olmedo, Planta, 1980, 150, 134.
Y. Koyama, Y. Yazawa, K. Kato, and S . Yamagishi, Chem. Pharm. Bull., 1981, 29, 176.
F. Kato, Y. Koyama, S. Muto, and S. Yamagishi, Chem. Pharm. Bull., 1981, 29, 1674.
S. Torres-Martinez, F. J. Murillo, and E. Cerda-Olmedo, Genet. Res., 1980, 36, 299.
F. J. Murillo, S. Torres-Martinez, C. M. G. Aragon, and E. Cerda-Olmedo, Eur. J. Biochem.,
1981,119, 511.
*66
N. S. Govind and V. V. Modi, Indian J. Exp. Biol., 1981, 19, 544.

T. Matsuno and S . Nagata, Bull. Jpn. SOC.Sci. Fisheries, 1980, 46, 1191.
263
Curotenoids and Po iy terpen oids
was converted only into 7,8-dihydrolutein (214).a58In goldfish, Curussius uurutus,

lutein and zeaxanthin were metabolized to keto-derivative~.~~~
Thus zeaxanthin
gave p-doradexanthin (2 15) and astaxanthin, whereas lutein gave or-doradexanthin
(216). The incorporation of [ 15,l5-3H2]-P-caroteneinto astaxanthin and other
ketocarotenoids by the crab Clibunarius erythropus has been demonstrated.Z60 In
the intestines of the fishes Heteropneustesfossilis and Channa striatus, lutein underwent cleavage to 3-dehydroretinol [vitamin A2(217)].2s1
(217)
(218)
The conversion of trans-retinyl acetate into retinoic acid in hamster organ

culture,262and of cis- and trans-retinoic acid into the 5,6-epoxy- and 4-0x0derivatives and their glucuronides has been d e m o n ~ t r a t e d . ~ ~ ~ ~ ~ ~ ~
Strains of Aspergillus niger metabolize ionones and related compounds to
oxygenated derivatives, some of which may be useful intermediates for carotenoid
synthesis. The asymmetric oxidation of P-ionone to (2S,6R77R)-2,7-epoxydihydroa-ionone (218) has been
(R)-4-Hydroxy-p-ionone(219 ; X = OH)
(219) R
(-!5J*
x
(222) R
6. &*
(223) R
(224) R
@
0
T. Matsuno and S. Nagata, Bull. Jpn. SOC.Sci. Fisheries, 1980, 46, 1363.
T. Matsuno, H. Matsutaka, and S. Nagata, Bull. Jpn. SOC.Sci. Fisheries, 1981, 47, 605.
m0 R. Castillo, Comp. Biochem. Physiol., 1980, MA, 695.
261 U. C. Goswami and A. B. Barua, Zndian J. Biochem. Biophys., 1981,18, 88.
C. A. Frolik, L. L. Dart, and M. B. Sporn, Biochim. Biophys. Acta, 1981, 663, 329.
s63 H. F. DeLuca, M. Zile, and W. K. Sietsema, Ann. N . Y. Acad. Sci., 1981, 359, 25.
s64 C. A. Frolik, B. N. Swanson, L. L. Dart, and M. B. Sporn, Arch. Biochem. Biophys. 1981,208,
s68
a59
344.
s65
Y . Mikami, Y . Fukunaga, T. Hieda, Y . Obi, and T. Kisaki, Agric. Biol. Chem., 1981, 45, 331.
264
and (S)-2-hydroxy-p-ionone (220; X = OH) were the major products formed

from P-ionone by another A . niger strain, with 2-oxo-P-ionone (22 l), 4-oxo-pionone (222), 3,4-didehydro-p-ionone (223), 2,3-didehydro-4-oxo-(3-ionone
(224),
3,4-didehydro-2-oxo-p-ionone
(225), (S)-2-acetoxy-p-ionone (220; X = OAc), (R)4-acetoxy-p-ionine ( 2 I9 ; X = OAc), 5,6-epoxy-p-ionone (226), and the aryl
derivative (227) as minor products.266Isophorone gave the trimethylcyclohexanone
derivatives (228)-(23 l).267
2 Polyterpenoids and Quinones
Po1yterpenoids.-The cleomeprenols from Cleorne ~ p i n o s a and

* ~ ~the malloprenols
from MaZlotzrsj a p o n i c ~each
s ~ ~consist
~
of a mixture of cis-trans C4o-C55 isoprenoid
alcohols (232), formed by addition of cis-isoprene units from isopentenyl pyrophosphate to all-trans-geranylgeranylpyrophosphate. The C55component, referred
to as moraprenol, has been converted chemically into the diphosphate-sugar
derivative.27013C N.m.r. relaxation times have been used to identify the cis- and
trans-methyl groups of terminal isoprene residues in isoprenoids :271 the cis-methyl
group has the longer Tl. A method has been developed for the preparation of
stereochemically pure 1,5-dienes by coupling allylic p-tolylsulphones with an allylic
bromide.272Thus reaction of trans-bromogeranyl acetate (233) with the sulphone
(232) n = 3-6
(233) X = Br, R = OAc

(234) X = H, R = S0,PhMe
(236) X
(237) X
266
267
268
269
270
272
= OMe,
= Me,
=
=9
1-10
or 10
Y . Mikami, Y . Fukunaga, M. Arita, and T. Kisaki, Appl. Environ. Microbiol., 1981, 41, 610.
Y. Mikami, Y. Fukunaga, M. Arita, Y. Obi, and T. Kisaki, Agric. Biol. Chem., 1981,45, 791.
T. Suga and T. Shishibori, J . Chem. SOC.,Perkin Trans. 1, 1980, 2098.
T. Suga, T. Shishibori, and K. Nakaya, Phytochemistry, 1980, 19,2327.
L. L. Danilov, D. Maltsev, V. N. Shibaev, and N. K. Kochetkov, Caubohydr. Res., 1981, 88,
203.
A. Okubo, H. Kawai, T. Matsunaga, T. Chuman, S. Yamazaki, and S . Toda, Tetrahedron
Lett., 1980, 21, 4095.
K. Sato, S. Inoue, A. Onishi, N. Uchida, and N. Minowa. J . Cfiem.SOC.,Perkin Trans. I , 1981,
761.
265
Carotenoids ctnd Polyterpenoids
(234) followed by reductive elimination gave all-trans-geranylgeraniol (235).

Higher analogues (C45and C5Jwere prepared by the same route.
Isoprenylated Quinones.-A review has been published on the chemistry and biochemistry of ubiquinone (236) and plastoquinone (237) in plants.273
Chemistry. Methods have been presented for the preparation of sulphone-functionalized prenylhydroquinone~.~~~
Thus the ubiquinol (238), plastoquinol (239), and
OMe
OMe
S0,Ph
OMe
(238) X = Me0
(239) X = Me
OMe
OMe
OMe
(241) X = Me0
(242) X = Me
OMe
(243)
naphthoquinol ethers (240) were obtained by reaction of the corresponding bromides

(241), (242), and (243) with magnesium and the sulphone (244). The regio- and
stereo-selective synthesis of ubiquinones-2-10 (236 ; n = 2-10), phylloquinone
(245), and related polyprenylquinones has been described.27s Chemical model
studies for the mechanism of vitamin K [phylloquinone or menaquinone (246)]

epoxide reductase have been
The mechanism of photo-oxidation of
menaquinone-1 (246; n = 1) to the hydroperoxide (247) has been investigated.277
274
276
277
H. K. Lichtenthaler, Dev. Plant Biol.,1980, 6, 299.

Y . Fujita, M. Ishiguro, T. Onishi, and T. Nishida, Synthesis, 1981, 469.
Y . Naruta, J. Org. Chem., 1980, 45, 4097.
R. B. Silverman, J . Am. Chem. SOC.,1981, 103, 5939.
D. Creed, H. Werbin, and T. Daniel, Tetrahedron Lett., 1981, 22, 2039.
266
Physical Methods. H.p.1.c. procedures for the separation and assay of ubiquinone
and h o m o l o g ~ e s ~and
~ ~of- ~menaquinone
~~
cis- and trans-isomers, 2,3-epoxides,
and chain-length homo10guesZ81~282
have been described. A lH n.m.r. study has
been reported2B3of the location and motion of ubiquinones in perdeuteriated phosphatidylcholine bilayers. Other aspects of the interaction of ubiquinone with
phospholipid monolayers have been
Biosynthesis. An alternative pathway has been proposed for the early stages of the
biosynthesis of the isoprenoid side-chain of ubiquinone in bacteria, via acetolactate
acid (248)286and
rather than a c e t o a ~ e t a t e 3,4-Dihydroxy-5-hexaprenylbenzoic
.~~~
(248) R = H
(249) R = Me
3-methoxy-4-hydroxy-5-hexaprenylbenzoic
acid (249)287have been identified as
intermediates in the biosynthesis of ubiquinone-6 in Saccharomyces cerevisiae. In
Escherichia coli, an enzyme-complex-bound pool of 2-octaprenylphenol (250)
accumulated under anaerobic conditions, and was rapidly converted into ubiquinone-8 in air.288The enzymic synthesis of o-succinylbenzoate,z89the conversion
of this into its coenzyme A thioester, and the cyclization of this to 1,4-dihydroxy2-naphthoic acid (25 1)290 have been demonstrated with bacterial cell-free preparations. Micrococcus luteus membrane fractions catalysed the prenylation of (251)
by C15-C4, prenyl pyrophosphates en route to m e n a q u i n ~ n e The
. ~ ~ chloroplast
~
envelope has been reported as the site of (25 1) prenylation by phytyl pyrophosphate
in phylloquinone b i o s y n t h e s i ~Several
. ~ ~ ~ genetic studies of bacterial menaquinone
biosynthesis have been d e ~ c r i b e d . ~Two
~ ~ -papers
~ ~ ~ report the formation of
plastoquinone (237) in spinachzg6and lettucesg7chloroplasts,
G. Katsui, Bitamin, 1981, 55, 305.
M. D. Collins and D. Jones, J . Appl. Bacteriol., 1981, 51, 129.
2no S. Ikenoya, M. Takada, T. Yuzuriha, K. Abe, and K. Katayama, Chem. Pharm. Bull., 1981,
29, 158.
281 Y . Haroon, M. J. Shearer, and P. Barkhan, J . Chromatogr., 1980, 200, 293.
282 Y . Haroon, M. J. Shearer, and P. Barkhan, J . Chromatogr., 1981, 206, 333.
283 P. B. Kingsley and G . W. Feigenson, Biochim. Biophys. Acra, 1981, 635, 602.
284 P. J. Quinn, Biochem. hr., 1980, 1, 77.
2n5 S. Pandian, S. Saengchjan, and T. S . Raman, Biochem. J . , 1981, 196, 675.
z86 R. R. Goewert, C . J. Sippel, and R. E. Olson, Biochemistry, 1981, 20, 4217.
287 R. R. GoewFrt, C . J. Sippel, M. F. Grimm, and R. E. Olson, Biochemistry, 1981, 20, 5611.
H. E. Knoll, FEMS Microbial. Lett., 1981, 10, 59, 63.
28B R. Meganathan, J . Biol. Chem., 1981, 256, 9386.
L. Heide and E. Leistner, FEBS Lett., 1981, 128, 201.
*B1 Y . Saito and K. Ogura, J . Biochem. Tokyo, 1981, 89, 1445.
2s2 G. Schultz, B. H. Ellerbrock, and J. Soll, Eur. J . Biochem., 1981, 117, 329.
J. R. Guest and D. J. Shaw, Mol. Gen. Genet., 1981, 181, 379.
zB4 R. Meganathan, R. Bentley, and H. Taber, J . Bacteriol., 1981, 145, 328.
28s H. W. Taber, E. A. Dellers, and L. R. Lombardo, J . Bacteriol., 1981, 145, 321.
8B6 J. Soll, M. Kemmerling, and G . Schultz, Arch. Biochem. Biophys., 1980, 204, 544.
2B7 K. G . Hutson and D. R. Threlfall, Biochim. Biophys. Acta, 1980, 632, 630.
278
278
Part II
STEROIDS
1
Physical Methods
BY D. N. KIRK
1 Structure and Conformation
The Table beginning on p. 271 lists steroids whch have been the subject of X-ray
crystallographic studies during the year. Comment on the conclusions is limited
to only a few of the compounds.
X-Ray crystallographic study of synthetic (23S)-cholest-5-ene-3p,23,25-triol,
and comparison of the derived 23,25-dihydroxycholecalciferol(1) with a new
natural metabolite of vitamin D has established the configuration of the latter
compound.l Syntheses of the (25s)- and (25R)-isomers of 25,26-dihydroxycholecalciferol, using C 5precursors of known configuration to elaborate the sidechain, have established the configuration of the natural compound as (25s). The
configuration was confirmed by X-ray crystallographic analysis of the intermediate
compound (2).2
OAc
1
(4)
(3)
N. Ikekawa, T. Eguchi, Y.Hirano, Y.Tanaka, H. F. DeLuca, A. Itai, and Y.Iitaka, J . Chern.
SOC.,Chem. Commun., 1981, 1157.
R. Barner, J. Hubscher, J. J. Daly, and P. Schonholzer, Helv. Chim. A d a , 1981, 84, 915.
269
270
The use of X-ray diffraction to assign structures to unusual steroid derivatives

has been briefly r e ~ i e w e d .It~ includes reference to brassinolide (3), a steroidal
plant growth hormone. Another unusual product assigned its structure by the
X-ray method is the spiro-lactone (4), derived by thallium triacetate oxidation of
5a-~holestane-3,4-dione.~
The C- 17 configurations of the epimeric 17-ethynyl-14p-androstane- 14,17-diols
( 5 ) and (6) have been established by X-ray crystallographic s t ~ d y They
. ~ were
formed stereospecificallyby use of either LiC = CH or BrMgC = CMgBr (Scheme 1).
OH
/
CH
111
Scheme 1
(&)-17p-Hydroxy-8a-androst-4-en-3-0ne
crystallizes with molecules in two conformationally distinct forms.6 Ring A has the la-sofa conformation, but rings B
exist in two conformations, each deviating somewhat from the ideal twist and
characterized by small negative and positive torsion angles, respectively, about the
C-9-C-10 bond. Two polymorphic forms of 17~-acetoxy-6p-bromoandrost-4-en3-one exhibit markedly different crystal packings and solid-state i.r. spectra
although the conformations of individual molecules show only slight variation.
One polymorph comprises two conformers in I : 1 ratio, whereas the other contains
only a single conformer. It is concluded that in this case crystal packing has little
effect on molecular conformation, while causing changes in carbonyl stretching
frequencies. Crystalline cholesterol, with a bilayer structure, has hydrophilic
regions with parallel chains of hydrogen bonds. Side-chains exist in two distinct
conformations.8 The crystal habit of anhydrous cholesterol varies with solvent
J. Karle, Lipids, 1980, 15, 793.

A. M. Maione, A. Romeo, S. Cerrinc, W. Fedeli, and F. Mazza, Tetrahedron, 1981, 37, 1407.
J.-C. Beloeil, M. Bertranne, M. Fetizon, and T. Prange, J. Chem. SOC.,Chem. Commun.,1981,
363.
P. Chakrabarti, D . K. Banerjee, and K. Venkatesan, Steroids, 1981, 37, 269.

W. L. Duax, M. Numazawa, Y . Osawa, P. D. Strong, and C. M. Weeks,J. Org. Chem., 1981,
46, 2650.
H.-S. Shieh, L. G. Hoard, and C. E. Nordman, Acta Crystallogr., Ser. B, 1981,37,1538.
27 1
Physical Methods
and the degree of supersaturation of ~olution.~

The high-melting polymorph1 of
3a,7a-dihydroxy-5p-cholan-24-oicacid (chenodeoxycholic acid) has pairs of
molecules, with different conformations of their 17@-side-chains,forming an
asymmetric unit.ll
Insight into the photochemical reactions between deoxycholic or apocholic acid
(choleic acids) and guest molecules in crystalline inclusion complexes has been
obtained by X-ray studies. The choleic acids form channels with wall structures
determined by the nature of the guest molecule. Guest ketones of various types
react photochemically by addition to the choleic acid at a site determined by the
orientation of the ketone molecule in relation to the host (e.g. deoxycholic acid
reacts at C-5 or C-6 with linear aliphatic ketones, but at C- 16with cyclohexanone).12
Table Steroids studied by X-ray crystdogrdphy

(Compounds with references 1-12 are mentioned also in the text.)
Compound
Ref.
Oestranes
17P-Acetoxyoestr-4-en-3-one
2a-Fluoro-17 p-hydroxyoestr-4-en-3-one
17p-Hydroxy- 17a-methyloestra-4,9,1 l-trien-3-one
17~-Hydroxy-8a,l0a-oestr-4-en-3-one
dl-3-Methoxy-8a,l4p-oestra-l,3,5(
10),9(ll)-tetraene-l4,17a-diolmonohydrate
17a-Ethynyl-l7~-hydroxyoestranes
: see pregn-20-ynes, below
13
14
15
16
17
Androstanes
17p-Acetoxy-6 P-bromoandrost-4-en-3-one
17p-Hydroxy-7 a-methylandrost-5-en-3-one
dZ-17/3-Hydroxy-8a-androst-4-en-3-one
(8-isotestosterone)
17-Methoxy-16,17-seco-8a,13a-androsta-4,9(1
l)-diene-3,15,17-trione
17@-(5-Methyltetrazol-1-yl)-7a-aza-~-homoandrost-5-eno[7a,7-d]tetrazol-3
p-yl
acetate
6
18
6, 16
19
20
17a-Ethynyl-l7~-hydroxyandrostanes:
see pregn-20-ynes, below
Pregnanes
16a,l7a-Cyclopropanopregn-4-ene-3,20-dione
16a,l7a-Cyclobutanopregn-4-ene-3,20-dione
lo
I1
21
22
N. Garti, L. Karpuj, and S. Sarig, Cryst. Res. Techno[., 1981, 16, 1111.
M. C. Attwell, T. F. Massiah, R. A. Vergottini, and P. Ziegler, Belg. Pat. 879 844 1980,
P. F. Lindley, M. M. Mahmoud, F. E. Watson, and W. A. Jones, Acta Crystullogr. Ser. B,
1980,36, 1893.
R. Popovitz-Biro, H. C. Chang, C. P. Tang, N. R. Shochet, M. Lahav, and L. Leiserowitz,

Pure Appl. Chem., 1980,52, 2693.
la G. Precigoux, C. Courseille, and F. Leroy, Cryst. Struct. Commun., 1980, 9, 1005.
I4 D. C. Swenson, P. D. Strong, and W. L. Duax, Cryst. Strucr. Commun.,1981,10, 659.
G. Precigoux, B. Busetta, and S . Geoffre, Actu Crystullogr., Ser. B, 1981, 37,291.
M.M. Bhadbhade, P. Chakrabarti, D. K. Banerjee, and K. Venkatesan, Proc. Natl. Acud.
Sci. India, Sect. A, 1981, 47, 100.
l7 A. N. Chekhlov and S . P. Ionov, Bioorg. Khim., 1981, 7,436.
l 8 P. J. Cox, G. J. Mkandawire, and P. R. Mallinson, Actu Crystallogr., Ser. B, 1981, 37,727.
l9 D. C. N. Swindells, P. S. White, and 2.Valenta, Acta Crystullogr., Ser. B, 1981, 37, 263.
2o J. Husain, R. A. Palmer, H. Singh, T. R. Bhardwaj, and D. Paul, Actu Crystallogr. Ser. B,
l2
1981, 37, 205.

*l
V. M. Tseikinskii, V. B. Rybakov, V. I. Simonov, A. V. Kamernitskii, V. N. Ignatov, and I. S.

Levina, Bioorg. Khim., 1980, 6, 752.
V. M. Tseikinskii, V. B. Rybakov, V. I. Simonov, A. V. Kamernitskii, V. N. Ignatov, and I. S .
Levina, Bioorg. Khim., 1980, 6, 1872.
272
Compound
Ref
6a-Methyl-16
u , 17a-cyclohexanopregn-4-ene-3,20-dione
23
1 1 p,17a,21-Trihydroxypregn-4-ene-3,20-dione
(Cortisol)
24
1 1 ~,17a-Dihydroxy-21-iodopregn-4-ene-3,20-dione
24
21-Chloro-9a-fluoro-ll~-hydroxy-l6u,l7u-isopropylidenedioxypregn-4-ene3,20-dione
25
5a,14P-Pregn-20-yne-14,17a-diol
5
5a,14p,17P(H)-Pregn-20-yne-l4,17P-diol
5
18-Methyl-1l-methylene-19-nor-l7~(H)-pregn-4-en-20-yn-l7~-ol
26
17P-Hydroxy-l l ~-methoxy-l8-methyl-19-nor-17~(H)-pregna-4,9-dien-20-yn-3-one
27
17~-Hydroxy-l2-methyl-l7(3(H)-pregna-4,9,1
l-trien-20-yn-3-one
28
21-Bromo-9a-fluoro-1 1 p, 17aa-dihydroxy16P-methoxy-~-homo17-oxapregna39
1,4-diene-3,20-dione
Sterols and bile acids
Cholesterol
Cholesteryl hexanoate
Cholesteryl p-bromobenzoate
Cholest-5-ene-3
p,23(S),25-triol
2,4,6-Tribromocholest-4-en-3-one
(Z)-3~-Hydroxy-5(10)-secocholest-l(
lO)-en-5-one 3-p-bromobenzoate
3 ~,22(S),25(S),26-Tetrahydroxycholest-5-en-7-one
3,22,26-triacetate(2)
Brassinolide (3)
Spiro-lactone(4)(see text)
3a,7a-Dihydroxy-5
P-cholan-24-oicacid (chenodeoxycholic acid; high m.p.)
Deoxycholic acid-norbornadiene (2: 1) complex
Choleicacidinclusion complexes (see text)
8, 9
30
31
1
32
33
2
3
4
11
34
12
Cardenolides
3p, 14-Dihydroxy-12P-acetoxy-5P, 14P-card-20(22)-enolide

3a,14-Dihydroxy-5p, 14P-card-20(22)-enolide
p, 14p-card-20(22)-enolide
3P-Acetoxy-14-hydroxy-5
3p,16P-Acetoxy-(21R)-14,21-epoxy-5p,14P-card-20(22)-enolide
3~-Bromoacetoxy-l4-hydroxy-5p,14P-card-20(22)-enolide
3p,l6P-Diacetoxy-14-hydroxy-5P,14P-card-20(22)-enolide
3P,1 6$-Diacetoxy-l4-hydroxy-(21
R)-2 1-bromo-5P, 14P-card-20(22)-enolide
23
24
e6
26
27
28
30
s1
32
33
34
36
36
35
36
37
38
39
40
41
V. M. Tseikinskii, V. B. Rybakov, V. I. Simonov, A. V. Kamernitskii, L. E. Kulikova, and

I. S. Levina, Bioorg. Khim., 1980, 6, 1409.
E. E. Castellano, P. Main, and E. Westbrook, Acta Crystallogr., Ser. B, 1980, 36, 3063.
R. Ceolin, R. Julien, and N. Rodier, Acta Crystallogr., Ser. B, 1981, 37, 148.
F. J. Zeelen, Red. Trav. Chim. Pays-Bas, 1980, 99, 323.
J. Delettre, G. Lepicard, E. Surcouf, and J. P. Mornon, Acta Crysfallogr., Ser. B, 1981, 37,
1712.
G. Precigoux, F. Leroy, and S. Geoffre, Acta Crystallogr., Ser. B, 1980, 36, 3123.
C. M. Cimarusti, P. G. Grabowich, B. K. Toeplitz, and R.K. Varma,J. Urg. Chern., 1981,46,
803.
Y . Ja. Park and B. M. Craven, Taehan Hwahakhoe Chi., 1981, 25, 131.
A. P. Polishchuk, M. Y. Antipin, R. G. Gerr, V. I. Kulishov, Y. T. Struchkov, and V. G.
Tishchenko, Cryst. Struct. Commun., 1981, 10, 312.
B. V. Prelesnik, R. M. Herak, I. Micovic, and B. Jelenkovic, Acra Crystallogr., Ser. B, 1981,
37, 1793.
H. Fuhrer, L. Lorenc, V. PavloviC, G. Rihs, G. Rist, J. Kalvoda, and M. Lj. Mihailovid,
Helv. Chim. Acta, 1981, 64, 703.
A. DAndrea, W. Fedeli, E. Giglio, F. Mazza, and N. V. Pavel, Acta Crystallogr., Ser. B,
1981, 37, 368.
A. Messerschmidt, E. Hoehne, and B. Streckenbach, Cryst. Struct. Commun., 1981, 10, 141.
A. Messerschmidt, E. Hoehne, and R. Megges, Cryst. Struct. Commun., 1981, 10, 149.
Physical Methods
273
2 N.M.R. Spectroscopy
lH Spectra.-The total analysis of the IH n.m.r. spectrum of 11p-hydroxyprogesterone, reported briefly last year,42has now been described in full.43This is a
further illustration of the value of computer-controlled use of a 400 MHz spectrometer to obtain two-dimensional J spectra, and n.0.e. difference and decoupling
difference spectra, which provided all the lH chemical shifts and virtually all
geminal and vicinal coupling constants. Comparisons with the previously reported
findingP for 1-dehydrotestosterone acetate represent the first step in a correlation
of detailed n.m.r. and structural parameters which promises to have widespread
application in future studies on steroidal and terpenoid compounds. 220 MHz
spectra permit quantitative estimation of C-24 epimeric mixtures of 24-alkyl
A combination of procedures using IH n.m.r. allowed assignment of configurations to a series of 15,16,17-trisubstituted oestra- 1,3,5(lO)-triene~.~~
Coupling
constants between ring D protons were not alone sufficient, but were augmented
by chemical shift data, including the downfield shifts of methine proton signals on
reaction of hydroxy-groups with trichloroacetyl isocyanate. Spectra of protonated
forms of androst-4-en-3-ones, androsta-4,6-dien-3-one, and 17,17-dimethy1-18norandrosta-4,6,8(14)-trien-3-one in 80 % H2S04 indicate the presence of the
0-protonated species. The trienone was the only one of the compounds to undergo
vinyl proton exchange in 80% D2S04.46The presence of a 5-hydroxy or particularly a 5-acetoxy substituent in either 5a- or 5p-steroids causes deshielding
effects on neighbouring protons (at C-4 and 6a) which can be useful in structural
assignments.4
Although aldosterone exists in the crystalline state in the 1 1p, 18: 18,2O-diepoxy20-hydroxy form (7), and in solution as a mixture containing both the diepoxy
form (7) and the 11p, 18-hemiacetal-20-0x0 form (8) in substantial proportions,
n.m.r. and i.r. data show that 21-deoxy-3a,5p-tetrahydroaldosteroneexists in
solution essentially in the 11p, 18-hemiacetal-20-0x0form (9), with two epimers at
C-18 in the ratio 5 : 1.48 3a,5P-Tetrahydroaldosterone itself, however, is similar to
aldosterone in solution, where the n.m.r. spectrum indicates the presence of forms
(10) and (1 1) in ca. 1 : 1 ratio.49
s7
s8
38
E. Hoehne, A. Messerschmidt, B. Streckenbach, and I. Seidel, Cryst. Struct. Commun., 1981,
10,415.
40
41
4s
44
47
48
G. Reck, A. Messerschmidt, and R. Megges, Cryst. Struct. Commun., 1981, 10, 637.
E. Hoehne, A. Messerschmidt, R. Megges, and I. Seidel, Cryst. Struct. Commun., 1981,10,407.
Terpenoids and Steroids, ed. J. R. Hanson (Specialist Periodical Reports), Royal Society of
Chemistry, London, 1981, Vol. 11, p. 173.
L. D. Hall and J. K. M. Sanders, J. Org. Chem., 1981,46, 1132.
P. L. Chiu and G. W. Patterson, Lipids, 1981, 16, 203.
B. Schonecker, D. Tresselt, G. Schubert, and K. Ponsold, J . Prakt. Chem., 1981, 323, 207.
H. Takagi, M. Kokuryo, T. Miura, and M. Kimura, Bunseki Kugaku, 1981,30, 191.
M. Lj. MihailoviC, L. Lorenc,V. PavloviC, and H. Fuhrer, Helv. Chim. Actu, 1981, 64, 1032.
D. R. Crump, D. N. Kirk, and B. W. Miller, J. Chem. Soc., Perkin Trans. 1, 1980, 2597.
D. N. Kirk and B. W. Miller, J. Chem. SOC.,Perkin Trans. 1. 1980. 2818.
274
OH
P
(9) R
(10) R
=H
= OH
(11)
OH
The effect of the lanthanoid shift reagent [Ho(fod),] on spectra of sterol 3acetates is unusual. Induced shifts with this reagent are normally upfield, and the
C-19 and C-18 proton signals conform, although only weakly in the latter case.
The peculiarities lie in downfield shifts of the signals of side-chain methyl protons.
Moreover the C-26 and C-27 methyls are rendered non-equivalent by [Ho(fod)J,
and (24R)- and (24S)-24-methyl sterols are easily distinguished by the methyl
shifts.5oLanthanoid-induced shifts of methyl signals are reported for a series of
sterols with various ring and side-chain structures and substituents.61Jj2
13C Spectra.-An
n.m.r. technique53 for studying 13C-13C spin-spin coupling at
natural abundance offers a remarkable way of establishing the carbon-carbon
connectivities within an organic framework. Based upon the principle of doublequantum coherence, it suppresses the strong signals from isolated 13C nuclei and
reveals the weak 13C satellite spectrum. A complex pulse sequence (at 50 MHz)
and a two-dimensional Fourier transformation affords a spectrum with the 13C
satellite lines in the F, dimension and the corresponding double-quantum frequencies in the Fl dimension. Directly coupled 13C resonances generate the same
double-quantum frequency, and so can be recognized. Application of the technique
to 5a-androstane shows that it is capable of detecting even the complex connectivities within this four-ring system.63
Pulse sequences used to induce lH-13C polarization transfer (PT), with suitably
chosen delays (A) before data acquisition, provide a simple and reliable way of
separating 13C resonances according to the number of attached
In an
illustration for cholesterol, the seven CH carbons are displayed with A = (U)-l
bo
61
6s
6a
b4
T. Iida, T. Ishikawa, T. Tamura, and T. Matsumoto, Yukagaku, 1980, 29, 683.

T. Iida, Nihon Daigaku Kogakubu Kiyo Bunrui A, 1980,21, 227.
I. Takashi, Nihon Daigaku Kogakabu Kiyo Bunrui A , 1980, 21, 233.
A. Bax, R. Freeman, and T. A. Frenkiel, J. Am. Chem. SOC.,1981,103,2102.
D. M. Doddrell and D. T. Pegg, J . Am. Chem. SOC.,1980,102, 6388.
Physical Methods
275
= 3.8 ms. When A = 3(4J)-l = 5.7 ms, CH and CH3 signals appear in-phase and
CH2 signals 180" out-of-phase (inverted). Spin-echo Fourier transform (SEFT)
experiments which simplify 13C n.m.r. spectra to singlets offer another method for
distinguishing methyl, methylene, methine, and quaternary carbons which is
superior to off-resonance decoupling for complex molecules, illustrated by application to cholester01.~~
Cholesteryl acetate has been used as a model to demonstrate
the indirect measurement of proton relaxation rates by 'INEPT' polarization
transfer to directly bonded 13C nuclei;56direct measurement of proton Tl values is
impractical except for those few signals which are well separated from the crowded
methylene envelope.
Steroidal and other rigid alcohols have been used to derive a four-parameter
equation for the calculation of 13C chemical shifts due to substitution by the OH
Calculated 13C chemical shifts for all the likely saturated sterol sidechains with from seven to eleven carbon atoms have been tabulated and compared,
where possible, with published data.58 Good agreement is found in most cases,
with standard deviations of ca. 1 p.p.m. Only C-20, attached to the steroid nucleus,
showed serious deviations (ca. + 5 p.p.m.) from calculated values. The results
will be useful in future structural assignments of new sterols.
The aromatic ring of oestradiol or oestrone methyl ether readily forms a tricarbonyl chromium (0) complex in which the 13C signals from the aromatic ring
are shifted strongly upfield (by ca. 14-34 p.p.m.). Smaller upfield shifts for other
carbon atoms close to the aromatic ring (e.g. 2 p.p.m. for C-6) have been used to
settle uncertainties in the earlier literature concerning the assignments of individual
13C resonance^.^^ 13CN.m.r. spectra discriminate between A4- and A5-isomers of
spiro-3-steroidal ketone derivatives; thiazolidine formation results only in the
(3R)-isomer (12), whereas hemithioacetals are mixtures of the (3R)- and (3s)forms.60
(12) R = H or C0,Et
lSCN.m.r. data for a series of A5- and saturated 4,4-dimethyl-3-oxo-steroids and
related compounds reveal the distorting effect of A5-unsaturation on rings A and
B, and the effects of compression between the 4p- and C-19 methyl groups.61Longstanding uncertaintiess2 about the regioselectivity of the Beckmann, Schmidt, and
Baeyer-Villiger reactions of 3-keto-steroids and their derivatives have at last been
resolved by a 13C n.m.r. study of the reaction products and of the pure lactams or
sK
s7
68
IJO
D. W. Brown, T. T. Nakashima, and D. L. Rabenstein, J . Magn. Reson., 1981, 45, 302.

G. A. Morris, J. Magn. Reson., 1980, 41, 185.
V. Wray, Tetrahedron, 1981, 37, 777.
A. Kelecom, Bull. SOC.Chim. Belg., 1980, 89;343.
G. Pouskouleli, I. S. Butler, and J. P. Hickey, J. Znorg. Nucl. Chem., 1980, 42, 1659.
K. B. Sloan, N. Bodor, and R. J. Little, Tetrahedron, 1981,37, 3467.
S . Q. A. Rizvi and J. R. Williams, J . Org. Chem., 1981, 46, 1127.
Ref. 42, 1980, Vol. 10, p. 204.
276
lactones (5a- and 5

It is now clear that both possible migration products
are formed in varying proportions in each reaction. 13C N.m.r. spectra have been
assigned to a series of backbone-rearranged cholestanes (diacholestanes) by a
combination of SFORD, partially relaxed, and lanthanoid-shifted
Assignments for the 13(17)-ene (1 3) disagree with an earlier published set but seem
more reliably based. A combination of H two-dimensional J spectroscopy with
2H and 13Cn.m.r. has established the .2Hlabel distribution in the backbonerearranged isoholamine (14), which results from the reaction of holamine with
D,SO,, and has shown the rearrangement to occur mainly via a series of protonation-deprotonation steps.ss
(13)
(14) *Sites of 2H-labelling
Assignments are proposed for the 13C n.m.r. spectra of some natural and
synthetic hormonal steroids, including the acetates of cortisone, cortisol, prednisone, prednisolone and some of its derivatives [6a-Me; 9a-F, 16a-Me (dexamethasone) ; 9a-F, 16p-Me (betamethasone) ; 6a-F, 16a-Me (paramethasone)], and
a few miscellaneous compounds.6613C N.m.r. assignments have been revised for
p-sitosterol and its 3 - g l u ~ u r o n i d eand
~ ~ ~a reassignment of signals from ring F is
reported for (25S)-spiro~tans.~~
H and 13Cn.m.r., with n.0.e. experiments, have
established the structures (1 5 ) and (1 6) for gomphoside and afroside;69 other related cardenolide glycosides have also been studied. 70
(15) R
(16) R
H
OH
V. Dave, J. B. Stothers, and E. W. Warnhoff, Can. J . Chem., 1980, 58, 2666.

D. M. Tal, H. E. Gottlieb, C. Ben-Ari, and Y. Mazur, Tetrahedron, 1981, 37, 4331.
F. Frappier, W. E. Hull, and G. Lukacs, J . Org. Chem., 1981, 46, 4314.
M J. P. Hickey, I. S. Butler, and G. Pouskouleli, J. Magn. Reson., 1980, 38, 501.
O 7 1.-M. Chang, H. S . Yun, and K. Yamasaki, Saengyak Hukhoe Chi, 1981,12, 12.
an K. Tori, S . Seo, Y . Terui, J. Nishikawa, and F. Yasuda, Tetrahedron Lett., 1981, 22, 2405.
H. T. A. Cheung and T. R. Watson, J . Chem. SOC.,Perkin Trans. I , 1980,2162.
O H. T. A. Cheung, T. R. Watson, J. N . Seiber, and C. Nelson, J . Chem. SOC.,
Perkin Trans. 1,
Is
O4
1980, 2169.
Physical Methods
277
phytosterols 24-methylenecholesterol,
lSCN.m.r. data are reported for the A24(2s)
fucosterol, isofucosterol, and cycloeucalenol acetate, 71 for hecogenin acetate,
11-oxotigogenin, 6-methyldiosgenin acetate, botogenin, and other s a p o g e n i n ~ , ~ ~
for a series of 6,23-dihydroxylated sapogenins [e.g.solaspigenin (17), as triacetate],75
and for 29 withanolides and other polar c z s steroids.74
19F and 2H Spectra.-Substituent effects are reported on the lSF n.m.r. of sterol
trifluoroacetates.75 2HN.m.r. has been used to study the state of labelled cholesterol
in multibilayers of egg yolk lecithin containing digitonin. 78
3 Chiroptical Phenomena
The frequent observation of apparently bisignate character in the n+x* c.d.

bands in the region 300--400nm for steroidal 4-en-3-ones has generally been
ignored, but a new and detailed study now indicates that there are probably two
electronic transitions, singlet-triplet and singlet-singlet n+x*, respectively, which
sometimes result in overlapping but not coincident c.d. bands of opposite sign,
giving rise to the observed curve profile.77C.d. curves for (25R)- and (25S)-26hydroxycholesterol 3-acetate 26-p-bromobenzoates both show positive Cotton
effects at 240-244 nm due to the aromatic chromophore.78The chirality at C-25
cannot therefore be distinguished by this method. However, lanthanoid-induced
c.d., employing [Eu(fod)J, has been observed for the 25,26-diol system in 25,26dihydroxycholecalciferols,with signs corresponding to the configurations at C-25
[(25S), negative above 300 nm, positive below 300 nm; (25R) showed reversed
sign^].^ The exciton coupling principle has been extended to benzoates of allylic
alcohols, which show coupled transitions at ca. 230 nm (benzoate, Tc-+x*) and ca.
195 nm (olefin). The sign of the 230 nm c.d. band correlates with absolute configuration in the sense of Figure 1, confirmed by study of a series of steroidal
compounds belonging to this class.79
Negative
3
%OF-
(-) c.d. at ca. 230 nm

Figure 1 C.d. of allylic benzoates
pa
Positive
+Yo
H
O
(+)c.d. at ca. 230 nm
C.d. curves for the imines (Schiff bases) formed from some keto-steroids and
2-phenylethylamine, tyramine, or hexanamine show n+x* bands generally of the
same sign as those of the corresponding ketones, but near 235 nm.80Additional
A. G. McInnes, J. A. Walter, and J. L. C. Wright, Org. Mugn. Reson., 1980, 13, 302.
M. H. A. Elgamal, M. S. Bedour, and H. Duddeck, Indian J. Chem., Sect. B, 1980,19, 549.
A. K. Chakravarty, S. C. Pakrashi, and J. Uzawa, Cun. J. Chem., 1981,59, 1328.
'* H. E. Gottlieb and I. Kirson, Org. Mugn. Reson., 1981, 16, 20.
76 T. Iida, T. Tamura, and T. Matsumoto, Nihon Duiguku Kogukuba Kiyo Bunrui A , 1980,21,223.
T . Akiyama, S. Takagi, U. Sankawa, S. Inari, and H. Saito, Biochemistry, 1980, 19, 1904.
'I7 A. F. Beecham and D. C. Collins, Aust. J. Chem., 1980,33, 2189.
7 8 C.-Y. Byon, M. Gut, and V. Toome, J. Org. Chem., 1981, 46, 3901.
N. Haroda, J. Iwabuchi, Y. Yokota, and H. Uda, J . Am. Chem. SOC.,1981,103, 5590.
H. C. Price, D. G. Sawutz, T. E. Wagner, and C. Shewmaker, Tetrahedron, 1981, 37, 1679.
71
10
278
bands at 218-219 nm are attributed to the aromatic lLa transition for derivatives
of imines containing an aromatic group. Imines derived from testosterone or
oestrone showed additional c.d. features associated with the ap-unsaturation and
the aromatic ring A, respectively.
3 p-Acetoxyeti-5-enic esters have been used to resolve enantiomers of perhydroanthracenol (1 8)s1 and perhydrophenanthren-4-01( 19y2 as tricyclic systems for
study of the c.d. characteristics of the corresponding ketones.
(18)
(19)
C.d. and u.v.-visible spectra are reported for solutions of the antitumour triterpenoid tingenone in aqueous sodium deoxy~holate,~~
and c.d. curves have been
recorded for morphine and related alkaloids in cholesteric liquid crystals.84
4 Infrared Spectroscopy
Rather little attention is normally paid to the intensities of i.r. absorption bands
of steroids, but two papers now detail interesting variations in v(C=O) for primary,
secondary, and tertiary acetoxy-gro~ps,~~
and in v(C=O) and v(C=C) for variously
substituted progesterone derivatives.s5p861.r. absorption intensities of progesterone
derivatives have been studied with a Fourier-transform ~pectrometer.~~
5 Mass Spectrometry and Gas Chromatography-Mass Spectrometry

In a continued study of the mass spectrometric fragmentations of key classes of
steroids, 4,6-dien-3-ones and 1,4,6-trien-3-0nes have been shownss to undergo
characteristic rupture of ring B (Figure 2), accompanied in the case of 4,6-dienones
-2H
Figure 2 Mass spectral fragmentations of 4,6-dien-3-onesand 1,4,6-trien-3-ones
8a
8a
84
87
B. Alcaide and F. Fernandez, An. Quim., 1980, C76, 41.

B. Alcaide and F. Fernandez, J. Chem. SOC.,Perkin Trans. 1, 1980, 2250.
A. R. Campanelli, M. DAlagni, G. B. Marini Bettolo, and E. Giglio, Farmaco, Ed. Prat.,
1981, 36, 30.
J. M. Bowen, T. A. Crone, A. 0. Hermann, and N. Purdie, Anal. Chem., 1980,52, 2436.
G . Aruldhas, G. Jalsovszky, and S. Holly, Acta Chim. Acad. Sci. Hung., 1980, 104. 117.
S. Holly, G. Jalsovszky, and 0. Egyed, J. Mol. Struct., 1980, 60, 131.
G. Jalsovszky and 0. Egyed, Kem. Kod., 1980,54, 385.
F. J. Brown and C. Djerassi, J. Org. Chem., 1981, 46, 954.
Physical Methods
279
by the other cleavages illustrated. Hydrogen transfers during such processes have
been determined by specificdeuterium labelling. The very unusual loss of 44 mass
units from the 4,6-dienone involves expulsion of C2H40instead of the usual keten,
through a complex rearrangement which transfers the hydrogen atoms from C-4
and C-9 to the eliminated fragment.
5a-Androstane-7,17-dionesundergo a major and very strange mass spectral
fragmentation to give an ion with m/z = M - 47, irrespective of substitution in
~ ~
measurements indicate loss of CH302,and preliminary
ring A . High-resolution
experiments with deuteriated material (at 6, 6, 8P, 16, 16) indicate loss of CHD,02.
The nature of the fragmentation is as yet unknown. Trienes of the vitamin D
series show competition between two fragmentations with very similar energy
requirements. 5,7,10(19)-Trienes (20), irrespective of configuration, favour rupture
of the 7,8-bond, whereas 5(10),6,8-trienes(21) break preferentially across ring c.
(20)
(21)
In each case the resulting ions may fragment further. This very detailed study includes measurements of appearance energies of ions and ionization energies of
derivatives and isomers of vitamin D.90
Cleavage of side-chain trimethylsilyl ethers in the pregnane series is complicated
by Me,& exchange between oxygen atoms at C-17 and C-20.91Mass spectral data
are reportedg2for derivatives of 5?-pregnane-3a,17a,20a-trioI silylated selectively
at the 3- and 20-positions with either t-butyldimethylchlorosilane or t-butyltetramethylenechlorosilane and fully silylated by vigorous treatment with trimethylsilylimidazole. The mass spectral fragmentations of 3-methoxyoestra-l,3,
5(10)-trienes with hydroxy substitution at C-14, -15, -16, or -17 show distinctive
patterns, although the configuration of the hydroxy-group matters only at C-14 or
C-15,O3 Ions resulting from loss of water in the mass spectra of spirostan-3-01s
isomeric at C-3 and C-5 show characteristic relative intensities which can be
helpful in assigning configurations.94 The mass spectral fragmentation of 3a,5srcyclo-6-0x0-steroidsand other cyclopropyl ketones is a complex process.95 Selective
deuterium IabeIIing has shown that the [M - H20]+ ion from 3a,5-cyclo-5acholestan-6-one is derived from hydrogen atoms located at the 2P- and 9a-positions;
Bo
OS
J. E. Gurst and A. K. Schrock, J . Org. Chem., 1980,45, 4062.

Z. V. I. Zaretskii, Adv. MassSpectrom., 1980, 8, 590.
P. Vouros and D. J. Harvey, Biomed. Mass Spectrom., 1980, 7 , 217.
M. A. Quilliam and J. B. Westmore, Eur. J . Mass Spectrom. Biochem., Med. Environ. Res.,
1980, 1, 53.
oI
g6
W. Schade, W. Ihn, J. Vokoun, B. Schonecker, and G.Schubert, Steroid, 1980,36, 547.

G . Blunden, J. A. Jaffer, K. Jewers, and J. M. Robinson, Steroids, 1980, 36, 299.
A. Kasal and A. Trka, Collect. Czech. Chem. Commun., 1980, 45, 2985.
280
the detailed mechanism is not yet clear. Characteristic fragmentations are reported
for other 3,5-cyclocholestanyl derivatives (@-OH, -OMe, -OEt, -OBU'),~~
for the
corresponding cholesteryl
and for the ring B-hydroxylated 3P-acetoxy~-homo-5a-cholestanes.97 An interactive system of computer programs for the
elucidation of structures from mass spectral data is illustrated with reference to
some marine sterols. 98 The program generates all structural isomers compatible
with the data, and evaluates them in terms of biological plausibility.
Chemical Ionization Mass Spectrometry (CIMS).-Monohydroxylated cholesterols
are differentiated by h.p.1.c. and CIMS, with ammonia as reagent gas. Trimethylsilyl ethers of side-chain hydroxylated cholesterols fragment in CI mass spectra
with methane to give [C,H,,OSiMe,]+ ions characteristic of the site of hydroxyl a t i ~ nCIMS
. ~ ~ with ammonia as the reagent gas proved highly efficient for producing [ M + NH,]+ ions as base peaks from a series of methyl ester-acetate
derivatives of bile acids. Minor peaks permitted selective detection of 3-keto or
unsaturated bile acids.looAnother paper lol describes the application of CIMS to
the identification of side-chain hydroxylated cholesterols, sterol esters, bile acids,
and even underivatized steroid glycosides, and a CIMS study of (20s)-protopanaxadiol (22) and (20s)-protopanaxatriol (23) is reported.lo2
(22) R = H
(23) R = a-OH
Further
of the application of negative ion CIMS to steroids have
shown that use of Freon 12 (CF,Cl,) as reagent gas provides very satisfactory
[A4 + Cl]- ions, even from polyfunctional compounds like prednisolone which are
prone to fragmentation. Bile acid chlorides, with CH, as reagent gas, gave
[ M + OH]- peaks (doublets, containing chlorine).lo4Negative ion CI (with OH-)
provides mass spectra of underivatized steroid glucuronides (RO-gluc), showing
abundant [ M - HI- and [ROI- ions. lo5
Gas Chromatography-Mass Spectrometry (g.c.-m.s.).-Syntheses
of twenty
different steroids (oestrogens, androgens, progesterone, and corticosteroids and
their metabolites) with from two to four deuterium atoms per molecule have
F. J. Brown, I. J. Massey, and C. Djerassi, Can. J. Chem., 1980, 58, 2592.
F. Turecek and L. Kohout, Collect. Czech. Chem. Commun., 1980, 45, 2433.
N. A. B. Gray, A. Buchs, D. H. Smith, and C. Djerassi, Helv.Chim. Acta, 1981, 64, 458.
Y.Y.Lin, C.-E. Low, and L. L. Smith, J . Steroid Biochem., 1981, 14, 563.
loo B. R. DeMark and P. D. Klein, J . Lipid Res., 1981, 22, 166.
lol Y . Y . Lin, Lipids, 1980, 15, 756.
Ioa M. Desage, M. Becchi, M. Trouilloud, and J. Raymaud, Planta Med., 1980, 39, 189.
Io3 H. Fujiwara and A. K. Bose, Pract. Spectrosc., 1980, 3, 329.
lo4 H. Fujiwara and A. K. Bose, Pract. Spectrosc., 1980, 3, 373.
Io6 A. P. Bruins, Biomed. Mass Spectrom., 1981, 8, 31.
O7
Physical Methods
28 1
provided internal standards for isotope-dilution g.c.-m.s. studies. The labelled

steroids were isotopically stable to the conditions of derivatizationfor g.c. purposes
and to incubation in plasma. It was noted that more than four deuterium atoms
may result in decreased g.c. retention times, sufficient to broaden or even to split
peaks.loGBile acids are efficiently analysed (g.c.-m.s.) as their hexafluoroisopropyl
ester trifluoroacetates, which are superior to heptafluorobutyrates.lo7 Selective
oxidation of 3 p-hydroxy-5a- and 3 p-hydroxy-A5-steroIds by cholesterol oxidase
has been adapted as a method for improving the analysis of steroid mixtures by
g.c.-m.s., when g.c. peaks happen to overlap.1os Characteristic retention increments are quoted for a series of sterol-keto-steroid pairs. Some further applications of the formation of cyclic methylboronates from diols (20,21 - and 20,22-)
are also described.losA further paperlog has appeared on the identification of
sterols and bile acids by computerized g.c.-m.s., using fragment ion current
chromatograms.l10 Biomedical applications of g.c.-m.s. to the study of steroid
hormones have been reviewed (208 references).ll*
6 High-performance Liquid Chromatography (h.p.1.c.) and other
Chromatographic Methods
A review of h.p.1.c. of steroid hormones traces the history of the subject, and
describes methods for h.p.1.c. analyses of the main classes of steroids in biological
fluids and pharmaceuticals.112
H.p.1.c. of adrenal 18-hydroxy-steroids (e.g. 18-hydroxycorticosterone, which
exists as the 18+20-hemiacetal) is complicated by their labile nature. Normal
handling, without special precautions, may result in the formation of 20-alkoxyderivatives, dehydration products, or dimers. Procedures are now described113for
the extraction and reversed-phase h.p.1.c. of these compounds from biological
sources without the appearance of artefacts. H.p.1.c. separations of aldosterone
and its metabolites from biological sources have distinguished between known
derivatives and some unidentified reduced and polar metabolites, which may have
physiological significance.l14 H.p.1.c. separations and retention data are reported
for all the isomeric reduced metabolites of progesterone, where combinations of
normal and reversed-phase columns can resolve complex mixtures of biological
origix~,l~~*ll~
and for the steroid hormones in adrenal and testicular
An extensive review (155 references) of the separation and determination of D
vitamins by h.p.1.c. includes discussion of the problem of instability, and a detailed
lo6
L.Dehennin, A. Reiffsteck, and R. Scholler, Biomed. Muss Spectrom., 1980, 7 , 493.
R. Edenharder and J. Slemr, J. Chromutogr., 1981, 222, 1.

C. J. W.Brooks, W. J. Cole, H. B. Mclntyre, and A. G. Smith, Lipids,1980,15,745.
loo W.H.Elliott, Lipids, 1980, 15, 764.
Ref. 42, 1981, Vol. 11, p. 183.
n1 H. Adlercreutz, Adv. Muss Spectrom., 1980, 8B, 1165.
F. A. Fitzpatrick, Adv. Chromutogr., 1978, 16, 37.
113 M. J. OHare, E. C. Nice, and M. Capp, J. Chromutogr,, 1980, 198, 23.
D. J. Morris and R. Rsai, Adv. Chromutogr., 1981, 19, 261; D. J. Morris, Endocrine Rev.,
1981,2,234.
116 J.-T. Lin, E. Heftmann, and I. R. Hunter, J. Chromutogr., 1980, 190, 169.
R. H. Purdy, C. K. Durocher, P. H. Moore, and R. N. Rao, Chromatogr. Sci., 1981, 16, 81.
11 M. J. OHare and E. C. Nice, in Steroid Analysis by H.p.l.c., ed. M. P. Kautsky, Dekker,
New York, 1981, pp. 277-321.
lo8
282
account of chromatographic systems for the separation of vitamins D, and D,,

their precursors, isomers, and metabolites.ll8 The sensitivity of U.V. detection of
the vitamins D (20) and their metabolites during h.p.1.c. is improved two-fold
by prior HC1-catalysed isomerization to their isotachysterol derivatives (24).lls
Ternary solvent systems are recommended for the h.p.1.c. resolution of hydroxylated metabolites of vitamins Dz and D3,lZ0and in general for the separation of
polar steroid hormones on reversed-phase h.p.1.c. systems when binary solvent
mixtures prove unsatisfactory.lZ1
NMe,
(25) R = O-steroid
(24)
(26) R = CN
Practical problems of chemical reaction detection following elution from
h.p.1.c. columns have been examined with particular reference to the formation of
fluorescent derivatives of corticosteroids. Steroidal 4-en-3-ones are allowed to
react, for example, with isonicotinoylhydrazide, in an air-segmented tubular flow
system to minimize eluate mixing or band-broadening. Following de-aeration, the
solution then passes through a fluxescence detector, giving a system sensitive to
ca. 100 ng samples.122Dansyl derivatives have been used for h.p.1.c. of equine
oestrogens, with fluorescence detection ; the 17-keto-oestrogens were separated
after reduction with bor01iydride.l~~
4-Dimethylaminonaphthalene-1-carboxylates
(25), prepared from steroidal alcohols by reaction with the acyl cyanide (26), may
be used for h.p.1.c. with absorbance and fluorescence detectors.lZ4
H.p.1.c. procedures are described for the separation of cardiac glycosides,125
metabolites of ecdysone,126and solanum and veratrum alka10ids.l~~
Sterol intermediates in cholesterol biosynthesis have been resolved by a threestep chromatographic procedure.128A detailed study of reversed-phase thin-layer
chromatography of a wide variety of steroids (on silanized silica gel) includes a
correlation of ARM values of substituents with hydrophobicity
R.Vanhaelen-Fastre and M. Vanhaelen, Chromatogr. Sci., 1981, 16, 173.
D.A. Seamark, D. J. H. Trafford, P. G. Hiscocks, and H. L. J. Makin, J . Chromatogr., 1980,
Ile
llB
197,271.
G.Jones, J . Chromatogr., 1980, 221, 27.
121 G. J.-L. Lee, R. M. K. Carlson, and S. Kushinsky, J . Chromatogr., 1981, 212, 108.
12% E. Reh and G. Schwedt, Fresenius' 2. Anal. Chem., 1980,303, 117; G. Schwedt and E. Reh,
120
Chromatographia, 1981, 14, 249, 317.
R. W. Roos and T. Medwick, J . Chromatogr. Sci., 1980, 18, 626.

12* J. Goto, S. Komatsu, N. Goto, and T. Nambara, Chem. Pharm. Bull., 1981, 29,899.
lZ5 V. Y. Davydov, M. Elizalde Gonzalez, and A. V. Kiselev, J. Chromatogr., 1981, 204, 293.
lZ8
R.Lafont, P.Beydon, G . Somme-Martin, and C. Blais, Steroids, 1980, 36, 185.
12' I. R. Hunter, M. K. Walden, and E. Heftmann, J . Chromatogr., 1980, 198,363.
lZ8 E.Hansbury and T. J. Scallen, J . Lipid. Res, 1980, 21, 921.
12@ J. Draffehn, B. Schonecker, and K. Ponsold, J . Chromatogr., 1981, 205, 113.
123
Physical Methods
283
Centrifugal thin-layer chromatography is claimed to provide a fast and efficient

separation of ginsenosides and other natural products.13*Olefinic insect pheromones are separated efficiently on glass capillary columns coated with the correct
film thickness of cholesteryl cinnamate in the liquid crystalline phase.131 Methoxyamine has a catalytic effect in the silylation of the hindered hydroxy-group
of 17phydroxy- 17a-methylandrosta-1,4-dien-3-one with common silylating reagents.132
7 Immunoassays
Those immunoassays which depend upon a tracer attached by a bridge to the
steroid have a potentially serious disadvantage compared with the use of the
tritium-labelled steroid as tracer. Antibodies produced in response to a steroidprotein complex (antigen) may recognize not only the steroid but also the bridge
by which the steroid-protein linkage is achieved. If the same bridging group links
the steroid to the moiety which ultimately acts as tracer, competition between the
natural steroid and the steroid-tracer complex for antibody binding may excessively favour the tracer if the antibody recognizes the bridge as well as the steroid.
The resulting preferential binding of the tracer complex by the antibody reduces the
sensitivity of the immunoassay.
Bridge recognition has proved to be a problem when the tracer is the y-emitting
p251]iodotyrosinelinked to the steroid via a succinoyl bridge. For a [lZ5I]-based
assay of androstenedione, using an antibody to the ester-linked 19-succinoyl-BSA
complex (27), bridge recognition has been reduced to produce a sensitive assay by
employing an ether-linked bridge from C-19 to tyramine as the iodinated label
(28)?%
NH-BSA
(27)
(28)
The principle of bridge heterology has been applied also to cortisol enzymeimmunoassay, by linking !3-galactosidase through a variety of bridges to C-4
(29).134A shorter bridge than that used for the antigen gave improved sensitivity,
but a longer bridge gave no advantage.
Antibodies with high specificity for 4-hydroxy-oestrogens have been obtained
by use of a 17-(O-carboxymethyl)oxime-BSA conjugate as antigen; the same hapten
combined with [1251]iodohistaminewas employed as radioactive tracer.135Antisera
K. Hostettmann, K. M. Hostettmann, and 0. Sticher, J. Chromatogr., 1980, 202, 154.
R. R. Heath, J. R. Jordan, and P. E. Sonnet, J . High Resolut. Chromatogr. Chromatogr.
Commun., 1981, 4, 328.
13a A. B. Benko and V. Mann, Anal. Lett., 1980, 13, 735.
G. D. Nordblom, R. Webb, R. E. Counsell, and B. G. England, Steroids, 1981,38, 161.
13* H. Hosoda, N. Kawamura, and T. Nambara, Chem. Pharm. Bull., 1981, 29, 1969.
lab D. Berg and E. Kuss, 2. Physiol. Chem., 1980, 361, 1743.
13*
284

CH,OH
---OH
(29)
R = SCH,CO,H, or SCH,CH,CO,H, or SCH,CH,0COCH,CH,C02H,
or OCOCH,CH,CO,H
for testosterone and 17P-hydroxy-5a-androstan-3-one(DHT) having low crossreactivities have been obtained by pretreatment of mice with the cross-reacting
steroid coupled via a 15~-carboxymethylmercapto
bridge to a copolymer of Dglutamic acid and D-lysine, before immunization with testosterone-protein or
DHT-protein complex in the usual
Radioimmunoassay of solasodine and
related plant alkaloids is rep0~ted.l~
New enzyme-immunoassays include use of the P-galactosidase conjugate of
1 1a-hemisuccinoyloxyprogesteroneas tracer for a sensitive assay of progesterone
in bovine milk,13*one for the synthetic anti-inflammatory steroid betamethasone,
using the 3-(O-carboxymethyl)oxime-~-~-galactosidase
conjugate as labelled
antigen and 4-methylumbelliferyl-~-D-galactoside
as a fluorescent tracer,139 and
a method for the quantification of d i g o ~ i n . l ~ ~
A fluorescence-quenching immunoassay for cortisol, based upon the use of a
tracer comprising fluorescein linked to the steroid via a 21-amino-group, claims a
good correlation with radioimmunoassay results. Separation of free and bound
fractions is unnecessary with this
Chemiluminescence-labelling has been applied to the immunoassay of oestriol
16a-glucuronide by synthesis of the N-aminobutyl-N-ethylisoluminolderivative
(30), which emits light when oxidized with H,O,-microperoxidase. Binding of the
conjugate (30) to an antibody for the steroid enhances light emission. Competitive
K. Tateishi, T. Hamaoka, C. Hayashi, J. Goto, S. Ikegawa, and T. Nambara, Steroids, 1980,

36, 283.
13 E. W. Weiler, H. Krueger, and M. H. Zenk, Planta Med., 1980, 39, 112.
M. J . Sauer, J. A. Foulkes, and A. D. Cookson, Steroids, 1981, 38, 45.
13@ G. Kominami, A. Yamauchi, S. Ishihara, and M. Kono, Steroids, 1981, 37, 303.
140 N. Monji, H. Ali, and A. Castro, Experientiu, 1980, 36, 1141.
lol Y. Kobayashi, N. Tsubota, K. Miyai, and F. Watanabe, Steroids, 1980, 36, 177.
13
Physical Methods
285
binding of oestriol 16a-glucuronide itself by the antibody inhibits the enhancement of emission, providing the basis of a very sensitive assay.142
A direct chemiluminescence assay for urinary pregnanediol 3-glucuronide
employs the isoluminol conjugate (3 1) as tracer, with monoclonal antibodies.
Specificity is excellent, the assay being sensitive to 30 pg.lP3A solid-phase chemiluminescence assay for plasma progesterone uses as tracer the isoluminol conjugate
(32) derived from 1 1a-hydroxyproge~terone.~~~
\)...OH
(32)
Hydroxy-steroid dehydrogenases co-immobilized on Sepharose 4B with
NADH : FMN oxidoreductase and luciferase provide light-emission assays for
picomole levels of androsterone or testo~terone.'~~
8 Miscellaneous
The nitroxide (33) closely resembles cholesterol in its physical and biological
properties, and has been used as a spin-labelled analogue of cholesterol to investigate cholesterol-protein interactions in human high-density 1ip0protein.l~~
The
fluorescent cholesterol analogue N-(7-nitrobenz-2-oxa-1,3-diazole)-22-amino-23,
24-dinorchol-5-en-3p-01(34) has been used as a substrate for lecithin : cholesterol
F. Kohen, J. B. Kim, G. Barnard, and H. R. Lindner, Steroids, 1980, 36, 405.
Z. Eshhar, J. B. Kim, G. Barnard, W. P. Collins, S. Gilad, H. R. Lindner, and F. Kohen,
Steroids, 1981, 38, 89.
14* F. Kohen, J. B. Kim, H. R. Lindner, and W. P. Collins, Steroids, 1981, 38, 73.
J. Ford and M. DeLuca, Anal. Biochem., 1981, 110, 43.
u6 J. F. W. Keana, T. Tamura, D. A. McMillen, and P. C. Jost, J . Am. Chem. SOC.,1981, 103,
lQB
4904.
286
(33)
(34)
acyltransferase, and as its linoleate ester was incorporated into low-density lipop r o t e i n ~ .A
~ ~fluorimetric
'
assay for ecdysteroids is sensitive to 10-l' rn01e.l~~
Esters of oestradiol and other steroids with ferrocenecarboxylic acid149have
been converted into [103R~]ruthenocenecarboxylatesby exchange with [lo3Ru]RuC13,150 for use as y-emitting tracers in organ-affinity s t ~ d i e s . l ~ ~
Improved
J~l
yields were subsequently obtained by esterifying the steroid with [103R~]ruthenocenecarboxylic acid chloride obtained via metal exchange in o-chlorobenzoylferr0~ene.I~~
lo3Ruprovides a useful alternative to 1251as a y-radioactive tracer.
The use of tetrazolium salts in the analysis of corticosteroids and other pharmaceuticals has been reviewed.153Polarographic study of cholesterol, 7-dehydrocholesterol, Vitamin D3,and related compounds has revealed differences in oxidation potentials which were correlated with molecular shape.154The measured
dipole moment of cholesterol in toluene (1.55 D at 40 "C) increases at lower
temperatures owing to molecular aggregati~n.'~~
Equilibration of the diastereoisomers of cholestane (Pt-C at 600 "C) has shown the most stable to be (20R)and (20S)-5a,14p, 17P-ch01estanes.l~~
A review of the use of torsion angle notation
to describe stereochemical processes in cyclic molecules includes some steroid
exam~1es.l~~
An interactive computer programme (SCRIPT) which can provide
conformers and their relative energies has been applied to steroid molecules by
drawing their formulae on a cathode ray tube.15*
The relationship between crystal packing and liquid crystalline ordering has been
discussed for cholesteryl n-alkanoates with between two and eighteen carbon
atoms in the acyl group.159The mesomorphic transition temperatures of cholesteryl
oleate, linoleate, and linolenate are pressure-dependent.160The thermal stabilities
147
14*
lSo
151
15a
153
150
168
I. F. Craig, D. P. Via, W. W. Mantulin, H. J. Pownall, A. M. Gott, jun., and L. C . Smith,

J . Lipid Res., 1981, 22, 687.
J. Koolman, Insect Biochem., 1980, 10, 381.
K. Hoffmann, B. Riesselmann, and M. Wenzel, Liebigs Ann. Chem., 1980, 8, 1181.
B. Riesselmann and M. Wenzel, Hoppe-Seyler's Z . Physiol. Chem., 1977, 358, 1353.
M. Wenzel and K. Hoffmann, Naturwissenschaften, 1979, 66, 313.
K. Hoffmann, B. Riesselmann, and M. Wenzel, J . Labelled Compd. Radiopharm., 1980, 17, 421.
G. E. Veeman, Pharm. Weekbl., 1981, 116, 109.
M. Wilk and K . Schmitt, Z . Naturforsch., Teil B, 1980, 35, 1496.
L. L. Burshtein, T. P. Stepanova, and A. V. Purkina, Zh. Fiz. Khim., 1980, 54, 1493.
S . D. Pustil'nikova, N. N. Abryutina, G . P. Kayukova, and A. A. Petrov, Neftekhirniya, 1980,
20, 26.
lS7
E. Toromanoff, Tetrahedron, 1980, 36, 2809.

N. C. Cohen, P. Colin, and G . Lemoine, Tetrahedron, 1981, 37, 1711.
P. Sawzik and B. M. Craven, Liq. Cryst. Proc. Znt. Cunf., Pittsburgh, U.S.A., 1979 (Pub].
1980), 171.
ld0 M.
Nakahara, K. Maeda, and J. Osugi, Bull. Chem. Sac. Jpn., 1980, 53, 2499.
Physical Methods
287
of the cholesteric mesophase of esters of cholesterol with a series of m- and p substituted benzoic acids (PhXC6H,C02H) depend upon the nature of the linkage
(X), and decrease in the order CO > 0 > S > CH2.161A further study has been
reported16aon the blue phases163of cholesteryl nonanoate and myristate.
A bibliography, Fifty years of oestrogen analysis, is available in rni~rofiche.16~
la
M. Koden, S. Takenaka, and S. Kusabayashi, Chem. Lett., 1980, 5,471.
m2
S. Meiboom and M. Sammon, Phys. Rev. A, 1981, 24,468.
le3
Ref. 42, 1980, Vol. 10, p. 211; 1981, Vol. 11, p. 185.
R. W. A. Oliver, C. T. Brooks, and J. E. Sugden, Biological Materials Analysis Unit, University of Salford M5 4WT, U.K., 1980.
le4
2
Steroid Reactions and Partial Syntheses
BY 6. A. MARPLES
SECTION A: Steroid Reactions
1 General
Reviews on the use of DMSO in synthesis,l functionalized polymers as heterogeneous reagents,2 methods of fl~orination,~
and the application of the torsion
angle notation in 5-, 6 ,and 7-membered rings4 all contain steroidal examples.
2 Alcohols and Carboxylic Acids and their Derivatives, Halides, and
Epoxides
Solvolysis, Substitution, Elimination, and Reduction.-Studies on the solvolysis of
3~-tosyloxy-5,10-secocholest-l(
lO)-en-5-ones have been reported5 and are complementary to those reported earlier6 on similar compounds. Considerable double bond
participation was observed for the 2-3a-compound (I), the E-3a-compound (2),
&
TsO
A. J. Mancuso and D. Swern, Synthesis, 1981, 165.

A. Akelah, Synthesis, 1981, 413.
M. R. C, Gerstenberger and A. Haas, Angew. Chem., Int. Ed. Engl., 1981, 20, 647.
E. Toromanoff, Tetrahedron, 1980, 36,2809.
L. Lorenc, M. J. GBsiC, I. JuraniC, M. Dabovib, and M. Lj. Mihailovib, J. Chem. SOC.,
Perkin
Trans. 2, 1980, 1356.
See 'Terpenoids and Steroids', ed. J. R. Hanson (Specialist Periodical Reports) The Royal
Society of Chemistry, London, 1982, Vol. 11, p. 187.
288
289
and the E-3p-compound (3) but not for the 2-3p-compound (4). A study' of the
conformations of esters of 2-3E-hydroxy-5,lO-secocholest1(lO)-en5-ones and the
related 3,5-diketone is also relevant to this work.
Diethylazodicarboxylate-Ph,P mediated reactions have been reviewed and
steroid substitution reactions were included.* Reactions of 3-O-acetyldigitoxigenin
with SF4-KF gave the 14~-fluoro-derivative. Sa-Cholestan-3p-01 was converted
into 3a-cyano-cholestanol by treatment with NaCN-Me3SiCI (2 equivalents) and
NaI (catalyst) in DMF-MeCN.1 Acetolyses of 4-, 6a-, and 6p-bromocholest-4-en3-ones catalysed by AgOAc gave the 6-acetoxy-compounds in contrast to similar
reactions with KOAc where 2- and 4-acetoxy-compounds may result.ll In those
cases where the S,l mechanism operated the attack on the mesomeric cation at C-6
was largely stereoelectronically controlled 6p. Controlled alkaline hydrolysis of
16a-bromo- 17-keto-steroids with NaOH in aqueous pyridine gave the 16a-hydroxy17-keto-compounds and no rearranged ketols.12J3 Studies with l8O-1abelled base
suggested that epimerization of the 16~-bromineis followed by its direct displacement,12 21-Mesyloxy-20-keto-17-hydroxy-compounds were reported to react
smoothly with thiolate anions [e.g. thiolacetate and O-ethylxanthate] in contrast
with other nitrogen and oxygen nu~leophiles.~~
The 17-hydroxy-group appeared to
catalyse the reactions.
Calculations suggested that the preferred elimination of 3-substituted androstanes to give A2- rather than A3-compounds could not be explained alone by
differences in calculated heats of formation. Differences in the energies of the
respective transition states appeared to be irn~0rtant.l~
Dehydration of the cyclobutanol (5) gave largely the exo-alkene (7) but the tetradeuterio-compound (6)
(9)
H. Fuhrer, L. Lorenc, V. PavloviC, G . Rihs, G. Rist, J. Kalvoda, and M. Lj. MihailoviC,
Helv. Chim. Acta, 1981, 64, 703.
0. Mitsunobo, Synthesis, 1981, 1.
A. Haas and D. Kortmann, Chem. Ber., 1981,114,1176.
l o R. Davis and K. G. Untch, J. Org. Chem., 1981, 46, 2985.
l1 T. Koga and Y . Nogami, Tetrahedron Lett., 1981, 22, 3075.
l2 M. Numazawa and Y . Osawa, J. Am. Chem. SOC.,1980,102, 5403.
l3 M. Numazawa and Y . Osawa, Steroidr, 1981,38, 149.
l4 S. S. Simons, M. Pons, and D. F. Johnson, J . Org. Chem., 1980, 45, 3084.
l5 W. Gschwendtner, V. Hoppen, and H. J. Schneider, J. Chem. Res. (S), 1981, 96.
290
gavel6 a greater proportion of the endo-alkene (8) which was used to prepare 18oxoprogesterone (9). Hydrogenolysis of 3- and 24-fluoro-compounds was effected
with potassium and dicyclohexyl-18-crown-6 in toluene or dig1yme.l'
Epoxide Ring 0pening.-A detailed study has been reported for the Li-NH3
reductions of la,2a-epo~y-h~~~-3-keto-steroids.~~
Reproducible and optimum
yields of the 1a,3~-dihydroxy-A5-compounds
were obtained by using an initial
reduction with a stoicheiometric quantity of Li-NH, followed by protonation with
NH4Cl and repeated alternating treatment with NH4C1 and Li. Diaxial chlorohydrins were formed from the reactions of 5,6-epoxy-cholestaneswith trimethylsilyl
ch10ride.l~The participation of 19-substituents in the HBr- and HC104- catalysed
cleavages of 5a,6a-epoxycholestanes was compared20with similar reactions of the
3 P-acetoxy-derivati~es,~~
The absence of the 3P-acetoxy-group was significant in
that in the reaction of the 19-acetoxy-5a,6a-epoxide(10) with HBr, the participation
(10) R
AC
(11) R = Me
of the 19-acetoxy-group was only partially rather than fully suppressed. In the
reaction of the 19-methoxy-5a,6a-epoxide(1 1) with HBr, no participation of the
methoxy-group was observed and only the normal bromohydrin was formed. A
study of similar reactions of 3cc,4a- and 4a,5a-epoxycholestanes was reported.22
The effects of a-acetoxy- and cc-hydroxy-groups on the aqueous HCIO,-catalysed
ring opening were reported for the l-oxo-4,5-epoxycholest-2-enes(12) and the
(12) R'=
R'
R'
R'
R'
=
=
=
=
R2= H
OH, R2= H
H, R2= OH
OAC, R2= H
(13) R
H, Me, or Ac
H, R2= OAC
3p,6p-disubstituted-4,5-epoxycholestanes(1 3).23 In the former, it was suggested
that the polar group repulsions in the transition state were important and it was
M. Mujano, J. Org. Chem., 1981, 46, 1854.
T. Ohsawa, T. Takagaki, A. Haneda, and T. Oishi, Tetrahedron Lett., 1981, 22, 2583.
A. Fiirst, L. Labler, and W. Meier, Helv. Chim. Actu, 1981, 64, 1870.
l o M. Husain and N. H. Khan, Synth. Commun., 1981, 11, 185.
2o P. KoEovsky and V. Cerny, Collect. Czech. Chem. Commun., 1980, 45, 3190.
21 See 'Terpenoids and Steroids' ed. J. R. Hanson (Specialist Periodical Reports), The Royal
Society of Chemistry, London, 1981, Vol. 10, p. 216.
22 P. KoEovsky and V. terny, Collect. Czech. Chem. Commun., 1980, 45, 3199.
M. Ishiguro, H. Saito, Y. Hirano, and N. Ikekawa, f. Chem. Soc., Perkin Trans. I , 1980,2503.
l6
l7
29 1
observed that the 6p-acetoxy-group prevented cleavage of the 4a,5a- and 4p,5pepoxides, while in the latter, the participation of the 3p- or 6p-acetoxy-groups
in the ring opening process was of particular importance and it was noted that the
4p,5@-epoxideswere unreactive.
Esters, Carboxylic Acids, and Ethers.-The rates of hydrolysis of 38- and 68acetoxy-4E,5E-epoxides and la-acetoxy-2p,3P-epoxides were observed to be
accelerated relative to those acetates not containing a neighbouring epoxide
Bile acid methyl esters were readily prepared from the carboxylic acids by
reaction with methanol in the presence of toluene-p-sulphonic
Bile acids were
readily converted into the amino-amides (14) by successive reaction with BulN-
Bu'OCOCl and 1,2-diamin0ethane.~~

A number of side chain keto-steroids were
obtained by reactions of the carboxylic acid chlorides with organomanganous
iodides and the reactions are exemplified by the conversion of the acid chloride (15)
into the 24-keto-compound (16) using isobutylmanganous iodide.27The 16a,1 7 ~ (alkoxymethy1enedioxy)-steroids (18) were prepared from the 16a-formyloxy-17ahydroxy-compounds (17) with acetals and P205.28The major product of thermal
decarboxylation of the 3,17-dioxo-4p,5p-epoxyandrostan-19-oic
acid (19) was the
hydroxy-enone (20).
Digitoxigenin 3-alkyl ethers were prepared by BF,.Et,O-catalysed alkylation of
digitoxigenin with diazoalkanes, AgBF,-assisted solvolysis of 3-desoxy-3a-iododigitoxigenin, and MCPBA-induced oxidative solvolytic displacement on the
3-desoxy-3a-iodo-compound in alcohols.30
M. Ishiguro, H. Saito, and N. Ikekawa, J. Chem. SOC.Perkin Trans. 1 , 1980, 2507.

B. Dayal, J. Speek, E. Bagan, G. S. Tint, and G. Salen, Sferoids, 1981, 37, 239.
A. Hill, P. E. Ross, and I. A. D. Bouchier, Steroids, 1981, 37, 393.
G. Cahiez, Tetrahedron Lett., 1981, 22, 1239.
J.-C. Hilscher, Chem. Ber., 1981, 114, 389.
2B H. Mastalerz and P. Morand, J. Org. Chem., 1981, 46, 1206.
30 R.Greenhouse and J. M. Muchowski, Can. J. Chem., 1981,59, 1025.
25
292
OR
{gH
OR
---0COH
(18) n
1 or 3
Treatment of oestrone with tetraphenylbismuth monotrifluoroacetate gave

oestrone phenyl ether and exemplified, in part, a new procedure for aryl ether
f ~ r m a t i o nA
. ~ detailed
~
study was reported of the formation of benzyl ethers by
sequential reaction of alcohols with chloro(phenylmethy1ene)dimethylammonium
chloride and sodium hydrogen telluride.32 Steroidal alcohols, inter alia, were
converted into hydrolytically stable silyl ethers by reaction with Bu'Me,SiI or
Bu'PhJ which were generated in situ from the selenosilane and iodine.33 The
5cc-hydroxycholestane (2 1) was protected in this way.
3 Unsaturated Compounds
Electrophilic Addition.-Reactions of androsta-3,5-dienes with MCPBA gave

complex mixtures the composition of which was dependent upon the level of
peracid used (1 or 2 equivalents). Diepoxides were isolated in low yield only when
2 equivalents were used and in general products were derived from epoxide ring
opening.34 In a study of the structures of withanolides G,H,I,J,K, and U which
were all shown to possess the 14a-hydroxy-group, it was demonstrated that the
14a-hydroxy-group influenced the epoxidation of the 5,6-double bond.35Incorporation of ozonizable dyes as internal standards facilitated selective ozonization of
31
52
D. H. R. Barton, J.-C. Blazejewski,B. Charpiot, and W. B. Motherwell,J. Chem. SOC.,Chem.

Commun., 1981, 503.
A. G . M. Barrett, R. W. Read, and D. H. R. Barton, J. Chem. SOC.,Perkin Trans. I , 1980,
2184.
a3
34
35
M. R. Detty and M.D . Seidler, J . Org. Chem., 1981, 46, 1283.

R. C. Cambie, C. M. Read, P. S. Rutledge, G . J. Walker, P. D. Woodgate, and J. R. Hanson,
J. Chem. SOC.,Perkin Trans. I , 1980, 2581.
I. Kirson and H. E. Gottlieb, J . Chem. Res. (S)., 1980, 338.
293
alkenes and 3-oxostigmasta-4,22-diene gave the aldehyde (22) in high yield using
solvent Red 23.36 Ozonolysis of hl6-20-oxopregnanes in CH2C12-lower alkanol
followed by reductive work-up with Me,S gave the novel 16P-alkoxy-17aahydroxy-D-homo-17-oxapregnanes (23).37
dcHo
o&OR /
(22)
(23) X = AcO, C1 or Br
Addition of HOBr to the 3p-acetoxy-oestr-4-ene (24) gave the 4p-acetoxy-5~bromo-3 p-hydroxy-compound (25) resulting from participation of the neighbouring
acetoxy-group.38 Equilibration of the major product (25) or its 3p-acetoxy-4phydroxy-isomer (26) led to a mixture containing largely the latter (ca. 85%).
Participation of 19-substituents in the additions of HOBr to A5-cholesteneswas
compared39 with that in the similar reactions of the 3p-a~etoxy-analogues~~
and the
AAJ
AcO
(25) R1= H, R2 = AC
(26) R1= Ac, R2 = H
(24)
AcO
&
HO
ir
(28)
@
Ho OR
(29) R
(30) R
36
s8
39
*O
=H
= AC
OH
(31)
(32)
T. Veysoglu, L. A. Mitscher, and J. K. Swayze, Synthesis, 1980, 807.

C. M. Cimarusti, P. G. Grabovitch, B. K. Toeplitz, R. K. Varma, and J. Z. Gougoutas, J. Org.
Chem., 1981,46,803.
D. F. Covey and V. D. Parikh, Steroids, 1980, 36, 451.
P. K&ovskY and V. Cernf, Collect. Czech. Chem. Commun., 1980, 45, 3023.
See reference 21, p. 218.
294
study was complementary to that reported for the 5a,6a-epo~ides.~~

The expected
6(0)n9nparticipation was observed for the 19-acetoxy-derivative(27) but in contrast
to the reaction in the 3p-acetoxy-series the 'abnormal' bromohydrin (28) was the
exclusive product. The formation of the bromohydrin (28) is a key step in the
synthesis of 19-functionalized-A4- and A3-cholestenes,41and the reactions of these
with HOBr were also reported to show participation of the 19-s~bstituents.~~
In similar studies, it was observed that addition of HOBr to thelop-vinylcholestanediol(29) gave the epimeric bromopyrans (3 1) whereas the 6@-acetoxy-analogue(30)
under similar conditions gave the spiro-ketone (32) in addition and in approximately equal yield.43
Other Addition Reactions.-A review of singlet oxygen used in organic synthesis
contained some steroidal examples.44Ergosteryl acetate was reported to react with
NOCN which was cleanly generated by thermolysis of the cycloadduct of 9,lOdimethylanthracene and NOCN. Both regioisomers (33) and (34) were 0btained.4~
CN
(33)
(34)
A number of hindered steroidal alkenes were successfully hydrogenated using

[Ir(cod)py(PCy,)]PF, as homogeneous catalyst.46Ketones, C-halogen bonds, and
cyclopropane rings were unreactive. Platinum-catalysed hydrogenations of the
12-oxo-5@-chol-9(
11)-enates (35) have been studied and deoxygenation at C-12 and
(35) R = a-OH, H
R = a-OAc, H
R=0
R=
H
2
R = @-OH,H
at C-3 (for the 3-0x0-derivative) was noted particularly in those reactions in which
significant saturation of the double bond was a~hieved.~'
Other Reactions of Unsaturated Steroids.-Allylic alkylations catalysed by palladium have been reviewed and steroid examples are i n c o r p ~ r a t e d .The
~ ~ full
41
42
43
44
45
46
47
4B
P. KoEovsky, Collect. Czech. Chem. Commun., 1980, 45, 3008.

P. KoCovsky and V. cerny, Collect. Czech. Chem. Commun., 1980,45, 3030.
P. KoEovsky and F. TureEek, Tetrahedron Lett., 1981, 22,2699.
H. H. Wasserman and J. L. Ives, Tetrahedron, 1981, 37, 1825.
P. Horsewood, G . W. Kirby, R. P. Sharma, and J. G. Sweeney, J. Chem. SOC.
Perkin Trans.
I , 1981, 1802.
J. W. Suggs, S. D. Cox, R. H. Crabtree, and J. M. Quirk, Tetrahedron Lett., 1981, 22, 303.
A. Kasal, Collect. Czech. Chem. Commun., 1981, 46, 1839,
B. M. Trost, Acc. Chem. Rex, 1980, 13, 385.
295
paper was reported49 for the mechanistic

of the stereochemistry of a(4-6q)-PdCl complexes from A4-3-0x0-steroidsconfirming the initial preferential
loss of the 6p-H in the enolization, which is catalysed by the Lewis acids Pd'ICl, or
PdC1,2-, followed by intramolecular a-face transfer of the Pd from oxygen to
carbon. Oxidation with pyridine chlorochrornate in Fyridine and acetylation with
acetic anhydride in pyridine of the 17-hydroxy-group of the a-(4--6q)-PdCl
complex (36) proceeded normally although the products were largely obtained as
x-ally1 pyridine cornplexe~.~~

Oxidation of x-ally1 palladium complexes with Crv'
in DMF-ether containing a trace of sulphuric acid was reported to give the corresponding a,p-unsaturated ketones and is exemplified by the conversion of the
complex (37) into 5a-cholest-2-en-1-one and Sa-cholest-l-en-3-0ne.~~
Reaction of Fe(CO), with the epoxy-vinylcholestane (38) gave the complexes
(39) and (40) which were oxidized with Ce'" ammonium nitrate, the former giving
a mixture of the lactones (41) and (42) and the latter giving only the 8-lactone (42).53
(39)
Aromatic Compounds.-Regioselective mercuration at position 2 was reported for

oestradiyl 3-methyl ether 17-acetate with Hg(OAc)2-CH,CN and allowed the
preparation of the 2-chloro-, -bromo-, and -iodo-deri~atives.~~
The major product
(41 %) of the reaction between oestrone and Ph5Bi was reported to be the 2,448
50
61
52
5s
54
D. J. Collins, W. R. Jackson, and R. N. Timms, Aust. J . Chem., 1980,33,2663.

See Reference 6, p. 193.
D. J. Collins, W. R. Jackson, and R. N. Timms, Aust. J. Chem., 1980, 33,2761.
J. Y . Satoh and C. A. Horiuchi, Bull. Chem. Sac. Jpn., 1981, 54, 625.
G. D. Annis, S. V. Ley, C. R. Self, and R. Sivaramakrishnan,J. Chern. SOC.,
Perkin Trans. I ,
1981,270.
E. Santaniello and P. Ferraboschi, J. Chem. SOC.,Chem., Cornrnun. 1981, 217.
296
diphenyl derivative and the minor product (18 %) was the 4-phenyl derivative.55
Oestradiol reacted in a similar manner but oxidation of the 17-hydroxy-group also
occurred.
4 Carbonyl Compounds
Reduction.-Further
were reported on the use of poly(N-isopropyliminoalane) as a selective reducing agent for steroidal dicarbonyl compounds and
selective reduction of the 6-0x0-group was reported for 3a,5-cyclo-5a-androstane6,17-dione and 3cr,5-cyc10-5a-pregnane-6,20-dione.~~
A reinvestigation of the
Clemmensen reduction of tigogenin established that the major products were
tetrahydrotigogenin (43) and furostan (44) both of which were relatively
Reductive cyclizations of the acetylenic-5-ox0-5,6-secocholestanes(45) and the
(43)
R
= H or Me, n
R=H.n=2
(45) R
olefinic analogue (46) (inter a h ) using Na-NH,THF and Na-THF were compared
with those reported earlier for C,oH,Na-THF.59 The presence of ammonia in the
reducing medium allowed reduction to the secondary alcohol to compete with the
reductive cyclization and from a study60 of these competing reactions it was concluded that alkali metal-ammonia reductions of enolizable or a,&unsaturated
ketones proceeds through the vicinal dianion. Reduction of A4-3-0x0-steroidsto the
3-0x0-compounds was achieved by treatment of the pyrrolidinium salts with
1,4-dihydropyridine derivatives.61
D. H. R. Barton, J.-C. Blazejewski, B. Charpiot, D. J. Lester, W. B. Motherwell, and M. T.
Barros Papoula, J . Chem. SOC.,Chem. Commun., 1980, 827.
56 See Terpenoids and Steroids ed. J. R. Hanson (Specialist Periodical Reports), The Chemical
Society, London, 1978, Vol. 8, p. 240.
5 7 M. P. Paradisi and G . P. Zecchini, Tetrahedron, 1981, 37, 971.
5 8 M. Zachis and J. A. Rabi, Tetrahedron Lett., 1980, 21, 3135.
5 9 S. K. Pradhan, S . R. Kadam, J . N. Kolhe, T. V. Radhakrishnan, S. V. Sohani, and V. B.
Thacker, J . Org. Chem., 1981, 46, 2622.
6D S . K. Pradhan, S . R. Kadam, and J. N. Kolhe, J . Org. Chem., 1981,46, 2633.
R. A. Gase and U. K. Pandit, Red. Trav. Chim. Pay-Bas, 1980, 99, 334.
55
297
Other Reactions.-A review on the preparative methods of acetal formation contains

steroidal examples.62Periodic acid was reported to be useful for regeneration of
ketones from t h i o a c e t a l ~The
. ~ ~ reaction of lithium acetylide with the 14p-hydroxy17-ketone (47) gave stereospecifically the 17p-hydroxy-compound (48)whereas the
&
H
{I3
OH
"(48)
(49)
(47)
R'
R'
=
=
Me,Si
&
'
H
CECH, R2 = OH
OH, R2 = C E C H
(50)
w
\
( 5 5 ) 12a and 12p
(54)
OAc
(57)
(56)
epimer (49) was obtained from the reaction with the equivalent acetylenic Grignard
reagent.64Scr-Cholestanewas converted into 3,3-dimethyl-5cr-cholestane
by sequential treatment with MeMgX, ZnC1,-HCI, and ZnMe2-TiC1,.65 A new method for
1,2-transposition of ketones was appliedaa to 5cc-cholestan-3-one. The initially
formed vinyl silane (50)67was oxidized with MCPBA to the epoxide (51) which on
62
63
64
65
66
F. A. J. Meskens, Synthesis, 1981, 501.

J. Cairns and R. T. Logan, J. Chem. SOC.,Chem. Commun.,1980, 886.
J.-C. Beloeil, M. Bertranne, M. Fetizon, and T. Prangk,J . Chem. SOC.,Chem. Commun., 1981,
363,
M. T, Reetz, J. Westermann, and R. Steinbach, Angew. Chem., Znt. Ed. Engl., 1980, 19, 900.
W. E. Fristad, T. R. Bailey, and L. A. Paquette, J. Org. Chem., 1980, 45, 3028.
L. A. Paquette, W. E. Fristad. D. S. Dime, and T. R. Bailey, J . Org. Chem., 1980, 45, 3017.
298
reduction with LiAlH, gave the hydroxy-silanes (52) and (53). Final oxidation with
chromic acid gave a mixture of the 2- and 3-ketones. The Prins reaction of lumihecogenin acetate (54) was reported to give the 14-hydroxy-compounds (55).68 A
novel base-catalysed cleavage of steroids containing the 17-dihydroxyacetone group
was reported to yield 1 7 - 0 x o - ~ t e r o i dAttempted
~.~~
acetylation of the novel marine
sterol (56) was reported7* to give the retro-aldol product (57).
of hydrocyanation of 3-oxo-Al-steroids and analogues were
The full
reported, 73 and a full account was available for the acid- and base-catalysed
additions of thiols to 3-OXO-A'- and related s t e r o i d ~and
, ~ thiourea
~ ~ ~ ~ was observed
to react with androst-l-en-3-ones to give the adduct (58). Reaction of 2-bromo-Al729
(59) R
(60) R
(61) R = C02Et
= C0,Et
= CN
(62) R
CN
and - A 1 ~ 4 ~ 6 - ~ t with
e r ~ i malonic
d~
ester and tetramethylguanidine gave the cyclopropanes (59) and (61) respectively as expected. 76 However, the cyano-derivatives
Me,N
(Me,N),C=O
(60)
f-
Scheme 1
68
Be
70
71
72
73
14
76
76
P. Welzel, B. Janssen, and H. Duddeck, Annalen, 1981, 546.

S . S. Simons Jr., M. J. Merchlinsky, and D. F. Johnson, Steroids, 1981, 37, 281.
G. Cimino, S. De Rosa, S. De Stefano, G. Scognamiglio, and G . Sodano, Tetrahedron Lett.,
1981,22,3013.
C. Agami, M. Fadlallah, and J. Levisalles, Tetrahedron, 1981, 37,903.
C. Agami, M. Fadlallah, and J. Levisalles, Tetrahedron, 1981, 37, 909.
M. M. Campbell, V. B. Jigajinni, and R. H. Wightman, J. Chem. Res. (S)., 1981, 185.
M. Kocor, W. Kroszczyiiski, and J. Pietrzak, Synthesis, 1980, 742.
299
(60) and (62) were also isolated and the suggested mechanism from the initial
Michael adduct from the 2-bromo-Al-compound is outlined in Scheme 1.
Reactions Involving Enols or Enolic Derivatives.-The full account was reported
for the dehydrogenation of ketones using benzene seleninic anhydride. 77 Further
studies were reported on catalysts specific for the isomerization of A5-cholestenone
to A4-cholestenone.78
8a-Methylation of the 7-OXO-1
3,17-seco-steroid (63) was reported79with MeIAmtOK and efficient2 1-methylation of 20-oxo-pregnanes was achieved with MeILDA and led to the synthesis of 16a,17cc,21-trimethylpregnanes.
8o a-Thiocyanation
THPO&OTHP
(63)
of ketones was reported using copper(I1) thiocyanatesl and 21-hydroxylation of
pregnenolone exemplified a general procedure of a-hydroxylation of ketones
involving oxidation of the silyl enol ethers with OsO,-N-methyl morpho1ine-Noxide.82 6a-Methylation of the 3-oxo-androst-4-ene(64) was achieved by allowing
the silyl dienol ether (65) to react with dithienium fluoroborate and treatment of the
resultant substituted enone (66) with Raney nickel.83 The enol triflate (67) was
(66)
D. H. R. Barton, D. J. Lester, and S. V. Ley, J. Chem. SOC.,Perkin Trans. 1, 1980, 2209.
7 8 A. Fauve and A. Kergomard, Tetrahedron, 1981,37, 1697.
79 H.-R. Schlatter and W. Graf, Helv. Chim. Acta, 1980, 63, 1554.
80 J. Cairns, R. T. Logan, G. McGarry, R. G. Roy, D. F. M. Stephenson, and G. F. Woods,
J. Chem. SOC.,Perkin Trans. 1, 1981, 2306.
S. M. Ali, D. Clarke, G. R. Cliff, and G. A. Morrison, J. Chem. Res. ( S ) , 1981, 234.
J. P. McCormick, W. Tomasik, and M. W. Johnson, Tetrahedron Lett., 1981, 22, 607.
8a I. Paterson and L. G. Price, Tetrahedron Lett., 1981, 22, 2833.
77
300
coupled with lithium dimethyl cuprate and with lithium diphenyl cuprate to give
3-methylcholest-2-ene and 3-phenylcholest-2-ene respectively.s4 Ketones or their
derived enol acetates were converted into the cc-iodo-ketones with iodine and
copper(r1) acetate. 85
0ximes.-Treatment of ketoximes with acetyl chloride-acetic anhydride-tertiary
amine followed by hydrolysis gave the a-acetoxy-ketones and was exemplified by
the conversion of 5cc-cholestan-3-one oxime to the 2a-acetoxy-3-oxo-derivative.~6
An investigation of the mechanism of the Moffatt fragmentation of oximes suggested that the bond which breaks is antiperiplanar to the h y d r o x y - g r ~ u pAccor.~~
dingly, the Z-isomers (68) gave the 13,17-seco-nitrile (70) through the intermediate
(69) where as the E-isomers (71) gave the 16,17-seco-nitrile (73) through the
intermediate (72). Reaction of 6-oximino-steroids with trimethylsilyl chloride was
reported to give the cc-chloro-derivatives.19
(71) 16a or 16p
+O
(73)
5 Compounds of Nitrogen, Selenium, Sulphur, and Tellurium
A review on the acid promoted decomposition of a-diazoketones contains some

steroidal examples.88 The full account was reported of the conversion of cc-azidoketones into cyano-carboxylic acids promoted by bromine in acetic a ~ i d . 8A~
general review on new reagents in natural product chemistry included the deamination of amines via the isonitriles, isothiocyanates, and isoselenocyanates reported
84
85
B6
87
88
J. E. McMurray and W. J. Scott, Tetrahedron Lett., 1980, 21, 4313.

C. A. Horuichi and J. Y. Satoh, Synthesis, 1981, 312.
G. S. Reddy and M. V. Bhatt, Synthesis, 1981, 223.
J. Pfenninger and W. Graf, Helv. Chim. Acra, 1980, 63, 2338.
A. B. Smith and R. K. Dieter, Tetrahedron, 1981, 37, 2407.
T. T. Takahashi and J. Y. Satoh, J. Chem. SOC.,Perkin. Trans. I , 1980, 1916.
301
earlier. Reaction of cc, p-epoxy-O-thiocarbonylimidazolederivatives of steroidal

alcohols were reported to react with AIBN-Bu,SnH to give the allylic alkoxy
radical which was converted into the allylic alcohol or a rearranged product
dependent on the mode of addition of the B U , S ~ HFor
. ~ ~example, the cholestane
derivative (74) with AIBN when added to excess Bu,SnH (inverse addition) gave
the allylic alcohol (75) and a small amount of the A-nor-B-homo-ketone (76).
However, the latter compound became the major product if Bu,SnH was added to a
mixture of the cholestane derivative (74) with AIBN. This reaction, in the inverse
addition mode, provides an alternative to the Wharton reaction and the pregnane
epoxy-O-thiocarbonylimidazole(77) was converted into the allylic alcohol (78).
&--OH
(77)
Steroidal alcohols were reported to be deoxygenated by conversion into the
selenocarbonates and reduction with Bu,SnH-AIBN. Carboxylic acids were
similarly converted into the selenoesters which on treatment with Bu,SnH-AIBN
gave mainly the aldehyde or the nor-alkane depending whether xylene or benzene
was used as solvent. 92 Deoxygenation was reportedg3in full for N,N-dialkylaminothiocarbonyloxyalkanes by treatment with potassium in t-butylamine containing
18-crown-6.
(79)
x =0
(80) X
So
S1
92
s3
H2
(82) R' = SCN, R2= I

(83) R1= NCS, R2 = I
(84) R' = I, R2= NCS
D. H. R. Barton and W. B. Motherwell, Pure Appl. Chem., 1981,53, 1081.

D. H. R. Barton, R. S. Hay Motherwell, and W. B. Motherwell, J . Chem. Soc., Perkin Trans.
I , 1981, 2363.
J. Pfenninger, C. Heuberger, and W. Graf, Helv. Chim.Acta, 1980, 63, 2328.
A. G. M. Barrett, P. A. Prokopiou, and D. H. R. Barton, J. Chem. SOC.,Perkin Trans. I , 1981,
1510.
302
Treatment of 3~-t-butyltellurocarbonyloxy-5a-cholestane
with benzene seleninic
anhydride gave the cholestanyl ester (79) whereas with sodium hydrogen telluride
the ethers (80) and (81) were ~ b t a i n e d . ~
Reaction
*
of the vic-iodothiocyanate (82)
and the iodoisothiocyanates (83) and (84) with BuLi at room temperature gave
a n d r o ~ t - 2 - e n eit; ~was
~ observed that the diaxial nature of the substituents was
responsible for the elimination. It was reported that the reaction of the aminomesylate (85) with basic reagents gave Wagner-Meenvein rearrangement products
OMS
(85) R = H
(86) R
MS
(87) R
(88) R
H
MS
(89) 16P917P
(90) 16a,17a
SCH2CH,N3
H
(94)
. ,
(95)
whereas the isomer (87) was converted into the 16a-amino-17P-hydroxy-compound

and the 16a,I7a-aziridine. 96 The N-mesylaziridines (89) and (90) were smoothly
obtained by reaction of the 16,17-trans-mesylamidomesyloxy-compounds
(86) and
(88) respectively with Bu'OK-DMSO. Further studies on the dehydrogenation of
lactams were reported with benzene seleninic anhydride. 9 7 Heating the azidocholestenone (91) in xylene was reportedg8to give the cyclic enamide (92). Hydrozirconation of the thioketone (93) followed by reaction with a variety of electrophiles led to a variety of sulphur compounds and exemplified quite a general
reaction sequence.99Thus, for example, sequential treatment of (93) with Cp,ZrHCl
and MeCOCH=CH, gave the 0x0-thioether (94). A comparative study was
g4
85
A. G. M. Barrett, R. W. Read, and D. H. R. Barton, J . Chem. SOC.,Perkin Trans. I , 1980,2191.

R. C. Cambie, D. Chambers, P. S. Rutledge, and P. D. Woodgate, J . Chern. Soc., Perkin
Trans.I, 1981, 40.

86
g7
gg
B. Schoenecker and K. Ponsold, J. Prakt. Chem., 1981, 323, 223.

T. G. Back, J . Org. Chem., 1981, 46, 1442.
A. G. Schultz and R. Ravichandran, J. Org. Chem., 1980, 45, 5008.
D. E. Laycock and H. Alper, J . Org. Chem., 1981,46,289.
303
reported of the action of H202and p-nitroperbenzoic acid on the pyrroline (95)

and the derived oxaziridine and nitrone .loo
6 Molecular Rearrangements
The previously observed backbone rearrangement of cholest-5-ene to cholest13(17)-ene in acetic acid-toluene-p-sulphonicacid and the subsequent slow epimerization at C-20 were shown by a deuterium incorporation study to involve a
series of carbo-cation-olefin equilibria.lo1The full account was reported for the
BC1,-catalysed backbone rearrangement of 4,4-dimethyl-6,20-epoxy-5a-androstane.lo2The oxetane (96) was reportedlo, to react with RCN-HBF, to give the
~@HI3F4
{j$F
(99)
AcO
(96) 16P917P
(97) 16a,17a
(98)
hydro-oxazine salts (98) while its 16,17-epimer (97) underwent rearrangement to

the A13-l7-methyl compound (99). The 17a-propynyl-17P-hydroxy-11B-hydroxyandrostadienone (100) was observed to give a high yield of the A13-17-methyl
derivative (101) when treated with BF,-Et,O in acetic acid or a~etonitri1e.l~~
However, in benzene, chloroform, or carbon tetrachloride participation of the propynyl
group was favoured and the major product was the 13a-propynyl-118,I7B-epoxide
H. Dadoun, J.-P. Alazard, and X . Lusinchi, Tetrahedron, 1981, 37, 1525.
D. E. Akporiaye, R. D. Farrant, and D. N. Kirk, J. Chem. Res. ( S ) , 1980, 210.
lo8 M. Fetizon and G. Sozzi, Tetrahedron, 1981, 37, 61.
lo3 G. Schneider, L.Hackler, and P. Sohhr, Tetrahedron Lett., 1981,22, 341.
lo4 G. Teutsch, C. Lang, R. Smolik, J. P. Mornon, and J. Delettrk, Tetrahedron Lett., 1981, 22,
loo
lol
327.
304
(102). Further rearrangement of the 11P, 17p-epoxide (102) with SnC1, in acetic anhydride gave cyclobutene (103). A convenient method for the introduction of the
isopropenyl group into a$-unsaturated ketones involved the BF,*Et,O-catalysed
cleavage of the allene-enone photo-adducts.lo5 Thus, for example photo-adduct
(104) gave the 4-isopropenyl-A4-3-oxo-compound
(105). The BF,-Et,O-catalysed
(104)
(105)
rearrangement of the 3,19-epoxy-androstane (106) to the 10-formyl-compound
(108) was shown106 to involve a reversible 1,5-hydride ion shift which was highly
stereoselective for the H, and involved the intermediate (107). Whereas-the
19-hydroxy-5p76p-epoxides
(109) underwent cleavage of the 10,19-bond with BF,
(109) R
(110) R
AC
BF3
(1 12)
gas in benzene to give the dienes (1 1 I), the equivalent 19-acetoxy-compounds (1 10)
(1 12):lo7A study of the acid-catalysed
rearranged to the 5-formy~-~-n0r-~0mpounds
reactions of 3p-acetoxy-5-hydroxy-5ct-cholestan-6-one
and the 3p-tosylate was
lo5
lo6
'07
D. K. M. Duc, M. Fetizon, I. Hanna, and S. Lazare, Synthesis, 1981, 139.

G. Acklin and W. Graf, Helv. Chim. Acta, 1980, 63, 2343.
H. Mastalerz and P. Morand, J. Chem. SOC.Perkin Trans. 1, 1981, 154.
305
(1 17)
(1 18)
reported.lo8Aromatic ~-ring-6-oxo-compounds
were the major products from the
former with CC1,CO2H, ClCH2C02H,or CBr,C02H whereas the latter gave mainly
the dienone (113) and the diketone (114) with KHS04 and HBr respectively.
Reaction of the 1cc,2cc-rnethyleneandrost-4-en-3-one
(1 15) and the 2a73a-methyleneandrost-6-en-4-one (1 17) with HBr gave the simple bromomethyl derivatives (1 16)
and (1 18) respectively and no dienone-phenol rearrangement was reported.lo9
*p;
BzO-
(124) lop
(125) 10a
lo*
(126) R = Bz, R2 = AC
(127) R = Ac, R2= BZ
RIO
(128) R1= Bz, R2= Ac; 3a,lOa

(129) R = Ac, R2= Bz; 3f3,lOp
J, J. Jagodzifiski, J. Gumulka, and W. J. Szczepek, Tetrahedron,1981, 37, 1015.

J. R. Hanson and S. G . Knights, J. Chem. SOC.,Perkin Trans. I , 1981, 25.
loB
0r2
306
The full account was reported for the study of the intramolecular ene reactions
of the enols of 5-vinyl-3-oxo-steroidsand an examination of the photolysis of the
bridged bicyclic ketone (1 19) was incorporated.110A by-product of the reaction of
3p-tosyloxy-5,6p-dihydroxy-5~-cholestane
(120) with ButOK-Bu'OH was reportedlll
to be the A-nor-compound (123) which arose from an ene reaction of the enol(l22)
of the fragmentation product (121). Buffered acetolysis of the tosylate (124) gave
the A-homo-compounds (125) and (126) while the tosylate (127) gave the related
A-homo-compounds (128) and (129).lI2 Thermally and photochemically induced
fragmentations of the hypoiodites of 3-methylcholest-5-en-3-01,1~~
4,4-dimethylcholest-5-en-3p-01,~~~
cholesterol, epicholesterol, and 3a,4,4-trimethyl-cholest-5-en3p-o1115which were generated in situ from the parent alcohols were reported to give
a variety of products all derived from the oxyl radicals (130).
(130)
Oxidation of cholestane-2,3-dione with thallium(m) acetate gave the A-nor-pketo-ester (131) whereas a low yield of the keto-lactones (132) was obtained from
3,4-diketo-steroids.l16
(131)
(1 32)
An investigation into the migratory aptitudes of C-2 versus C-4 in Beckmann,

Schmidt, and Baeyer-Villiger reactions employed 13C n.m.r. spectroscopy and
demonstrated that all reactions proceeded with migration of both C-2 and C-4
0
OOH
(135) R = 0
(136) R = p-Cl, H
P.Yates and F. M. Winnik, Can. J. Chem., 1981, 59, 1641.
D.S.Brown, R . W. G. Foster, B. A. Marples, and K. G. Mason, Tetrahedron Lett., 1980, 21,
(133)
l10
ll1
5057.
115
J. M. Gerder, A. W. Norman, and W. H. Okamura, J. Org. Chem., 1981, 46, 599.

H Suginome and N Maeda, Bull. Chem. SOC.Jpn., 1980, 53,2621.
H.Suginome and N. Maeda, Bull. Chem. SOC.Jpn., 1980, 53, 2626.
H. Suginome, A. Furusaki, K. Kato, H. Maeda, and F. Yonebayashi, J. Chem. SOC.,Perkin
116
A. M.Maione, A. Romeo, S. Cerrini, W. Fedeli, and F. Mazza, Tetrahedron, 1981,37, 1407.
112
113
114
Trans. 1 , 1981, 236.
307
notwithstanding earlier reports to the ~0ntrary.l~'

Acetylation of the 5-hydroperoxide (133) gave the ~-homo-6-oxa-compound (134) demonstrating the preferred
alkenyl versus alkyl migration for this Criegee rearrangement.ll* Baeyer-Villiger
oxidation of the 5P-methylcholest-9-enedione
(135) gave a variety of products and
interestingly the related chloro-ketone (136) gave the 5a-methyl-lactone (137).l19
Reaction of the A14-17-0x0-androstsne (138) with alkaline hydrogen peroxide led
to three novel ring D-cleaved products (139), (140), and (141) which were isolated
0
(138)
from the acidic fraction of the product after methyl ester formation and acetylation.lS0 Oxidation of cholest-4-ene-3,6-dione with excess perbenzoic acid in the
presence of toluene-p-sulphonic acid gave the oxetalactones (142) and (143).121
The a-azido-sulphide (145), which was generated in situ from the thioacetal (144),
was reported122to undergo SnC1,-catalysed rearrangement to the cyclic iminothiomethyl ethers (146) and (1 47).
MeS
&
MeS
Mes@NS
(145)
(144)
(144)
11'
11*
lln
121
122
(147)
V. Dave, J. B. Stothers, and E. W. Warnhoff, Can. J. Chem., 1980, 58, 2666.

J. A. M.Peters, N. P. van Vliet, and F. J. Zeelen, Red. Truv. Chim. Pays-Bas, 1981, 100,226.
Shafiullah, M. A. Ghaffari, and H. Ali, Tetrahedron, 1980, 36, 2263.
M. Bialer, Tetrahedron Lett., 1981, 22, 2683.
M.S.Ahmad, I. A. Khan, and N. K. Pillai, Tetrahedron, 1980, 36, 2341.
B. M. Trost, M. Vaultier, and M. L. Santiago, J . Am. Chem. SOC.,1980, 102, 7929.
308
7 Functionalization of Non-activated Positions
Reaction of 6p-hydroxy-steroids with ceric ammonium nitrate was reported to give

the 6p, 19-epoxide~,1~~
and fragmentation of 5- and 19-hydroxy-compounds were
also reported. A detailed investigation of the hypoiodite reaction and the related
Pb(OAc), oxidation of a 5a-bromo-6p-hydroxy-compoundindicated that for the
former a halocarbon solvent promotes 6p, 19-epoxide formation.lz4Photolysis of
the 17a-iodobenzoate (148) with PhICI, gave the 9a-chloro-derivative (149) which
on thermolysis gave a good yield of the 9(11),16-diene (150).125 Photolysis of
(150)
nitroamines wth I,-Pb(OAc)4 or I,-HgO was reported to generate the nitroamine

radicals which led to functionalization of non-activated positions.12s Thus the
6p-nitro-aminocholestanes (I 5 1) gave the N-nitropyrrolidines (152) and the
(151) R
H or OAc
(152)
H or OAc
(153)
lZ3
lz4
lZ5
126
V. Balasubramanian and C. H. Robinson, Tetrahedron Lett., 1981, 22, 501.

B. H. Jennings and L. M. Yelle, Sreroidr, 1981, 37, 7 .
U. Kerb, M. Stahnke, P.-E. Schulze, and R. Wiechert, Angew. Chem., Int. Ed. Engl., 1981,20,
88.
R. Hernhndez, A. Rivera, J. A. Salazar, and E. Suhrez, J. Chem. Soc., Chem. Commun., 1980,
958.
309
nitroamine (153) after the photolysis and reaction with AgOAc gave the similar
18-functionalized derivative (154). Jervine was reportedla' to be transformed into
the 18-functionalized c/D-trans-D-homo-c-nor-compound
(153, the 1l-oxofunction of which was readily removed by Wolff-Kishner reduction.
8 Photochemical Reactions
Aspects of photosensitization in organic synthesis were reviewed12* and stereospecific and regiospecific photoreactions inside the channels of choleic acids were
r e ~ 0 r t e d . lIrradiation
~~
of saturated acids or esters was reportedlsO to lead to
Norrish type I1 reaction or a 1,Zelimination and was exemplified by conversion of
cholanic acid or its ethyl ester into the A20(22)-compound
(156). Photolysis of the
PAC
(157)
enol ester (157) gave131the P-diketone (158) through a photo-Fries type rearrangein methanol saturated with
ment. Irradiation of 3a,5-cyclo-5a-cholestan-7-one
oxygen was reported132to give the 7-oxa-compound (159) along with the 7,S-seco-
(159)
(160)
H. Suginome, H. Ono, and T . Masamune, Bull. Chem. SOC.Jpn., 1981, 54, 852.
l Z 8A. Albini, Synthesis, 1981, 249.
12@ R. Popovitz-Biro, H. C. Chang, C. P. Tang, N. R. Shochet, M. Lahav, and L. Leiserowitz,
Pure. Appl. Chem., 1980,52,2693.
l3O G.Wolff and G. Ourisson, Tetrahedron Lett., 1981, 22, 1441.
131 D.Veierov, Y.Mazur, and E. Fischer, J. Chem. SOC.,Perkin Trans. 2, 1980, 1659.
lS2 H. Suginome and C.-M. Shea, Bull. Chem. SOC.
Jpn., 1980, 53, 3387.
lZ7
3 10
ester (160). The a,@-unsaturated8-lactone (161) was converted into the aldehydeSimilar photolyses in methanol of the
ester (162) by irradiation in rnethan01.l~~
(161)
(162)
analogous %lactones (163) gave the 5,l O-seco-derivatives (164) whereas the isomeric
&lactones (165) led to the 1,lo-seco-derivatives (166).13* A further study was
reported135 of the photochemical reactivity of 3-oxo-h5(lo)-steroids. Photolysis of
(163)
, a aR
M = H or Me
(164) R
=H
&
or Me
R-N
0
(166) R
9 &
=H
0'
or Me
(167)
C8H1,
AcO
(168)
(1 69)
the related A-homo-enone (167) in benzene was shown to give the spiro-ketone
(168), probably via a singlet or short-lived triplet excited
A triplet-sensitized
photo-equilibrium may be established between vitamin D, and trans-vitamin D,
in which the equilibrium position depends on the energy of the triplet sensitizer.
In the presence of oxygen selective photo-oxygenation of the trans-isomer was
re~0rted.l~'
As would be predicted from steric considerations, the photo-adduct
(169) derived from allene and 3 ~-acetoxycholest-8-en-7-one
has the 8a,9a-configuration. However, since the isomeric As-1 l-oxo-compound did not react, it is
133
l3*
A. Canovas and J.-J. Bonet, Helv. Chim. Acta, 1980, 63, 2390.
A. CCmovas, J. Fonrodona, J.-J. Bonet, M. C. Brianso, and J. L. Brians6, Helv. Chim. Actu,
1980, 63,2381.
J. R. Williams and A. Abdel-Magid, Tetrahedron,1981,37,1675.

136 J. R. Williams and G. M. Sarkisian, .
I
Org.
. Chem., 1980, 45, 5088.
n7 J. W. J. Gielen, R. B. Koolstra, H. J. C. Jacobs, and E. Havinga, Recl. Trav. Chim. Pays-Bas.,
99,306.
la6
31 1
Steroid Reactions und Partial Syntheses
confirmed that not only steric considerations operate and that the configuration of
the adducts may be predicted assuming an intermediate species which is trigonal in
the a-position and pyramidal in the p-position.13* Photo-Beckmann rearrangement
of 4,4-dimethylcholest-5-en-3-oneoxime and 4,4,6-trimethylcholest-5-en-3-one
oxime gave essentially the predicted lactams and little or no nitrile in contrast to the
SOC1,-induced Beckmann rea~rangernent.~~~
It is inferred that ionic or radical
species derived by cleavage of the 3,4-bond are not involved in the photo-Beckmann
rearrangements. The photo-Beckmann rearrangement of ~-nor-Sa-androstan-l6one oxime gave140,inter alia, a 13a-lactam. A similar inversion had previously been
reported for a 17-ketoximeand in both cases some form of open-chain intermediate
is implied. The photo-Beckmann rearrangement of 3a,5-cyclo-5a-cholestan-7-one
oxime was u n e ~ c e p t i o n a l .The
~ ~ ~photolysis of ~-nor-Sa-androstan16-one acetyl
hydrazone in the presence of oxygen gave the expected142lactams and some
inversion at C-13
SECTION B: Partial Syntheses
9 Cbolestane Derivatives and Analogues
Recent studies in marine sterols were reviewed144and related to this is a review of
sterol biosynthesis and metabolism in marine invertebrate^.^^^ Mutasterol (171), a
ii, iii
(171)
Reagents: i, LDA-MeCOCMe,Et; ii, H,-Pd/C; iii, BuLi-Ph,P+MeBr-; iv, H30+
Scheme 2
J. F. Blount, G. D. Gray, K. S. Atwal, T. Y. R. Tsai, and K. Wiesner, Tetrahedron Lett., 1980,
21,4413.
139 H. Suginome, N. Maeda, Y.Takahashi, and N. Miyata, Bull. Chem. SOC.
Jpn., 1981,54,846.
loo
H. Suginome and T. Uchida, Bull. Chem. SOC.Jpn., 1980, 53, 2292.
1 4 1 H. Suginome and C.-M. Shea, J. Chem. SOC.
Perkin Trans. 1, 1980, 2268.
14e See Reference 6, p. 209.
143 H. Suginome, T. Uchida, K. Kizuka, and T. Masamune, Bull. Chem. SOC.
Jpn., 1980,53,2285.
144 C. Djerassi, Pure Appl. Chem., 1981,53,873.
14s L. J. Goad, Pure Appl, Chem., 1981, 53, 837.
138
3 12
novel sponge sterol alkylated at C-25, was synthesized from the stigmasterolderived 3,5-cyclo-aldehyde (170) as indicated in Scheme 2.14sA synthesis was
reported for 22-methylenecholestero1147
which along with (22S), (23S)methylene~ h o I e ~ t e r o 1 , 1observed
~ ~ ~ a ~to be a novel marine sterol. The key step in the synthesis
of stellasterol (173) involved the reaction of the allylic alcohol (172) with triethyl-
(172)
(173)
o r t h o a ~ e t a t e The
l ~ ~ ene reaction product (174) of ergosteryl acetate and diethyl
azodicarboxylate was reduced with Li-EtNH, to afford lichasterol (175).150
ca17
AcO&02Et
HN, C0,Et
J&
(175)
( 1 74)
Xestospongesterol(l76) and isoxestospongesterol(l77), examples of marine sterols

with q2side chains, were synthesized according to Scheme 3.151 The oxidation
of 5p-cholestane-3a,7a,12a,26-tetrol with Ag,CO,-celite gave 3cr,7cc, 12a-trihydroxy-5p-cholestan-26-a1, 7a, 12~,26-trihydroxy-5
p-cholestan-3-one, and 7a, 12%-dihydroxy-3-oxo-5p-chole~tan-26-al.~~~
A new route to chenodeoxycholic acid163
and a novel synthesis of 25-a~acoprostanel~~
from lithocholic acid were reported.
Partial synthesisof halosterols epimeric at C-20 established that the natural material
(178) had the 20R-~0nfiguration.l~~
A number of stereocontrolled syntheses of the
steroidal side chain were r e p ~ r t e d . l ~ ~Reaction
- l ~ ~ of Z- 17(20)-pregnenes (179)
L. N. Li, U . Sjostrand, and C . Djerassi, J. Am. Chem. SOC.,1981, 103, 115.
J. Zielinski, H. Li, T. S. Milkova, S. Popov, N. L. Marekov, and C. Djerassi, TetrahedronLett.,
1981, 22,2345.
148 P. A. Blanc and C . Djerassi, J. Am. Chem. Soc., 1980, 102, 7113.
148 M. Anastasia and A. Fiecchi, J. Org. Chem., 1981, 46, 1726.
150 M. Anastasia and A. Fiecchi, J . Chem. SOC.,
Perkin Trans. 1, 1981, 2125.
151 L. N. Li and C. Djerassi, J . Am. Chem. SOC.,1981, 103, 3606.
152 B. Dayal, G. S. Tint, A. K. Bhatta, S. Shefer, and G. Salen, Steroids, 1981, 37, 205.
lS3 T. Ida and F. C. Chang, J . Org. Chem., 1981,46,2786.
154 T. W. Gibson, Synthesis, 1980, 995.
156 J. M. Joseph and W. R. Nes, J. Chem. SOC.,Chem. Commun., 1981, 367.
156 W. G. Dauben and T. Brookhart, J. Am. Chem. SOC.,1981,103,237.
15 A. D. Bateho, D. E. Berger, M. R. Uskokovid, and B. B. Snider, J. Am. Chem. SOC.,
1981,103,
1293.
158 M. M. Midland and Y. C. Kwon, J . Org. Chem., 1981,46,229.
158 J. S. Temple and J. Schwartz, J. Am. Chem. SOC.,1980, 102, 7381.
J. P. Marino and H. Abe, J. Am. Chem. Sac., 1981, 103,2907.
146
14
313
I
OMe
--\
b i , iii
v,
v1
(176) 252
(177) 25E
Reagents: i, LDA-Me,CHCO,Me; ii, EtMgBr; iii, SOC1,-pyridine; iv, H,O+; v, MCPBA;
vi, Me,Si-SiMe3-KOMe-HMPA
Scheme 3
(178)
with diethylaluminium chloride and methyl p r ~ p i o l a t e or
l ~ with
~
ethylaluminium
dichloride and methyl p r ~ p i o l a t gave
e ~ ~ the
~ A15p22-dieneesters (180) which had the
natural configuration at C-20 and which could be hydrogenated to give the 17pconfiguration. Hydroboration of 2-1 7(20)-pregnenes (179)with9-borabicyclo[3.3.1Jnonane and subsequent reaction with chloroacetonitrile and base led to the
21-cyano-compounds (181).158 Reaction of the x-ally1 palladium complex (182)
with isohexenyl zirconium gave the diene (1 83) with the natural configuration at
C-20.159 The 15p,16p-epoxy-Z- 17(20)-pregnene (184) was allowed to react with
lithium isohexylcyanocuprate to give the 15~-hydroxy-A16-compound
(185) which
could be modified to give cholesterol.lG0
314
Syntheses were reportedlsl for the 20-epimers of 21-nor-5a-cholane-20,24-diol

(1 87) from the methyl ester (186). Cholest-4-en-3-one was convertedls2 into
24-hydroxychol-4-en-3-one
in one step by treatment with CF,C0,H-H2S04 at
(186)
0 "C. A key step in the stereoselective synthesis of 24,25- and 25,26-dihydroxycholesterol is the asymmetric reduction of the A25-24-oxo-compound(188) using a
complex of LiAlH, and optically active 2,2'-dihydroxy-1,l'-binaphthyl. Thus, the
reduction of (188) with the R-( +)-dihydroxybinaphthyl gave largely the alcohol
(1 89) which was converted into the diols (190) and (19 1) as indicated in Scheme 4.1s3
A Claisen rearrangement, effected by treatment of the deuteriated substrate (192)
with ethyl orthopropionate led to the 24-deuterio-ester (1 93) which was converted
A novel synthetic approach to the
into [24R-2H]-25-hydroxyprovitamin
ecdysone side chain was demonstratedls5 with pregnenolone acetate, which was
reported to react with 2-lithio-5-methylfuran to give, after reacetylation, the AZ0-
162
laa
164
165
V. Pouzar and M. Havel, Collect. Czech. Chem. Commun., 1980, 45, 2443.
R. P. Manley, K. W. Curry, N. C. Dens, and M. D. Meyer, J. Org. Chem., 1980,45,4385.
M . Ishiguro, N. Koizurni, M. Yasuda, and N. Ikekawa, J. Chem. Soc., Chem. Commun., 1981,
115.
J. D. Meadows and D. H. Williams, Tetrahedron Lett., 1980, 21, 4373.
T. Kametani, M. Tsubuki, and H. Nemoto, Tetrahedron Lett., 1981, 22, 2373.
315
ji
iiii
?H
(191)
(190)
Reagents : i, VO(acac),-Bu'OOH ; ii, K,CO,-PrOH ; iii, LiAIHo
Scheme 4
(192)
furanoid (194). This compound, on hydrogenation, gave the 20s-furanoid (195).

Acid-catalysedcleavage of the furan ring followed by reacetylation gave the diketone
(196) which was converted into the 22,25-diols with the cholestane side chain.
A novel route was reported166for the conversion of diosgenin into a-ecdysone and
material labelled with tritium at positions 15 and 16 was prepared. Two independent
188
Y.-W.Lee, E. Lee, and K. Nakanishi, Tetrahedron Lett., 1980, 21, 4323.
316
( I 94)
syntheses of brassinolide (198) were r e p ~ r t e d ~and

~ ~the
J ~essential
~
steps for the
construction of the side chain from the aldehydes (170)16' and (197)168are shown in
Reagents : i, [BuMe,AlCH=CMePr']Li; ii, MCPBA; iii, LiBH,-BH,
Scheme 5
iii, iv
v, vi
Reagents: i, Me,CH-C = CLi ; ii, Lindlar catalyst-H2; iii, Bu'OOH-VO(acac),; iv, Ac,Opyridine; v, HCN-Et3A1; vi, KOH
Scheme 6
16'
168
S. Fung and J. B. Siddall, J. Am. Chem. Soc., 1980, 102, 6580.

M. Ishiguro, S. Takaksuto, M. Morisaki, and N. Ikekawa, J . Chem. SOC.,Chem. Commun.,
1980,962.
317
Schemes 5 and 6 respectively.Reformatsky reaction of 3@,21-diacetoxy-pregn-5-en20-one (199) was reported169to give the 20-acetoxy- and 20-hydroxy-lactones(200)
which were converted into 3@,23-diacetoxy-24-norchol-5-ene
via hydrogenation of
the A20-compound(201) allowing incorporation of isotopic label at C-20 and C-21.
OAc
&
AcO
(200) R
=H
or Ac
@-' &
iii, iv
0
R
(203)
Reagents: i, R-C
=CMgBr; ii, POC1,-pyridine;
iii, MPA; iv, HC0,H-H20
Scheme 7
169
A. M. Seldes, C. R. Anding, and E. G. Gros, Steroids, 1980, 36, 575.
318
Ruscogenin was converted into 1p-hydroxy- and 1a-hydroxy-cholesterol derivat i v e ~3~,6~-Dihydroxy-5a-cholest-7-ene

,~~~
and the 6a-epimer were prepared from
comparison with the aglycone (202) of sepositoside A.171Preparation of 7-dehydrocholesteryl acetate free of the A4v6-dienewas accomplished by heating the A5-7@phenylsulphoxide which was obtained by oxidation of the sulphide which was in
turn prepared, in admixture with a small amount of the 7a-epimer, by sequential
treatment of cholesteryl acetate with dibromantin-NaHCO,, LiBr, and Et,NPhSH.1723-Acyl-2-oxo-5cc-cholestanes(203) were reported173to be prepared from
5a-cholestan-3-one by the sequence shown in Scheme 7 and 3-alkyl-2-oxo-Sacholestanes were obtained by direct alkylation of the 2-oxo-compound.174Syntheses
were reported175for [6a-2H]- and [6p-2H]cholest-4-en-3-onesusing slight modifications of existing procedures. Full characterization of 5-chloro-5p-cholestane
was r e ~ 0 r t e d . The
l ~ ~ synthesis of 9a-fluoro-3P-hydroxy-Sa-cholest-8( 14)-en-15-one
involved the reaction with HF of the equivalent 9a-hydroxy-compound (205) which
was synthesized by reaction of the ethyl dienol ether (204) with MCPBA-NaHC0,THF-H,O followed by hydr01ysis.l~~
All four possible 7-hydroxy-5,6-methylenecholestanes were synthesized from cholest-5-en-7-0ne.l~~The cc-methylene-ybutyrolactone (206) was
to be the major epimer of the mixture obtained
from the Reformatsky reaction of 5a-cholestan-3-one and ethyl bromomethacryldte.
10 Vitamin D, Its Metabolites, and Related Compounds

Totally synthetic approaches to vitamin D and its relatives are presented in the
Simonsen 1ecture.lB0Two syntheses of 25,26-dihydroxycholecalciferolhave been
reported and establish the 25s-configuration for the natural metabolite,181~182
and
the 25R-configurationlB2for the previously synthesized 25,26-dihydroxycholesterol,
l70
171
172
173
174
176
176
177
178
178
180
181
M. Noam, I. Tamir, E. Breuer, and R. Mechoulam, Tetrahedron, 1981, 37, 597.

F. De Simone, A. Dini, E. Finamore, L. Minale, C. Pizza, R. Riccio, and F. Zollo, J. Chem.
P. N. Confalone, I. D. Kulesha, and M. R. UskokoviC, J. Org. Chem., 1981, 46, 1030.
H. Berbalk, K. Eichinger, and R. Schuster, Synthesis, 1981, 613.
C. A. Horiuchi and J. Y. Satoh, Can. J. Chem., 1981, 59,2382.
D. J. Collins, W. R. Jackson, and R. N. Timms, Aust. J. Chem., 1980, 33, 2767.
C. W. Snoppee, R. J. Hart, and M. E. H. Howden, J. Chem. SOC.,Perkin Trans. I , 1980,
1904.
E. J. Parish and G. J. Schroepfer Jr., J. Org. Chem., 1980, 45, 4035.
L. Kohout, Collect. Czech. Chem. Commun., 1981, 46, 1828.
G. Schlewer, J.-L. Stampf, and C. Benezva, J. Med. Chem., 1980, 23, 1031.
B. Lythgoe, Chem. Suc. Rev., 1980, 9, 449.
R. Barner, J. Hubscher, J. J. Daly, and P. Schonholzer, Helv. Chim. Acta, 1981, 64, 915.
J. J. Partridge, S.-J. Shiuey, N. K. Chadha, E. G. Baggiolini, J. F. Blount, and M. R. UskokoviC,
J. Am. Chem. SOC.,1981,103,1253.
319
which was believed to have the 25s-configuration. A key step in the synthesis of
(24R)-24,25-dihydroxycholecalciferolwas the reaction of the epoxide (208) with the
(210)
sulphone (209), which led to the diol sulphone (210). The epoxide(208) was obtained
from the tosylate (207) which was synthesizedfrom D-glyCeriC acid.ls3A synthesis of
calcitroic acid (21 1) involved184the previously reported direct hydroxylation procedure of vitamin D and related compounds which was also reported in full.lS5JS6
HO'
(213) R = SiMe,But
(214) R = MeOCH,
Three syntheses were r e p ~ r t e d l ~
for~ -25-hydroxycholecalciferol-26,23-lactone
~~~
(216) which was assigned1E8~1Eg
the 23R,25S-configuration. The most stereoselective of these syntheseslsginvolves the LDA-catalysed reaction of the sulphone
(212) with the aldehyde (213) to give the hydroxy-sulphone (215) which was
modified as in Scheme 8 to give the required side chain. The sulphone (212) was
derived from S-citramalic acid. Reaction of the trideuterio-Grignard reagent (217),
which was derived from S-lactic acid, with the aldehyde (214) led to 25R-[26-2H,]las
18*
H. Takayama, M. Ohmori, and S. Yamada, Tetrahedron Lett., 1980, 21, 5027.

R. P. Esvelt, M. A. Fivizzani, H. E. Paaren, H. K. Schnoes, and H. F. DeLuca, J . Org. Chem.,
1981,46,456.
H. E. Paaren, H. F. DeLuca, and H. K. Schnoes, J . Org. Chem., 1980,45,3253.

la7 J. K. Wichmann, H. E. Paaren, M. A. Fivizzmi, H. K. Schnoes, and H. F. DeLuca, Tetruhedron Lett., 1980, 21,4667.
la8D. S . Morris, D . H. Williams, and A. F. Norris, J . Chem. SOC.,
Chem. Commun.,1981, 424.
lagS. Yamada, K. Nakayama, and H. Takayama, Tetrahedron Lett., 1981, 22, 2591.
IE5
320
b,
(215)
iii, iv
Reagents: i, Na-Hg ;ii, TsOH-H,O; iii, Ac,O-pyridine; iv, EtOH-PPTS; v, DMSO-pyridineSO3-Et3N; vi, 1,KOH; vii, 1,MeCN; viii, Bu,SnH
Scheme 8
cholecalciferol.190Methylation of the SO2 adducts of cholecalciferol with NaH

occurred regioselectively at C-6 whereas with lithium tetramethylpiperidide the
reaction was directed to C-19.1g1Extrusion of SO, (NaHC0,-EtOH-90 "C)from
the 6-methyl-derivatives was reported to give mainly the 6-methyl-previtamin

whereas the reaction with the 19-methyl-derivatives gave mainly the 19-methyl-5,6trans-vitamin. Irradiation and heating of 19-acetoxy-7-dehydrocholesterylacetate
and the 19-methoxy-analogue led to the E-vitamin D, analogues (218) and (219)
respectively,la2 whereas 19-hydroxy-7-dehydrocholesterylfragmented to give
19-n0r-A~(lO)?~-diene
(221) via a 1,7-hydrogen shift as indicated in (220). The full
account was reportedlg3 for the vinyl allene approach to 3-deoxy-1-hydroxyM.R.Lindley and D. H. Williams, Tetrahedron Lett., 1980, 21,4377.
S. Yamada, T.Suzuki, and H. Takayama, Tetrahedron Lett., 1981, 22, 3085.
l s a R. M. Moriarty and H. E. Paaren, J. Org. Chem., 1981, 46, 970.
l B 3 P. Condran Jr., M. L. Hammond, A. Mourifio, and W. H. Okamura, J. Am. Chem. SOC.,
1980,102,6259.
lgo
lgl
321
cholecalciferol and the study was extendedlg4to include the synthesis of 3-deoxy3,3-dimethyl- l-hydroxycholecalciferolsfrom the thermolysis of the vinyl allenes
(222) and (223).
Act
(218) R = AC
(219) R = Me
(222) R1= OH, R2= H
(223) R'
H, R2= OH
11 Pregnanes
Three new approaches to the construction of the dihydroxyacetone side chain were
rep~rted.~
Pregenolone
~ ~ J ~ ~ was oxidized with PhIO-KOH-MeOH to the hydroxyacetal(224) which, after acetylation and heating in xylene with toluene-p-sulphonic
acid, gave the acetoxy-enol ether (225). Oxidation (MCPBA) and hydrolysis gave
the required compound (266).lg5The other two routes which started with 17-oxosteroids are outlined, in part, in Schemes 9lQ6and
Tetrazolium salts were
(224)
(225)
(226)
reported to be oxidizing agents suitable for the conversion of 21-hydroxy-20-0~0steroids into the 20-hydroxy- or 20-oxo-21-oic a ~ i d s . 1
~
A~synthesis
was reportedlg9
(Scheme 11) of 1l-deoxyaldosterone from the exo-epoxide mixture (227) which was
ls4
A. Mourifio, S. Lewicka-Piekut, A. W. Norman, and W. H. Okamura, J . Org. Chem., 1980,

45,4015.
R. M. Moriarty, L. S . John, and P. C. Du, J. Chem. SOC.,Chem. Commun., 1981, 641.

D. H. R. Barton, W. B. Motherwell, and S. Z. Zard, J. Chem. SOC.,
1 @ 7 L. Nkdelec, V. Torelli, and M. Hardy, J. Chem. SOC.,
198 M. A. Smoczkiewicz qnd J. Jasiczak, Synthesis, 1980, 739.
lSs M. Miyano, J. Org. Chem., 1981, 46, 1846.
lS5
196
322
Reagents : i, (EtO),POCH(NC)Me-KH ; ii, HCO,H ; iii, Pb(OAc),; iv, pyridinium bromide

perbromide; v, H,O+; vi, KOAc
Scheme 9
{go
OAc
___,
ii, iii
d
iv
Reagents: i, CNCH2C02Et-Bu'OK; ii, LiAIH,; iii, Pb(OAc),; iv, H,O+
Scheme 10
&
($
CH20H ii,iii
i
+
?OH2.-
p,
(227)
1 1-deoxyaldosterone
Reagents: i, LiNEt2-THF; ii, , Ac,O-pyridine ; iii, N-methylmorpholine N-oxide-Os0,Bu'OH-THF-H,O; iv, NaIO,; v, K,CO,
Scheme 11
obtained from the methylene cyclobutane (7).16 The hypoiodite reaction of 20hydroxy-pregnaneswas a key step in the synthesesof 1 8-hydroxycorticosterone200~201
and in the syntheses of 21-deoxy-3a,5~-tetrahydroaldosterone
(228)202and 3a,5p-
2*1
202
D, N. Kiik and C. J. Slade, J . Chem. SOC.,Perkin Trans. 1, 1980, 2591.

D. N. Kirk and C. J. Slade, J. Chem. SOC.,Perkin Trans. I , 1981, 703.
D. R.Crump, D. N. Kirk, and B. W. Miller, J. Chem. SOC.,Perkin Trans. I , 1980, 2597.
323
tetrahydroaldosterone (229).?-03 The 21-hydroxy-compound (229) was obtained

from deprotection of the derivative (231) which was in turn obtained from (230)
by the sequence shown in Scheme 12.
& &[g
Meo
\ OSiMe,
5 (231)
RO-=
(228)
(229)
(230)
(231)
R1= Rz= R3= H

R1= R2= H, R3 = OH
R1= THP, Rz= Me, R3 = H
R1= THP, R2= Me, R3 = OH
Reagents: i, LDA-TMSCI; ii, MCPBA
Scheme 12
The hydroxy-lactone (233) was obtainedzo4by treatment of the 16,17-epoxy-200x0-21-acetate (232) with KOBut. The trifluoroacetoxypregnan-20-ones(234) were
converted into the spirofuranones (235) with DBU in benzene.205The conversion
(232)
of 15a-hydroxy-l l-oxo-progesterone to 3p, 1 1a, 15p-trihydroxypregn-5-en-20-one
has been reported.20s The synthesis of (20R)-5ct-pregn-9(11)-ene-3p,6a,20-triol, a
minor starfish sterol, was reported from ll-oxoprogesterone.zo7A key step in the
synthesis of 10P-ethenyl-hydrocortisoneacetate is the addition of LiC 3 CH to the
5,lO-epoxide (236).208Syntheses of 10-norprogesterone and 19-nordeoxycortiA series
costerone have been reported from 19-norandrost-4-ene-3,17-dione.z09
of hormonally active D-homopregnanes has been synthesized210 and c-homo20a
204
D. N. Kirk and B. W. Miller, J. Chem. Soc., Peikin Trans. I , 1980, 2818.

K. AMen, H. Hofmeister, H. Laurent, K. Petzdolt, A. Seeger, and R. Wiechert, Chem. Ber.,
1980,113,3827.
G. Ortar and E. Morera, J. Org. Chem., 1981, 46,452.

G. R. Weihe and T. C. McMorris, Steroids, 1981,37,291.
207 J. W. ApSimon, S. Badripersaud, J. A. Buccini, J. Eenkhoorn, and M. W. Gilgan, Can. J.
Chem., 1980,58,2703.
208 G. Teutsch and C. Richard, J. Chem. Res. (S), 1981, 87.
209 C.-Y. Byon and M. Gut, J. Org. Chem., 1980, 45,4403.
210 M. Muller, L. Alig, P. Keller, A. Furst, U. Kerb, and R. Wiechert, Web. Chim. Actu, 1980,63,
206
20*
1867.
324
(236)
compounds were obtained from hecogenin, the ring expansion being achieved by a
Demjanov reaction on the 12-aminomethyl-12-hydro~y-derivative.~~~
12 Androstanes and Oestranes

The Claisen rearrangement of the A5-vinyl ether (237) provided the aldehyde (238)
which was modified to give the ethynyl derivative (239) and the allene (241) was
prepared from the acetoxy-ethynyl derivative (240) through a mixed cuprate-
e o
hP
mediated reductive elimination.212Further studies were reported in the preparation

of D-nor-androstanes from p,y-unsaturated diazoketones in the d i t e r p e n e ~ A
.~~~
number of 4,5-seco- and ~-nor-3,5-seco-androstanes
were ~ynthesized.~l*
An extension was reported215of the preparation of 11p-substituted compounds
(242) through reaction of A9 (11)-5,10-epoxides with lithium organocuprates.216A
212
G. Haffer, U. Eder, G. Neef, G. Sauer, and R. Wiechert, Annulen, 1981, 425.

B. W. Metcalf, C. L. Wright, J. P. Burkhart, and J. 0.Johnston, J. Am. Chem. SOC.,1981,103,
213
P. Ceccherelli, M. Curini, M. Tingoli, and R. Pellicciari, J. Chem. SOC.,Perkin Trans. 1, 1980,
211
3221.
1924.
214
216
A. Kasal, Collect. Czech. Chem. Commun., 1980, 45, 2541.

A. Belanger, D. Philibert, and G. Teutsch, Steroids, 1981, 37, 361.
325
synthesis of 16a-hydroxy-~-nor-5a-oestran-2-one
involved regioselective hydroboration of a AIG-derivativewith di-isoamylborane.216
The synthesesof 1l-hydroxy9a- and -9p-oestrones were reported217and an investigation into stereoselective
routes to 14,15,17-trisubstituted oestra-l,3,5(10)-trienes from the A14-compounds
demonstrated that both the 17@-acetoxy-14a,l5a-epoxideand its 14@,15@-epimer
gave largely the 14p-15-oxo-compound.218
Oestriol 16-glucuronidewas synthesized
through reaction of 2,4-dibromo-16a-hydroxyoestrone with methyl l-bromo-ldeoxy-2,3,~-tri-~-acety~-a-~-pyranosuronate.~~~
13 Cardenolides
Further studies in the synthesis of 14-deoxy-14a-strophanthidinwere reported.220v221

A new synthesis of 15-hydroxy-cardenolidesinvolved the addition of 2-methoxy-4fury1 lithium to A 1 5 - 1 7 - ~ ~ ~ - ~ ~asmap key
~~n
step.222
d ~ A novel approach to
cardenolides from 17-0x0-steroids is outlined223in Scheme 13. Anhydroxysmalo-
+
vi
vii, viii
Reagents: i, NCCH,CO,Et-base; ii, NaBH,; i i i ,

vii, SOC1,-pyridine; viii, Li,CO,-DMF
I -H+; iv Bu',AlH; v, HCN; vi, HCI;
Scheme 13
genin was
from the A5~14-diene-20-oxo-compound
(244) which was
obtained from the enone (243). An improved synthesis225of 14p-hydroxy-cardenolides from the A 1 4 - ~ ~ m pinvolved
~~nd~
sequential reaction with NBA and Bu3SnH.
Syntheses of the saturated lactones (245)226and their a,@-unsaturatedanalogues227
21@
21*
$lQ
220
221
222
233
224
aa6
J. Canceill and J. Jacques, Bull. SOC.Chim. Fr., 1980, 468.

R. B. Gabbard, L. F. Hamer, and A. Segaloff, Steroid, 1981,37,243.
J. R. Bull and J. Floor, J. Chem. SOC.,Perkin Trans. I , 1981, 437.
M. Numazawa, M. Nagaoka, M. Tsuji, and Y .Osawa, J. Chem. SOC.,Chem. Commun., 1981,
383.
P. KoEovskg, Collect. Czech. Chem. Commun., 1980, 45,2998.
R. Marini-Bettolo, P. Flecker, T. Y. R. Tsai, and K. Wiesner, Can.J. Chem., 1981, 59, 1403.
A. Kurek, M. Gumulka, and J. Wicha, J. Chem. SOC.,Chem. Commun., 1981, 25.
P. KoEovskY and V. Cerny, Collect. Czech. Chem. Commun., 1981,46,446.
C. R. Engel and D. Mukherjee, Steroid, 1981, 37, 73.
V. Pouzar and M. Havel, Collect. Czech. Chem. Commun., 1981,46, 107.
V. Pouzar and M. Havel, Collect. Czech. Chem. Commun., 1981, 46, 917.
12
326
and of the methylene lactones (246)226were reported. Methylation of digitoxigenin

led228to the cardenolides (247)-(250) and the syntheses of the y-steroidyl buten-
6'.
{
(247)
(248)
(249)
(250)
OH
R1= H, R2= p-Me

R1 = H, R2= a-Me
R1 = Me, R2 = H
R1 = Me, R2 = Me
(251)
(252)
(253)
(254)
R' = R2 = H, 20p-H
R1 = R2 = H, 20a-H
R1 = Me, R2 = H
R1 = H, R2 = Me, 203-H
olides (25 1)-(254) were reported.229The p-steroidyl crotonate methyl esters (255)
and (256) were synthesized from the 14~-hydroxy-20-oxo-compound.230
kCHC02Me
3-OAc
220
230
\ ,.CHCO,
C. Lindig and K. Kepke, J. Prakt. Chem., 1980, 322,991.

F. Theil, C. Lindig, and K. Repke, J. Prakt. Chem., 1980, 322, 1003.
F. Theil, C. Lindig, and K. Repke, J. Prakt. Chem., 1980, 322, 1012.
327

14 Heterocyclic Steroids
Reaction of 2a,3a-epoxy-5a-androstanewith CF3C02H and the thiazolidine-2thione (257) gave 2@,3f~epithio-Sa-androstane.~~~

The reactions of 2-aminobenz-
U k S
NH
-.
(257)
(258)
imadazole with 2-hydroxymethylene-3-oxo-androstanes

were reported232to give the
pyrimidobenzimidazoles (258). The reaction between 2-mercaptoimidazole and
2a-bromo-5a-cholestan-3-one in ethanol gave the imidazothiazole (259) and the
ethanol adduct (260) and similar reactions were observed with 2-mercaptobenzimidazole and 3-rnercapt0-1,2,4-triazole.~~~
Similar reactions occurred between
(259)
(260)
16a-bromo-oestrone methyl ether and 3-mercapto-1,2,4-triazole and its 5-methyl
derivative, but with 2-mercaptoimidazole simple displacement of the bromine was
observed. In NaHC0,-DMSO, 16a-aminomethyl- and 16a-benzyIarninomethy13-methoxy-17~-tosyloxyoestra-l,3,5(10)-trieneunderwent cyclization to the
tetrahydro-oxazin-2-ones(26 1) and (262) respectively.234Tomatidine was converted
into the (22S,25S)-N-methyl-derivative
stereospecifically,whereas solasodine led to
and the (22S,25R)-N-methyl-deriva mixture of the (22RY25R)-N-methyl-derivative
a t i ~ e .Treatment
~~~
of 17p-acetoxy-17a-ethynyl-steroids with NOF-NOBF,
gave236the diacylfuroxans (263) which on thermolysis gave the acylnitrile oxides
(264) which could be trapped with suitable d i p o l a r o p h l e ~ A
, ~ ~synthesis
~
of
26-(3-methylindol-l-yl)cholesterolwas
Hexachlorotriphosphazene was
to react with a variety of steroidal alcohol sodium salts to give the
substituted derivatives (265). Organopalladium complex-catalysed coupling of
acetylenic organozincs with 5-iodo-3,5-0-bis(trimethylsilyl)deoxyuridinegave
5-alkynyl-2-deoxyuridinesand was exemplified by the preparation of the steroidal
example (266).240
R. C. Cambie, G. D. Mayer, P. S. Rutledge, and P. D. Woodgate, J. Chem. SOC.,Perkin
Trans. 1, 1981, 52.
232 J. S.Bajwa and P. J. Sykes, J. Chem. SOC.,
Perkin Trans. 1, 1980, 1859.
2S3 J. S. Bajwa and P. J. Sykes, J . Chem. SOC.,Perkin Trans. 1, 1980, 2146.
234 G. Schneider, L. Hackler, and G. Dombi, J. Chem. SOC.,Chem. Commun., 1980, 891.
235 H. E. Gottleib, I. Belic, R. Komel, and M. Mervic, J. Chem. SOC.,
236 D.R.Britteli and G. A. Boswell Jr., J. Org. Chem., 1981, 46, 312.
237 D.R.Britteli and G. A. Boswell Jr., J . Org. Chem., 1981, 46, 316.
2s8 T. Arunachalam, P. J. MacKouI, N. M. Green, and E. Caspi, J. Org. Chem., 1981, 46,2966.
239 H.R.Allcock, T. J. Fuller, and K. Matsumura, J. Org. Chem., 1981,46, 13.
240 P. Vincent, J.-P. Beaucourt, and L. Pichet, Tetrahedron Lett., 1981, 22,945.
231
328
(261) R
(262) R
CH,Ph
C1 O-Steroid
deoxyribose
I
CI-P,
/ N
c1
P-Cl
Me0
15 Microbiological Reactions
Further studies were r e p ~ r t e d ~on

~ lthe
? ~degradation
~~
of deoxycholic acid with
Pseudoinonas species. Side chain-degraded products, for example the hydroxydiene-dione (267), appeared to be important. Digoxin was reported as the main
degradation product from Streptomyces mediated modification o f d i g i t o ~ i n . ~ 4 ~
Other products were 7p-hydroxydigitoxin and 7P-hydroxydigoxin. .Microbial

transformation of [ 16~-~H]-precursors
gave [16~-~H]androstenedione
and [16ce3H]o e ~ t r a d i o lIt. ~was
~ ~reported that Tenebrio molitor was able to convert the 24R,28Sisofucosterol epoxide into cholesterol more readily than the 24S,28R-isomer,
whereas no significant difference was observed for the reactivities of the 24,213fucosterol e p o x i d ~ sIncubation
.~~~
of phytosterol mixtures with a mutant strain of
Mycobacterium fortuiticrn resulted246in the accumulation of novel 24-oxo-steroids
L41
242
243
?44
245
246
R. A. Leppik, Tetrahedron, 1981, 37, 1747.

R. F. Bilton, A. N. Mason, and M. E. Tenneson, Tetrahedron, 1981,37, 2509.
Z. Szeleczky, M. Soti, G . Horvith, and K. Albrecht, Steroids, 1981,38, 11.
R. Cantineau, P. Kremers, J. De Graeve, A. Cornelis, P. Laszlo, J. E. Gielen, and R. Lambotte,
Steroids, 1981, 37, 177.
F. Nicotra, P. Pizzi, F. Ronchetti, G. Russo, and L. Toma,J. Chem. Soc., Perkin Trans.I, 1981,
480
J. C. Knight and M. G. Wovcha, Steroids, 1980, 36, 723.
329
for example (268) (269). An aerobic, concentration dependent, reduction of

A4-3-oxo-androstanes and -pregnanes to the 5 P-3-oxo-analogues was reported with
Clostridium paraputrifactum. 247 The thermophilic bacterium Caldariella acidophila
was reported to convert progesterone into a number of 6-oxygenated derivati~es.~4*
Hydroxylation of B-nortestosterone and related compounds with Rhizopus arrhizus
ATCC11145 gave a product range which suggested that the stereochemistry of
oxidation at C-6 was controlled by stereoelectronic effects in the substrate.249
[3-180]Testosterone was reported to be transformed to oestradiol by human
placental microsomes and to the 68- and I 1P-hydroxy-derivatives by Rhizopus
arrhizus without significant loss of the oxygen label, suggesting that neither process
involves reversible Schiff base formation at C-3.250The major products from
incubation of androst-4-enes and androst-5-enes with Cunninghamella elegans
arose from allylic
and those from Sa-androstan- 17-oneswere reported252
to arise from 1 p,7-dihydroxylation or 7-hydroxylation. Under similar conditions,
17a-aza-~-horno-5a-androstan17-ones underwent monohydroxylation at positions
6p-, 7a-, or 9a- dependent upon substituents at C-3.252
24i
248
240
250
251
2j2
A. Fauve and A. Kergomard, Tetrahedron, 1981, 37, 899.

M. De Rosa, A. Gambacorta, G . Sodano, and A. Trabucco, Experientia, 1981, 37, 541.
H. L. Holland, Can. J. Chem., 1981, 59, 1651.
H. L. Holland and G . J. Taylor, Can. J . Chem., 1980, 58, 2326.
T. A. Crabb, P. J. Dawson, and R. 0. Williams, J . Chem. SOC.,Perkin Trans. I , 1980, 2535.
T. A. Crabb, J. A. Saul, and R. 0. Williams, J. Chem. SOC,Perkin Trans. I , 1981, 1041.
Author Index
Abdel-Magid, A., 310
Abdel Salam, N. A,, 102
Abe, F., 59
Abe, H., 312
Abe, K., 266
Abiko, A., 29, 79
Abraham, W.-R., 75, 174
Abryutina, N. N., 286
Abubakirov, N. K., 234
Accrombessi, G., 39
Achari, B., 172
Acharya, S. P., 6
Achenbach, H., 58
Acklin, G., 304
Acton, N., 249
Adam, G., 198
Adam, W., 38
Adams, R. P., 73
Addae-Mensah, I., 58
Adesogan, E. K., 59, 60
Adesogan, K. A., 189
Adinolfi, M., 21 1
Adlercreutz, H., 281
Adolf, W., 200
Adriani, C., 59
Afifi-Yazar, F. U., 5, 59
Agami, C., 298
Agarwal, P. K., 115
Agarwal, S. G., 211
Ager, D. J., 34
Ageta, H., 225
Aggarwal, R. C., 39
Agosta, W. C., 25
Agurell, S., 66
Ahem, D. G., 254
Ahmad, I., 174
Ahmad, M. S., 307
Ahmad, V. U., 225
Ahmed, M., 88, 111, 115,
146,156,169,188,189,196
Ahmeij, M., 66
Ahn, B. Z., 59
Ai, T.-H., 215
Aimi, N., 232
Akelah, A., 288
Akhila, A., 39, 68
Akhmetov, L. I., 12, 48
Akimaliev, A. A., 234
Akimoto, K., 135
Akinniyi, J . A., 146, 216
Akita, H., 85, 193, 194, 259
Akiyama, T., 60, 61, 215,
277
Akporiaye, D. E., 303
Akutogawa, S., 42
Alazard, J.-P., 303

Albert, K., 146
Alberte, R. S., 239
Alberti, A., 7
Alberts, V., 38
Albone, K. Y. S., 197
Albrecht, K., 328
Albrecht, P., 225
Albini, A., 309
Alcaide, B., 278
Alder, A. P., 255
Alderice, M., 31
Al-Ekabi, H. K., 198
Alfano, R. R., 259
Ali, H., 284, 307
Ali, S. M., 299
Alibaeva, Kh. A., 230
Alig, L., 323
Alimbaeva, P. K., 234
Allan, A. E., 257, 259
Allcock, H. R., 327
Allen, M. S., 45, 48
Alper, H., 46, 302
Alshuth, T., 258
Alvarez, R. A., 255
Amico, V., 186, 201
Amin, B., 246
Amiya, T., 115
Amouroux, A., 27
Anandaraman, S., 42
Anastasia, M., 312
Andenaert, F., 39
Anding, C., 207
Anding, C. R., 317
Ando, M., 157
Andreetti, G. D., 61
Andreis, P., 45
Andrews, G. C., 45
Andrianov, V. G., 6
Andrieu, C. G., 4, 5
Andrus, A., 205
Anglister, J., 258
Anjaneyulu, A. S. R., 214,
226,230
Ankudinova, T. V., 255
Annen, K., 323
Annis, G. D., 129,295
Ansell, M. F., 52
Antbarjanam, T. G. B., 18
Antipin, M. Ya., 272
Antkowiak, R., 45
Antkowiak, W., 45
Anufriev, V. F., 216
Aoki, S., 19, 62
Aoki, T., 72, 234
w.,
252
Appeldoorn,
ApSimon, J. W., 228, 323
Aragon, C. M. G., 262
Aranda, J. C., 204
Arata, K., 37,42, 51
Aratani, T., 40, 89
Arbuzov, B. A., 43, 5 5 , 56,
57
Argade, P. V., 258
Argyriadou, N., 44
Arigoni, D., 140, 209
Arita, M., 31, 264
Ariwa, M., 176
Arlt, D., 61
Amaboldi, M., 247, 260
Arnold, E. V., 196
Arnoux, B., 219
Arora, A. K., 14
Aruldhas, G., 278
Arunachalam, T., 327
Arvidson, G., 258
Asakawa, Y., 73, 8 5 , 158,
172, 183, 184
Asano, S.,62
Ashref, M., 31
Aslanov, K. A., 188
Atal, C. K., 15, 33, 211
Atimoshone, M. V., 195
Atkinson, G. H., 257
Atopkina, L. N., 216
Atsumi, K., 183
Attwell, M. C., 271
Atwal, K. S., 3 11
Audenaert, F., 178
Aulchenko, I. S., 20, 34
Avery, M. A., 60, 99
Avetisyan, G. M., 230
Aviv, D., 72
Ayafor, J. F., 221
Ayengar, K. N. N., 228
Ayer, W. A., 124, 127, 128,
131, 134, 202
Baas, P., 255
Babin, D., 16, 39, 64, 89
Babler, J. H., 25, 64
Bachner, J., 47
Back, T. G., 302
Baddeley, G. V., 21 5
Badripersaud, S., 323
Badruddoza, S., 193
Bagan, E., 291
Baggiolini, E. G., 318
Bailey, T. R., 42, 297
33 1
Author Index
Bailleul, F., 58, 59
Baines, D. A., 55
Bajwa, J. S., 327
Baker, P. M., 215
Baker, R., 23, 77, 81
Bakunin, V. N., 49, 51
Bakuzis, M. L. F., 43
Bakuzis, P., 43
Bal, B. S., 24, 36, 38
Balashov, S. P., 259, 260
Balasubramanian, V., 308
Balci, M., 32
Baldwin, J. E., 91
Baldwin, S. W., 60
Balliano, G., 215
Balogh-Nair, V., 247, 259,
260
Balsevich, J., 54, 160
Bambagiotti, A. M., 5
Band, P. R., 255
Bandrauk, A. D., 257
Banerjee, A. K., 204
Banerjee, D. K., 270, 271
Bang, L., 21 1
Banks, R. E., 98
Bano, S., 225
Banou, T., 14
Bansal, R. K., 192
Banthorpe, D. V., 4, 13, 39,
63,68
Bapuji, M., 158
Baragliu, A., 37
Barany, F., 25
Baranyai, M., 256
Barba, R., 45
Barbara, P. F., 259
Barden, T. C., 91
Bardyshev, I. I., 45, 5 5
Barer, D. G., 42
Bari, S. S., 18, 206
Barker, A. J., 105
Barkhan, P., 266
Barnard, G., 285
Barner, R., 269, 318
Barnett, R., 255
Barnette, W. E., 43
Barrero, A. F., 48, 118
Barrett, A. G. M., 292, 301,
302
Barrick, R. C., 232
Barron, L. D., 5
Barros Papoula, M. T., 296
Barrow, S. E., 13
Barth, G., 51, 52
Bartlett, A. J., 87
Bartlett, P. A., 27, 34
Barton, D. H. R., 35,37,213,
292, 296, 299, 301, 302,
321
Barua, A. B., 263
Barua, A. K., 187,226, 230
Baruah, R. N., 146
Basak, A., 187, 227
Bateho, A. D., 312
Bates, P., 15
Bates, R. B., 219
Battaglia, R., 135
Battalova, S., 49
Battegay-Nussbaumer, Y .,
243
Battersby, A. R., 70
Bax, A., 274
Baxter, R. L., 86
Bayley, H., 260
Bazylchik, V. V., 13, 33
Beal, J. L., 4
Beale, M. H., 198, 228
Bearder, J. R., 198
Beaucourt, J.-P., 327
BeauLaire, J., 174
Beaulieu, P., 21
Beaupin, C., 60
Becchi, M., 280
Beck, J.-P., 211
Becker, J. J., 51
Becker, R. S., 258
Bedi, A. L., 21, 39
Bedour, M. S., 277
Beecham, A. F., 277
Begley, M. J., 146
Begue: J. P., 9
Beier, R. C., 106
Bekhtereva, M. N., 261
Bekker, A. R., 247
Belanger, A., 324
Belanova, E. P., 33
Beletskaya, I. P., 49, 51
Belic, I., 327
Bell, A. A., 106
Bell, K. H., 46
Bellesia, F., 61
Bellido, I. S., 32
Bellus, D., 64
Beloeil, J.-C., 270, 297
Belousova, L. I., 46
Below, P., 33
Belozerskaya, T. A., 262
Belyaeva, M. E., 55
Ben-Ari, C., 276
Benayoun, J., 74
Bendall, M. R., 58, 60
Benezva, C., 318
Benko, A. B., 283
Bennett, N., 259
Bennett, R. D., 221
Bensasson, R. V., 243
Bensel, N., 11
Bentley, R., 266
Benveniste, P., 210
Ben-Zvi, Z., 66
Berbalk, H., 318
Berg, D., 283
Berger, D. E., 312
Berger, Y., 208
Bermejo, J., 146
Bernard-Dagan, C., 4, 74
Bernardini, A., 114
Bernasconi, S., 184, 194
Bernays, E., 57
Bernhard, K., 237, 240
Berry, R. A., 261
Berti, C., 52
Bertran, J. F., 5
Bertrand, C., 42
Bertranne, M., 270, 297
Besai, D. N., 39
Besner, J. G., 255
Bessiere, Y., 3
Best, W. M., 110
Bestmann, H. J., 249
Betancor, C., 226
Bettolo, R. M., 61
Bevelle, C. A., 146
Beydon, P., 282
Beyer, P., 261
Bezzubov, A. A., 256
Bhadbhade, M. M., 193,271
Bhagwat, S. S., 121
Bhardwaj, T. R., 271
Bhat, N. E., 55
Bhat, N. G., 57, 64
Bhat, U. G., 146
Bhatt, M. V., 300
Bhatta, A. K., 312
Bhattacharyya, S. C., 65, 66
102, 104
Bhatty, M. K., 31, 174
Bialer, M., 307
Bianco, A., 5, 58, 59, 60, 61
Biedrzycki, H., 10
Bierl-Leonhardt, B. A., 7,63
Biggs, R. H., 254
Biguet, J., 172
Bikbulatova, G. S., 56, 57
Billington, D. C., 77
Bilton, R. F., 328
Binder, M., 65, 73
Biran, C., 10
Birch, A. J., 6, 44
Birch, A. M., 138
Bird, T. G. C., 101
Birge, R. R., 259
Bishop, R. D., 12
Biswas, S., 187
Bjoroy, M., 232
Black, B., 47
Blackwell, D. S. L., 53
Blais, C., 282
Blanc, P. A., 312
Blanco, L., 63, 88
Blazejewski, J.-C., 292, 296
Bledsoe, J. O., 38
Blinova, V. A., 6
Blosczyk, G., 226
Blount, J. F., 143, 146, 174,
200, 202,311, 318
Blum, M. S., 60
Blunden, G., 279
Blunt, J. W., 194
Blunt, R. W., 15
Bluthe, N., 50
Bobrowski, K., 251, 259
Author Index
332
Boccalotte, A., 69
Bocelli, G., 61
Bodea, C., 245
Bodor, N., 275
Boeckman, R. K., jun., 130
Boger, P., 210, 260
Boelens, H., 252
Boeren, E. E., 65
Boettner, F. E., 234
Bohlmann, F., 32,62,66,73,
75, 88, 102, 106, 107, 111,
114, 115, 116, 117, 146,
155, 156, 158, 160, 169,
170, 172, 174, 176, 184,
186, 187, 188, 189, 190,
195,196,225
Bohlmann, R., 67, 116
Bokel, M., 218
Bolard, J., 256
Bolli, D., 58, 59
Bond, F. T., 46
Bondavalli, F., 43, 46
Bonet, J.-J., 310
Bonnet-Delpon, D., 9
Bonini, C., 5 , 59
Borch, G., 237, 238
Borden, W. T., 50
Bordner, J., 205
Borg-Karlson, A.-K., 106
Bori, S. S., 37
Bornack, W. K., 121
Borowiecki, L., 46
Borschberg, H. J., 45
Borthakur, N., 146
Bose, A. K., 60, 280
Bosshardt, M., 35
Boswell, G. A., jun., 327
Botten, J. A., 28
Boucher, F., 259
Bouchier, I. A. D., 291
Bouchisic, B., 51
Boulton, K., 199
Bourgeay-Causse, M., 255
Boussac, G., 31, 82
Bouvier, P., 208, 209
Bowden, B. F., 172,182,200
Bowen, J. M., 278
Boya, M. T., 193
Boyd, J. D., 38
Boyd, R. K., 5
Boyer, J., 40
Brabham, D. E., 254
Bradshaw, A. P. W., 140
Braekman, J. C., 114, 202
Brahmana, H. R., 243
Braiman, M., 258
Bramley, P. M., 261
Branca, S. J., 63
Brand, J. M., 60
Brand, M., 41
Brandange, S., 8
Brangeon, J., 260
Braz Filho, R., 190
Bregovec, I., 76
Brendolan, G., 194

Breuer, A., 62
Breuer, E., 3 18
Brianso, J. L., 310
Brianso, M. C., 310
Brich, Z., 44
Brickner, S. J., 161
Bricout, J., 72
Bridges, C. D. B., 255
Brieger, E., 42
Brieskorn, C. H., 54, 226
Brion, F., 63
Britteli, D. R., 327
Brocksom, T. J., 36, 37
Broek, A., 258
Broek, A. D., 246
Bronneke, A., 40
Brooks, C. J. W., 281
Brooks, C. T., 287
Brookhart, T., 312
Brosche, T., 54
Brossi, A., 249
Brown, D. S., 306
Brown, D. W., 275
Brown, F. J., 278, 280
Brown, H. C., 51, 52, 115
Brown, J. D., 67
Brown, K. H., 38
Browne, E. N. C., 114
Browne, L. E., 70
Browne, L. M., 124, 202
Briiggemann-Rotgans,
I. E. M., 77
Bruins, A. P., 280
Brun, P., 5
Buccini, J. A., 323
Buchbauer, G., 47, 48
Buchecker, R., 237
Buchectar, C. D., 64
Buchs, A., 280
Budai, D., 61
Budzikiewicz, H., 44,59,62
Biichi, G., 23, 39, 46
Buinova, E. F., 55
Bull, J. R., 325
Bunton, C. A., 28
Burak, K., 49
Burbott, A. J., 72
Burger, U., 14
Burgstahler, A. W., 160
Burinato, C., 223
Burke, B. A., 193, 200,
202
Burke, M. C., 45
Burkhart, J. P., 324
Burlage, U., 73
Burnell, R. H., 193
Burreson, B. J., 200
Burshtein, L. L., 286
Burton, L. P. J., 83
Busetta, B., 271
Bushey, D. F., 205
Butler, I. S., 275, 276
Byon, C.-Y., 277, 323
Caballero, E., 48
Cagnoli-Bellavita, N., 192,
194
Cahiez, G., 29
Caine, D., 164
Cainelli, G., 3, 239
Cairns, J., 297
Calas, R., 10, 25, 51
Cole, W. J., 281
Callahan, J. F., 107,143, 155
Callant, P., 61
Callender, R. H., 258, 259
Calzadilla, C. H., 85, 86
Camara, B., 260
Cambie, R. C., 292,302,327
Campanelli, A. R., 278
Campbell, I. M.,85
Campbell, M. M., 298
Camps, F., 192
Canceill, J., 325
Cane, D. E., 70, 88, 98, 129,
194
Cane, O., 4
Cano, G., 158
Cannistraro, S., 259
Cannon, J. R., 226
Canoras, A., 310
Cantineau, R., 328
Capdevielle, P., 49
Capomacchia, A. C., 256
Capon, R. J., 15, 17
Caporusso, A. M., 13
Capp, M., 281
Caputo, O., 215
Cardenas, C. G., 38, 45
Cardillo, G., 3, 239
Cariello, L., 239
Cargill, R. L., 205
Carlsen, P. H. J., 27
Carlsen, W., 258
Carlson, R. M. K., 282
Carman, R. M., 38, 41, 46,
47,195,213
Carmely, S., 200,234
Carpenter, R. C., 226
Carr, D., 28
Carr, R. V. C., 21, 36
Carroll, G. L., 139
Carrol, P. J., 104
Caruso, A. J., 81
Casanova, J., 5
Casellato, M., 210
Casida, J. E., 64, 74
Casinos, I., 40
Casinovi, C. G., 37, 223
Caspi, E., 327
Cassady, J. M., 146
Castanet, Y.,48
Castellani, G., 6
Castellano, E. E., 272
Castillo, R., 263
Castognino, E., 31
Castro, A., 284
Castro, V. A., 225
Author Index
Caton, M. P. L., 52
Cattel, L., 215, 234
Cazes, B., 64
Cave, A., 85
Ceccherelli, P., 192, 194,324
Ceolin, R., 272
Cerda-Olmedo, E., 262
Cerfontain, H., 255
Cerny, N. H., 290
Cerny, V., 293, 294, 325
Cerrini, S., 270, 306
Ceskis, B., 16
Chabudzinski, Z., 10,37,40,
49, 50,51
Chadha, N. K., 318
Chakrabarti, P., 270, 271
Chakrabarty, S., 172
Chakravarty, A. K., 277
Chalmers, A. A., 172
Chalmers, W. T., 228
Chambers, D., 302
Chan, D. M. T., 60
Chan, K.-K., 247
Chan, R. L. S., 247
Chan, W. H., 46
Chan, W. R., 200, 202
Chandel, R. S., 207
Chandrasekharan, V., 65,66
Chang, C.-J., 146
Chang, F. C., 312
Chang, H. C., 271, 309
Chang, I.-M., 276
Chang, T. C. T., 35
Chao, P. D. L., 59
Chao, W.-R., 247
Chapman, A. C., 123
Chapman, D. J., 231,261
Charlwood, B. V., 4
Charpentier-Morize, M., 9
Charpiot, B., 292,296
Chastrette, F., 27
Chastrette, M., 27
Chatterjee, S., 23
Chatterjee, T. K., 226
Chattopadhyay, K., 256
Chattopadhyay, S., 234
Chaudhuri, R. K., 5, 7, 58,
59, 60
Chawla, H. P. S., 47, 214
Chayabunjonglercl, S., 99
Chekhlov, A. N., 271
Chekulaeva, L. N., 260
Chen, C. C., 49
Chen, E. Y., 157
Chen, F. H., 196
Chen, S. E., 234
Cheng, Y. S., 35
Chernysheva, E. K., 262
Cheron, M., 256
Chetyrina, N. I., 230
Cheung, H. T. A., 276
Chew, E. 246
Chhabra, B. R., 123
Chiaroni, A., 85
333
Chiba, M., 179
Chichester, C. O., 235, 256
Chien, M. M., 223
Chien, P.-L., 246
Chihiro, M., 223
Childers, W. E., 24, 36
Childs, R. F., 47
Chiu, P. L., 273
Chou, W. H., 196
Choudhury, M. K., 55
Chowdhury, P. K., 146
Chriki, G., 54
Christenson, P. A., 48, 89
Christi, N. H., 31
Christie, J. J., 177
Christou, P. N., 63
Chuiko, V. A., 62
Chuman, T., 264
Chun, M., 246
Chung, S. G., 59
Chytil, F., 250
Cimarusti, C. M., 272, 293
Cimino, G., 79, 298
Ciurdaru, V., 245
Clardy, J., 60, 127, 183, 196,
200, 201, 202
Clark, B. C., 36, 57
Clark, B. P., 5
Clark, R. D., 63
Clark, R. J. H., 258
Clarke, D., 299
Clarke, F. H., jun., 102
Clegg, W., 66
Cliff, G. R., 299
Clive, D. L. J., 21, 38
Clover, M. G., jun., 102
Coates, R. M., 103, 194
Cocker, W., 41, 55
Cohen, N. C., 286
Cohen, T., 39
Coisne, J. M., 228
Cole, J. R., 60, 219
Coleman, J. B., 45
Colin, H., 100
Colin, P., 286
Coll, J. C., 172,182, 192,200
Collera, O., 226
Collins, D. C., 277
Collins, D. J., 295, 318
Collins, M. D., 266
Collins, M. S., 74
Collins, W. P., 285
Comins, D. L., 67
Condran, P., jun., 320
Confalone, P. N., 3 18
Conia, J. M., 63, 89
Conn, R. S. E., 21,48
Conner, A. H., 73, 210, 232
Connolly, J. D., 146, 216,
221
Cooke, R. S., 54
Cookson, A. D., 284
Cookson, R. C., 29, 62
Cooney, J. J., 261
Cooper, A., 257,259

Coran, S. A., 5
Corbet, B., 225
Corde, J. P., 4
Cordell, G. A., 85, 146, 193
Corey, E. J., 25, 53, 204
Cori, O., 4, 28
Cornelis, A., 328
Corrigan, D., 73
Corriu, R. J. P., 40
Corsano, S., 31
Cortel, A., 192
Cortese, N. A., 35
Cossey, A. L., 195, 205
Couffignal, R., 14
Counsell, J. N., 235
Counsell, R. E., 283
Courseille, C., 271
Courtney, J. L., 230
Covey, D. F., 293
Cowall, P. L., 146
Cox, P. J., 146, 169, 271
Cox, R. H., 213
Cox, S. D., 39, 294
Crabb, T. A., 329
Crabtree, R. H., 39, 294
Craig, I. F., 286
Cramer, R., 218, 222
Craveiro, A. A., 190
Craven, B. M., 272,286
Crawford, T. C., 45
Creed, D., 265
Crespi, H. L., 258
Crews, P., 202
Crimmins, M. T., 60
Crist, B. V., 5
Croft, K. D., 202, 234
Crombie, W. M. L., 146
Crombie, L., 10, 22, 64, 146
Crump, D. R., 273
Crone, T. A., 278
Cross, B. E., 194, 195, 198,
199
Croteau, R.,4,35,70,71,72
Crouch, R., 247, 260
Crouch, R. L., 243
Crowley, K. J., 41
Cuatrecasas, J., 114
Cunat, P., 15, 32
Curini, M., 192, 194, 324
Currenti, R., 201
Curry, B., 258
Curry, K. W., 314
Cusanovich, M. A., 256
Czeczuga, B., 238
Dabiri, M., 88
Dabovic, M., 288
Dadoun, H., 303
Dahmen, J., 66
DAlagni, M., 278
Dallinger, R., 257, 259
Daloze, D., 114, 202
Author Index
334
Dalton, J. R., 205
Daly, J. J., 269, 318
Dalzell, H. C., 65, 66
Damtoft, S., 5, 57, 70
Damodaran, N. P., 26
D'Andrea, A., 272
Daniel, T., 265
Danilov, L. L., 264
Danishefsky, S., 100, 121,
135
Dantes, A., 72
Darby, N., 45, 48
Dart, L. L., 263
Darwish, F. A., 223
Das, J., 204
Das, M. C., 230
Das, P. K., 251, 258, 259
Dasgupta, EL, 193
DaSilva, R. S., 19%
DaSilva, J. J., 192
Dastidar, P. P. G., 172
Dastillung, M., 232
Dauben, W. G., 118, 185,
312
Daunis, J., 114
Dauzonne, D., 4
Davydov, V. Y., 282
Dave, V., 276, 307
David, S., 5
Davini, E., 58
Davis, D. L., 253
Davis, R., 289
Dawson, M. I., 247, 250
Dawson, P. J., 329
Day, R. O., 53
Dayal, B., 291, 312
Daza, L. R., 146
De Alvarenga, M. A., 192
De Bernardi, M., 135
De Bianchi, A. G., 238
Declercq, J. P., 6, 114, 202,
228
De Clercq, P. J., 179
De Graeve, J., 328
Degraw, J. I., 246
De Groot, A., 204
Dehennin, L., 281
Deja, I., 110
de Jesus, A. E., 172
Decorzant, R., 23, 179
De Keukeleire, D., 39, 161
Delaris, G., 62
Delaude, C., 226
Delaveau, P., 58, 59
Delay, F., 37
Deleris, G., 10, 51
Delettre, J., 272, 303
Dellers, E. A., 266
Delpech, B., 42
Delprino, L., 234
del Rio, R. E., 115
Deluca, C., 57
DeLuca, H. F., 263,269,319
DeLuca, M., 285
Demailly, G., 34
De Mark, 3. R., 280
Demath, M., 61
de Mayo, P., 53
Dernbitski, A. D., 48, 62
De Miranda, D. S., 194
Demole, E., 23
Denisenko, V. A., 216
Denny, M., 246,250
Dens, N. C., 314
De Pascual Teresa, J., 32,48,
118
Depezay, J.-C., 89
De Rosa, M., 329
De Rosa, S., 79, 298
Derwish, G. A. W., 198
Desage, M., 280
Desai, D. N., 40, 164
Desai, M. C., 214
Descesare, J.-M., 55
Deshchits, G. V., 55
Deshmukh, A. R. A. S., 57,
67
DeSilva, T., 93
De Simone, F., 318
Deslongchamps, P., 45, 166
De Stefano, S., 79, 298
Destro, R., 184
Detty, M. R., 292
Dev, S., 26, 41, 47, 115, 214
Devilbiss, E. D., 7
De Vos, M. J., 64
Devreese, A. A., 179
Dewey, W. L., 66
Dhar, A. K., 88, 116, 146,
158, 172, 187, 188, 189
Dhar, D. N., 193
Dhar, K. L., 15, 33,211
Dhara, K. P., 231
Dhekne, V. V., 67
Diaz, E., 190
Diem, M., 5
Dieter, R. K., 63, 300
Dietsch, A., 234
Diez-Masa, J.-C., 100
Dike, S. Y., 21
Dikstein, S., 51
Dime, D. S., 297
Dimitriadis, E., 75
Din, Z. U., 33, 64
Dinge, A. S., 67
Dini, A., 318
Dinogues, J., 5 1
Dipietro, R. A,, 46
Dirks, G., 243, 256
Ditzel, E. J., 194
Dixon, J., 47
Djerassi, C., 51,52,278,280,
311, 312
Djura, P., 78
Dmitrovskii, A. A., 250
Doddrell, D. M., 274
Doehner, R. F., 41
Doi, E., 34
Dolhyj, S. R., 35
Dombi, G., 327
Dominguez, X. A., 146, 158
Donnelly, D. M. X., 73
Donskova, A. I., 56
Doolittle, R. E., 38
Do Prado, S. K., 196
Dorn, F., 140
Doskotch, R. W., 58
Dougall, D. K., 4
Doukas, A. G., 258,259
Doumas, J., 234
Dovinola, V., 21 1
Draffehn, J., 282
Drage, J. S., 92
Drawert, F., 33
Drebyschak, T. D., 73
Dreiding, A. S., 110, 118
Drengler, K. A., 194
Drief, A., 64
Driessen, R. A., 66
Du, P. C., 321
Duax, W. L., 270, 271
Dubois, G., 85
Dubovenko, Z. V., 73
DUC,D. K. M., 33, 43, 304
Duddeck, H., 277, 298
Duffield, R. M., 60
Duffley, R. P., 65
Dugger, R. W., 253
Duncia, J. V., 61
Dung, J. S., 40
Dunlop, R. W., 15
Dunogues, J., 10, 25, 51
Dupont, A., 114,202
Du Preez, H. E., 62
Durocher, C. K., 281
Duri, Z. J., 198
D'Urso, N. R., 258
Dutta, C. P., 231
Dutta, P. C., 204
Dutta, P. K., 257
Dworan, E., 47
Dyakonova, R. R., 56
Dyer, R. D., 205
Eade, R. A., 225
Ebrey, T. G., 247, 259, 260
Ecoto, J., 50, 100
Ecoto, S. L., 51
Edamura, F. Y., 116
Edenharder, R., 281
Edeny, H., 66
Eder, U., 324
Edgar, M. T., 52
Edwards, 0. E., 47
Eenkhoorn, J., 323
Egger, J. C., 32
Eguchi, T., 269
Eguren, L., 191
Egyed, O., 278
Ehrenberg, B., 258
Eichinger, K., 318
335
Author Index
3gendorf, G., 210
Zilerman, R. G., 166
Zkanayake, N., 77
Zlder, J. W., 47
3lgama1, M. H. A., 277
Zliel, E. L., 44
Zlizalde Gonzalez, M., 282
Zllerbrock, B. H., 266
Zlliott, W. H., 281
Zllis, A. B., 258
Sllis, J., 225
Zllis, P. R., 241
Zllison, B. O., 73
Zl-Naggar, L. J., 4
Slnaggar, S. R., 58
3-Sayed, M. A., 258
Zl-Sebakhv. N. A.. 195
Elsohly, M: A., 65, 66, 70,
174
Elvidge, J. A., 15
Emanuel, N. M., 245
Emanuelson, I., 73
Emelyanov, M. M., 33, 252
Emmer, G., 221
Encarnacion, R., 234
Endo, T., 32, 59
Engel, C. R., 325
Engel, L., 14
Enggist, P., 23
England, B. G., 283
Englert, G., 255
Enriquez, R., 103
Ensley, H. E., 36
Epstein, W. W., 62
Erasmuson, A., 195, 199
Erickson, E. W., 44
Eridente, A., 69
Erm, A., 15
Erman, M. B., 20, 34
Ernst, L., 48
Eschenmoser, A., 209
Escher, S., 32, 51, 231, 238
Escoffier, A., 260
Eshhar, Z., 285
Eskins, K., 255
Esposito, P., 58
Esvelt, R. P., 319
Etheredge, S. J., 135
Etoh, H., 14, 252
Eugster, C. H., 193, 237
Eyring, G., 258
Ezaki, Y., 241
Fadlallah, M., 298

Fales, H. M., 60
Fang, J.-M., 179
Fardella, G., 223
Fargerlund, J., 63
Farina, V., 21
Farnsworth, N. R., 85, 146
193
Farrant, R. D., 303
Farrell, I. W., 140
Faruk, A. E., 241

Fatturusso, E., 201
Faulkner, D. J., 75, 78, 202,
238
Faust, Y., 42
Fauth, D. J., 38, 255
Fauve, A., 299, 329
Fayos, J., 190, 191, 192
Fedeli, W., 270, 272, 306
Fedorov, P. I., 13, 33
Feigenson, G. W., 266
Felton, M., 71
Fenical, W., 31, 183, 188,
201,202
Feofilova, E. P., 261
Ferber, G. J., 28
Ferguson, G., 85
Fernandez, F., 278
Ferraboschi, P., 295
Ferrari, M., 184
Ferreira, C., 238
Ferreira, J. T. B., 36, 37
Ferrino, S., 207, 223
Fetizon, M., 33,50, 100,270,
297,303,304
Feuerstein, I., 62
Feuillerat, G., 6
Fiand, J. C., 11, 43
Ficini, J., 64, 101
Fiecchi, A,, 312
Fiedler, L., 184, 188
Fielden, R., 46
Fields, K. W., 45
Fiksdahl, A., 237
Filer, C. N., 254
Filippone, P., 195, 199
Filippova, T. M., 247
Finamore, E., 318
Findlay, J. A., 39, 164
Findlay, J. N., 40
Finer-Moore, J., 200
Finkelshtein, E. I., 251
Finner, E., 5, 59
Firth, M. R., 194
Fischer, E., 309
Fischer, N. H., 146
Fischli, A., 13
Fish, R. H., 70
Fitch, F. M., 12
Fitzpatrick, F. A., 281
Fitzsimmons, B. J., 64
Firizzani, M. A., 319
Fkih-Tetouani, S., 114
Flecker, P., 325
Fleming, I., 19, 34
Fleming, M. P., 5
Floor, J., 325
Folefoc, G., 27
Fong, S.-L., 255
Fonrodona, J., 310
Foote, C. S., 38
Ford, C. W., 58, 60
Ford, J., 285
Ford, T. M., 51
Forgacs, P., 234

Forn, B., 74
Forni, A., 5
Forster, R. W. G., 306
Foss, P., 238
Fouchet, B., 44
Foulkes, J. A., 284
Fourneron, J.-D., 16,39,64,
89
Fournet, A., 156
Fourrey, J. L., 174
Fox, M. A., 49
Fraga, B. M., 192, 195, 198,
199,230
Francesconi, A., 60
Francke, W., 28
Franck-Neumann, M., 63,
64
Franco, R., 146, 158
Frank, A. W., 31
Franke, C. S., 53
Franke, I., 65
Frank-Kamenetsky, M. D.,
257
Fransen, M. R., 246, 258,
259
Frappier, F., 276
Fraser-Reid, B., 64, 93
Frater, G., 42
Frazier, K., 98
Frazier, R. H., 40
Freedman, T. B., 257
Freeman, R., 274
Freer, A. A., 193
Frei, B., 255
Freire, R., 226
Frenkiel, T. A., 274
Frey, H., 249
Friedman, A. L., 239
Friedman, L., 37
Friedrich, E., 36
Friedrich, K., 52
Friemann. J., 181
Friguelli, R., 31, 252
Frimer, A. A., 64
Frincke, J. M., 160
Fristad, W. E., 42, 297
Fritz, G., 172
Fritz, U., 62, 116, 146, 169
Frohlich, T., 181
Frolik, C. A., 263
Fronza, G., 135
Frost, D. C., 7
Frot-Coutaz, J., 256
Fry, A. J., 49
Fry, J. L., 53
Fuchida, M., 210
Fuchs, W., 225
Furst, A., 290, 323
Fuhrer, H., 272, 273, 289
Fuji, K., 186, 190, 196
Fujihara, Y., 24, 35, 42, 51
Fujimori, T., 163, 238
Fujisawa, T., 9, 39
Author Index
336
Fujita, E., 186, 190, 196
Fujita, T., 11, 21, 60, 197
Fujita, Y., 265
Fujiwara, H., 60, 280
Fujiwara, T., 165
Fukamija, N., 40, 89
Fukumoto, K., 27, 80, 223
Fukunaga, Y., 31, 263, 264
Fukungaga, T., 41
Fukushima, H., 234
Fukuzawa, A., 99
Fuller, T. J., 327
Fung, S., 316
Fung, V. A., 247
Furukawa, H., 146, 174
Furusaki, A., 99, 124, 157,
199,306
Fusaka, T., 165
Fusitani, M., 33
Gabbard, R. B., 325
Gabke, S. Y., 45
Gadwood, R., 121
Gaertner, W., 259, 260
Gagarina, A. B,, 245
Gage, D., 174
Gal, C., 42
Galdecki, Z., 55
Galindo, A,, 158
Galum, E., 72
Gambacorta, A., 329
Gambliel, H., 71
Ganguly, J. K., 231
Ganguly, R. N., 104
Cannon, M., 50
Garbers, C. F., 62
Garcia, C., 225
Garcia, G. A., 15
Garcia-Alvarez, M. C., 187,
188, 190, 192, 225
Garcia-Fraile, A., 47
Garcia-Granados, A., 199
Garcia-Martinez, A., 47
Garcia-Rodriguez, M. J., 72
Gardlik, J. M., 46
Gariboldi, P., 184, 194
Garnero, J., 31
Garti, N., 271
Garyanov, R. Kh., 230
Garzez, W. S., 192
Gasa, S., 199
Gase, R. A., 296
Gasic, M. J., 288
Gaskin, P., 197, 198
Gatilov, Y. V., 200
Gatuma, A. K., 146
Gaudioso, L. A., 62
Gaughan, L. C., 64, 74
Gaughan, R. G., 63
Gautier, B., 256
Geenevasen, J. A. J., 255
Gelbaum, L,. T., 102
Gemal, A. L., 13
Gendin, D. V., 46
Geneste, P., 39
Gen&t,J. P., 64, 101
Geoffre, S., 271, 272
Gerder, J. M., 306
Germain, G., 6, 114, 202,
228
Geroghty, N. W. A., 55
Gerr, R. G., 272
Gerstenberger, M. R. C., 288
Gerval, J., 10
Gerwick, W. H., 202
Ghaffiari, M. A., 307
Ghisalberti, E. L., 15, 78,
104, 186, 189, 202
Ghosal, S., 234
Ghosh, A,, 230
Ghosh, P. K., 193
Ghosh, S., 40, 230
Giacomelli, G., 13
Giannellini, V., 5
Gibbs, C. G., 93
Gibson, T., 47
Gibson, T. W., 312
Giddings, R. M., 52
Giebfried, J., 28
Gielen, J. E., 328
Gielen, J. W. J., 310
Giersch, W., 23, 38, 51, 179,
231, 238
Giglio, E., 272, 278
Giguere, R. J., 40
Gilad, S., 285
Gilbert, B., 215
Cilgan, M. W., 323
Gillick, S. G., 13
Gillis, H. R., 111
Gilrnore, C. J., 193
Gilmore, D. A., 257
Ginsburg, G. S., 49
Ginzburg, M. A,, 25
Girard, J. P., 60
Giumanini, A. G., 45
Gleizes, M., 4, 74
Glowka, M. L., 55
Glusenkamp, K.-H., 5, 6, 70
Glushko, L. P., 23
Goad, L. J., 311
Goadscloue, N., 4
Godfrey, J. D., 205
Goewert, R. R., 266
Goh, S. H., 202
Gold, P. M., 76
Goldberg, O., 110
Gollob, L., 73
Gomora, E., 226
Gonzalez, A. G., 80, 146,
158, 192, 195, 199, 225,
226, 230,
Gonzalez, D., 40
Gonzalez, P., 230
Gonzalez Sierra, M., 194
Goodman, M., 188
Goodwin, T. W., 235
Gopalkrishnan, B., 39
Gora, J., 55
Gordon, A. G., 41
Gordon, M. H., 102
Gore, K. G., 55, 56, 57, 64
Gorrichon, L., 101
Gorst-Allman, C. P., 172
Goryaev, M. I., 48, 62, 230
Goswami, A., 32,228
Goswami, S., 227
Goswami, U. C., 263
Got, R., 256
Goto, J., 282, 284
Goto, N., 282
Goto, T., 45
Gott, A. M., jun., 286
Gottlieb, H. E., 192, 276,
277, 292, 327
Gottlieb, 0. R., 192
Gougoutas, J. Z., 293
Gould, R. O., 88
Govind, N. S., 262
Govindan, S. V., 146, 155
Govindjee, R., 247, 260
Grabowich, P. G., 272, 293
Gradmann, W., 146
Graebe, J. E., 199
Graf, W., 221,299,300,301,
304
Graham, M. R., 4
Granat, M., 73
Grande, M., 32
Grandi, R., 61
Grandolini, G., 37, 223
Grant, H. G., 59
Grant, P. K., 188
Gras, J.-L., 108
Gray, G. D., 31 1
Gray, N. A. B., 280
Grayson, D. A., 55
Greaves, A. M., 228
Green, M. B., 64
Green, N. M., 327
Green, S., 8
Greenblatt, G. A., 106
Greenhouse, R., 291
Greenlee, M. L., 206
Greenlee, W. J., 130
Grenz, M., 88, 146,188,189,
196
Greuter, H., 64
Grice, P., 54, 160
Grieco, P. A., 61, 207, 223
Grignon-Dubois, M., 51
Grillasia, Y., 15
Grimm, M. F., 266
Grimminger, W., 219
Grishin, Y. K., 51
Groenendijk, G. W. T., 246
Gros, E. G., 195, 317
Groweiss, A., 200, 234
Grumbach, K., 74
Gschwendtner, W., 289
Guchi, S. E., 187
337
Author Index
Gudova, V. N., 55
Guelz, P. G., 44
Guerra, M., 7
Guest, J. R., 266
Guillerm, D., 82
Guirado, A., 45
Guiso, M., 5, 58, 59, 61
Guittet, E., 17
Gujval, V. K., 58
Gullerm, D., 31
Gumulka, J., 305
Gumulka, M., 325
Gunaherath, G. M. K. B.,
228
Gunatilaka, A. A. L., 227,
228, 230
Gunn, B. P., 34
Gupta, B. D., 259
Gupta, C. D., 187
Gupta, R., 14
Gupta, R. K., 75, 88, 106,
111, 115, 146, 155, 170,
172, 188, 189
Gupta, S. R., 58
Gupta, Y. P., 230
Gurria, G. M., 76
Gurst, J. E., 279
Gurudutt, K. N., 42
Gust, D., 243, 256
Gustafson, D. L., 239
Gut, M., 277
Gutierrez, A., 158
Gutman, A., 46
Gutwillinger, H., 33
Guziec, F. S., 53
Haas, A,, 288, 289
Habib, H. A. A., 195
Habib, M. M., 38, 255
Haces, A., 194
Hachey, D., 28
Hackler, L., 303, 327
Hadorn, M., 240
Haffer, G., 324
Haf-Muller, R., 62
Haginiwa, J., 232
Hahn, W. E., 46
Halim, A. F., 172
Hall, F., 169
Hall, I. H., 146, 174, 234
Hall, L. D., 273
Hall, T.-W., 172
Halls, T. D. J., 192
Halsall, T. G., 140
Hamada, Y., 19
Hamanaka, N., 199
Hamaoka, T., 284
Hamelin, J., 44
Hamer, L. F., 325
Hammerschimdt, F. J., 15
Hammond, M. L., 320
Han, D.-S., 215
Han, Y.-K., 99, 118
Hana, G. W., 47
Handley, J. R., 36
Handrick, G. R., 65, 66
Handy, G. A., 146
Haneda, A., 290
Hangauer, D. G., 179
Hanko, R., 40
Hanna, I., 33, 43, 304
Hansbury, E., 282
Hansen, K. B., 257
Hanson, J. R., 121,140,190,
195, 198, 199,292, 305
Hanson, R. C., 258
Harada, M., 230
Harada, N., 5
Harada, T., 21
Harborne, J. B., 4
Harderstein, R., 12
Harding, R. W., 262
Hardy, M., 234, 321
Harlow, R. L., 40
Harms, K., 66
Haroda, N., 277
Haromy, T. P., 232
Haroon, Y., 266
Harref, A. B., 114
Harris, D., 5
Harris, L., 255
Hart, R. J., 318
Hartley, G. S., 64
Hartshorn, M. P., 15, 194
Haruna, M., 144
Harvey, D. J., 5 , 279
Harwood, L. M., 49, 64
Hasa, T., 199
Hasegawa, I., 189
Hasegawa, S., 54, 221
Hashiba, N., 124
Hashimoto, H., 136
Hashimoto, K., 12, 33, 63
Hashimoto, T., 59
Hashimoto, Y., 226
Haslanger, M. F., 45
Hasler, H., 194
Hassam, S. B., 61
Hatem, J., 5
Hattori, H., 49
Hattori, S., 73, 183
Hausen, B. M., 232
Hauser, A., 81
Havel, M., 314, 325
Havinga, E., 310
Hayano, K., 49, 124, 126
Hayashi, C., 284
Hayashi, K., 8 5 , 200
Hayashi, S., 92,183,187,199
Hay Motherwell, R. S., 301
Hayward, G., 258, 259
Heath, R. R., 38,283
Heathcock, C. H., 177, 253
Heck, R. F., 35
Hecker, E., 200
Hedden, P., 199
Hedges, J. I., 232
Hefendehl, F. W., 73
Heftmann, E., 197, 207, 281,
282
Hegde, S. G., 12, 27, 31, 42
Hegedus, L. S., 11
Heide, L., 266
Heikes, J., 45
Heima, K., 86
Heindze, I., 33
Heinvali, M., 15
Heissler, D., 113, 114
Helbling, S. M., 61
Helquist, P., 121
Hendry, L. B., 70
Henke, S., 61
Hensens, 0.D., 228
Herak, R. M.; 272
Herbert, R. B., 4
Herlihy, W. C., 258
Hermann, A. O., 278
Hernandez, J. D., 115
Hernandez, M. G., 195,199,
230
Hernandez, R., 225, 308
Herold, T., 8
Herout, V., 4
Herz, W., 146, 155, 156, 172,
174
Herzfeld, J., 258
Hertzberg, S., 237
Hesse, M., 58
Hethelyi, E., 54
Heuberger, C., 301
Heywood, V. H., 4
Hibino, S., 12
Hickey, J. P., 275, 276
Hieda, T., 263
Hielsen, B. J., 60
Higo, M., 54
Hikino, H., 213
Hilgenberg, W., 210,261
Hill, A., 291
Hillenbrand, G. F., 161
Hilscher, J.-C., 29 1
Hiltunen, R., 5
Hirano, H., 66
Hirano, Y.,72, 269, 290
Hiraoka, K., 237
Hirata, T., 69, 72
Hiroi, K., 61
Hirose, Y., 54, 105, 158, 184
Hirotsu, K., 201
Hirschy, L. M., 41
Hirsl-Starcevic, S., 42
Hiscocks, P. G., 282
Hitchcock, P. B., 199
Hiyama, T., 10, 37, 42
Hixson, S. S., 53
Ho, T. L., 33, 64, 89
Ho, Z. Z., 258
Hoad, G. V., 198
Hoard, L. G., 270
Hobbs, P. D., 247,250
Hochlowski, J. E., 75, 202
Author Index
338
Hocquemiller, R., 85
Hoehne, E., 198, 272, 273
Hoeneisen, M., 146
Hoffmann, H. M. R., 40,47
Hoffmann, J. J., 60, 219
Hoffmann, K., 286
Hoffmann, R. V., 12
Hoffmann, R. W., 8
Hofmeister, H., 323
Hogge, L., 73
Hohn, J., 11
Holker, J. S. E., 87
Holland, D., 64
Holland, H. L., 329
Holly, S., 278
Holub, M., 174
Honda, K., 89
Honda, T., 223
Honig, B., 258,259,260
Honkan, V. A., 202
Hooper, C. L., 71
Hopf, H., 260
Hoppe, D., 40
Hoppen, V., 289
Horgan, R., 238
Hori, M., 210
Hori, T., 50
Horiai, H., 200
Horibe, I., 170
Horinaka, A., 35
Horiuchi, C. A.,295,360,318
Horn, P., 213
Horsewood, P., 294
Horunka, A., 37
Horvath, G., 328
Hosakawa, H., 52
Hoshino, Y . , 13
Hoskins, L. C., 257
Hosoda, H., 283
Hosomi, A., 16
Hostettmann, K., 7,234,283
Hostettmann-Kaldas, M., 7
Howard, B. M., 188
Howard, D. L., 231
Howbert, J. J., 103
Howden, M. E. H., 200, 318
Howell, S. C., 81
Hoye, T. R., 81
Hsieh, C.-L., 258
Huang, H.-C., 146
Huang, J. T., 58
Huang, K.-S., 260
Hubbard, L. M., 259
Nuber, C . P., 228
Huber, U., 47
Hubscher, J., 269, 318
Huchette, D., 33
Hudlicky, T., 63, 135
Huffman, J. C., 39, 223
Huffman, J. W., 156, 161
Hull, W. E., 276
Huls, R., 226
Huneck, S., 230
Hung, H. K., 31
Hunt, J. M., 73
Hunter, G . L. K., 57
Hunter, I. R., 281, 282
Hurst, K. M., 130
Hurtado, H. E., 204
Husain, J., 271
Husain, M., 290
Hutchinson, C. R., 60, 61
Hutchinson, S. A., 85
Hutson, K. G., 266
Hwang, K.-J., 38
Hylands, P. J., 228
Iacobucci, L. A., 36
Iavarone, C., 5, 58, 59, 61
Ibe, K., 74
Ibragimova, N. D., 55, 56
Ibuka, T., 146
Ichikawa, Y . , 158
Ichimoto, I., 33
Ichimura, K., 74
Ichinohe, Y . , 232
Ichinose, I., 20, 79, 203
Ida, T., 312
Ifeodike, N. P., 216
Ignatov, V. N., 271
Iguchi, K., 29, 60, 200
Iguchi, M., 14, 252
Ihm, H., 54
Ihn, W., 230, 279
Iida, H., 195
Iida, T., 174, 274, 277
Iijima, S., 44
Iino, M., 130
Iitaka, Y., 32, 59, 195, 215,
226, 232, 269,
Ikan, R., 74
Ikawa, I., 22
Ikeda, R., 199
Ikegami, A., 256, 260
Ikegami, S., 136
Ikegawa, S., 284
Ikekawa, N., 269, 290, 291,
314, 316
Ikenoya, S., 266

Ikram, M., 234
Imagawa, D. K., 38
Imagawa, T., 60, 61
Imai, S., 194, 204
Imai, T., 199
Imakura, Y., 58, 174
Imamura, P. M., 194
Imre, S., 80
h a , K., 14, 252
Inamoto, T., 210
Inanaga, J., 241, 243
Inari, S., 277
Inokuchi, T., 160
Inomata, K., 22
Inoue, H., 183
Inoue, K., 13, 61, 70
Inoue, S., 76, 89, 264
Inoue, T., 214, 216
Inouye, H., 57, 59, 61, 70

Inouye, J., 4
Inui, H., 234
Inui, S., 52
Invergo, B. J., 25, 64
Ionov, S. P., 271
Ionora, E. I., 33
Ireland, R. E., 205
Irie, H., 36
Irismeto,v M. P., 230
Isae, S., 60
Tsaera, Z. G., 43, 5 5 , 56, 57
Isakov, V. V., 216
Ise, F., 20, 203
Ishi, K., 203
Ishida, T., 73
Ishiguro, M., 265, 290, 291,
314, 316
Ishihara, M., 59
Ishihara, S., 284
Ishii, H., 234
Ishii, K., 26, 79, 255
Ishikawa, H., 18, 25
Ishikawa, K., 12, 16, 259
Ishikawa, T., 274
Ishiwatari, M., 245
Ishiwari, H., 60
Ishizone, H., 226
Islamov, R., 188
Islimyeli, S., 80
Ismail, J., 47
Isobe, T., 196, 197
Itai, A., 226, 269
Ito, I., 46, 72
Ito, K., 144, 174
Ito, M., 43, 189
Ito, S., 13, 28, 142, 143, 146,
190
Itoh, A., 29, 37, 42, 63

Itoh, T., 213, 214
Itoi, K., 62
Itoigawa, M., 174
Itokawa, H., 187
Ives, J. L., 294
Iwabuchi, H., 130
Iwabuchi, J., 5, 277
Iwadare, T., 116
Iwai, M., 14, 72
Iwamoto, M., 33, 51
Iwamura, H., 32
Iwasa, T., 260
Iwasawa, N., 31, 86, 253
Iwashita, T., 184
Iwata, C., 165
Iwata, I., 34, 50
Iwata, M., 232
Iyengar, R., 52, 70, 88
Iyer, R. I., 256
Izawa, K., 216
Izac, R. R., 92, 183
Izotova, L. V., 55
Jackson, W., 254
339
Author Index
Jackson, W. K., 295, 318
Jacobi, P. A., 170
Jacobs, H., 5 5
Jacobs, H. J. C., 310
Jacoli, G. G., 228
Jacquemin, H., 59, 156
Jacques, J., 325
Jacques, R., 74
Jacquier, R., 114
Jadhav, P. K., 115
Jaffer, J. A., 279
Jagodzinski, J. J., 305
Jahodar, L., 58
Jain, G. K., 231
Jain, K. M., 258
Jakobsen, P., 46
Jakupovic, J., 66, 75, 111,
116, 117, 146, 155, 158,
169, 170, 174, 187, 188,
189, 196
Jallali-Naini, M., 82
Jalsovszky, G., 278
James, J. C., 219
Janero, D. R., 255
Janiszo wska , W., 234
Janitschke, L., 48
Jansen, P. A. A., 246
Janssen, B., 298
Janus, J., 50
Jarchow, 0. H., 232
Jarvis, B. B., 93
Jasiczak, J., 321
Jautelat, M., 61
Jefferies, P. R., 15, 78, 186,
188, 189, 202
Jeffery, C., 111
Jeffrey, S. W., 255
Jeger, O., 209, 255
Jelenkovic, B., 272
Jennings, B. H., 308
Jensen, N.-H., 257, 259
Jensen, S. R., 57, 58, 59, 60,
70
Jensen, U., 21
Jerebzoff, S., 261
Jerebzoff-Quintin, S., 261
Jerris, P. J., 119
Jewers, K., 279
Jigajinni, V. B., 298
Jimenez, F. G., 226
Jizba, J., 169
Joffe, A. Z., 213
Johansson, L. B. A., 258
John, L. S., 321
Johne, S., 58
Johnson, D. F., 289, 298
Johnson, K. K., 13
Johnson, M., 72
Johnson, M. A., 5,205
Johnson, M. W., 299
Johnston, J. O., 324
Jolad, S. D., 60, 219
Jommi, G., 184, 194
Jones, A. J., 15
Jones, B. B., 36
Jones, D., 266
Jones, G., 282
Jones, T. H., 60
Jones, W. A., 271
Jonkers, F. L., 34
Jordan, J. R., 283
Joseph, J. M., 312
Joseph-Nathan, P., 103, 115
Joshi, B. C., 4
Joshi, B. S., 227
Joshi, G. D., 5 5 , 56, 64
Joshi, K. C., 192
Joshi, R. S., 56
Jost, P. C., 285
Joucla, M., 44
Joulain, D., 31
Julia, M., 16, 39, 49, 62, 64,
89, 239
Julia, S., 17, 64
Julien, R., 272
Jung, M. E., 181
Jungk, S., 69
Junior, P., 59
Juranic I., 288
Kabore, I., 42
Kabuto, C., 81, 143, 213
Kad, G. L., 21
Kadam, S. R., 296
Kadota, S., 213
Kaegi, H., 246
Kagan, H. B., 4
Kahn, M., 135
Kaiya, T., 199
Kaji, K., 12, 20, 33, 63
Kajihara, Y., 12, 16
Kajtar-Peredy, M., 256
Kakitani, H., 251, 259
Kakitani, T., 251, 259
Kalikhman, I. D., 46
Kalinovskii, A. I., 230
Kalisky, O., 260
Kalkoff, H., 50
Kalvoda, J., 272, 289
Kalyani, K., 193
Kamber, M., 243
Kameoka, H., 70
Kametani, T., 27, 28, 29, 34,
80,223, 252, 314
Kamernitskii, A. V., 271,272
Kamga, C. S., 221
Kamigauchi, T., 189,234
Kamikawa, T., 196
Kamogawa, H., 259
Kanaiwa, T., 115
Kanakura, A., 10
Kanaoka, M., 230
Kane, B. J., 14, 41, 45, 50
Kaneko, H., 85, 238, 252,
253
Kanemoto, Y., 124
Kano, S., 12
Kano, M., 184

Kantor, E. A., 16
Kao, J. P. Y., 78
Kao, L. C., 35
Kapadia, G. J., 60
Kapil, R. S., 228
Kapundu, M., 226
Karaseva, A. N., 56, 57
Karavaeva, K. A,, 256
Karim, A., 174
Karimian, K., 69
Karle, J., 270
Karlin, V. V., 56
Karp, F., 70, 71
Karpf, M., 118
Karpuj, L., 271
Karras, M., 28
Kartasheva, Z. S., 245
Kartashov, V. R., 46
Kartonozhkina, 0. I., 25
Kasahara, C., 206
Kasahara, K., 11
Kasai, R., 234
Kasaikina, 0. T., 245
Kasal, A,, 279, 294, 324
Kashin, A. N., 49, 51
Kashiwada, Y., 203
Kashman, Y.,200, 234
Kasprzyk, Z., 234
Kassner, H., 160
Katagiri, T., 30, 251
Katai, M., 231
Katakawa, J., 36
Katayama, C., 99, 157
Katayama, K., 266
Katayama, T., 256
Kating, H., 66
Kato, F., 262
Kato, H., 230
Kato, K., 29, 79, 163, 238,
252,253, 262, 306
Kato, M., 86
Kato, T., 20, 79, 141, 199,
203, 253
Katsui, G., 266
Katsui, N., 163
Katsuki, T., 23, 27, 241, 243
Katsuyama, K., 243
Katzenellenbogen, J. A., 17
Kavara, T., 9
Kaverin, V. V., 50
Kawada, M., 19,251
Kawaguchi, A., 4
Kawaguchi, T., 62
Kawai, H., 264
Kawakami, S., 64
Kawamoto, A. H., 258
Kawamura, N., 283
Kawanisi, M., 60, 61
Kawano, Y., 64
Kawara, T., 39
Kawasaki, T., 214
Kawashima, H., 194
Kawashima, K., 33
340
Kawashima, T., 190
Kawazu, K., 176
Kayukova, G. P., 286
Kazi, M. A., 58
Kazlauskas, R., 200
Keana, J. F. W., 285
Keiderling, T. A., 6
Keim, W., 12
Kelecom, A., 275
Keller, P., 323
Keller, U., 32
Kemertelidze, E. P., 73
Kemmerling, M., 266
Kempe, U. J., 172
Kenne, L., 234
Kepner, R. E., 73
Kerb, U., 308, 323
Kergomard, A., 299, 329
Kern, M., 48
Kerr, K., 66
Kessel, C. R., 185
Khan, I. A., 307
Khan, N. H., 290
Khan, S. A., 223
Khan, V. A., 73
Khanna, N. M., 46, 231
Khanna, R. N., 67
Khanra, A. S., 57
Khatri, L. M., 58
Khastgir, H. N., 228
Khoi, N., 223
Kholi, J. C., 14
Khorana, H. G., 260
Khuong-Huu, Q., 42
Khrostik, G. M., 48
Kido, F., 81, 165
Kido, M., 158, 203, 210
Kienzle, F., 240
Kikuchi, H., 88, 99, 157, 200
Kikuchi, M., 15
Kikuchi, T., 213, 230
Kikuchi, Y . , 214
Killinger, T. A., 61
Kim, H.-O., 230
Kim, J. B., 285
Kim, S.-W., 179
Kimbu, S. F., 221
Kimmel, Y., 66
Kimura, K., 34
Kimura, M., 273
Kimura, O., 214
Kirnura, Y., 21, 234, 260
King, A. O., 18
King, R. M., 62, 66, 73, 75,
88, 106, 114, 115, 116, 117,
146, 155, 156, 158, 169,
170, 172, 174, 186, 187,
188, 189, 195, 196, 225
Kinghorn, A. D., 85
Kingsley, P. B., 266
Kini, A,, 246
Kinoshita, M., 135
Kinosita, K., 260
Kinting, A., 42
Author Index
Kirby, G. W., 294
Kircher, H. W., 225
Kirfel, A., 181
Kirk, D. N., 140, 273, 303,
322, 323
Kirkwood, P. S., 197, 198
Kirmse, W., 53
Kirson, I., 277, 292
Kirtany, J. K., 67, 103
Kisaki, T., 31, 263, 264
Kise, N., 64
Kiselev, A. V., 282
Kisiel, Z., 6
Kitagawa, I., 31, 46, 48, 189,
210,234
Kitahara, H., 165
Kitahara, T., 15
Kitazawa, E., 187
Kitchin, J. P., 35
Kitson, D. H., 85
Kim, H., 234
Kizuka, K., 3 11
Kjonaas, R., 71
Klaui, H., 235
Kleijn, H., 19, 78
Klein, E., 33
Klein, P. D., 280
Kleinig, H., 260
Klemmenson, P. D., 64
Klimash, J. W., 146
Klimetzet, D., 28
Klina, W. L., 18
Klinotova, E., 231
Klyner, Y. P., 41
Kneen, G., 64
Knight, D. W., 21, 75, 76
Knight, J. C., 328
Knights, S. G., 305
Knipser, W., 14
Knoblauch, K., 54
Knoll, H. E., 266
Knoll, F. M., 22
KO, S. S., 130
Kobayashi, K., 57
Kobayashi, M., 77,200,210,
229, 253
Kobayashi, S., 58
Kobayashi, Y., 234, 284
Koch, H., 47
Koch, M., 58, 59
Kochetkov, N. K., 264
Kochhar, K. S., 36
Kocienski, P. J., 24
Koco'r, M., 298
Koc'orsky', P., 290, 293, 294,
325
Kodama, H., 238
Kodama, K., 257
Kodama, M., 28, 142, 143,
146
Koden, M., 287
Koedam, A., 44
Koenst, W. M. B., 252
KGster, F.-H., 111
Koga, T., 289

Kogami, K., 85
Kohda, A., 36
Kohda, H., 196
Kohen, F., 285
Kohout, L., 280, 318
Koike, K., 193
Koizumi, N., 314
Kojo, K., 33, 51
Kokuryo, M., 273
Kolhe, J. N., 296
Kolind-Andersen, H., 64
Kott, J. R., 47
Komatsu, S., 282
Komel, R., 327
Kominami, G., 284
Kon, K., 60
Kondo, H., 253
Konno, C., 213
Kono, M., 284
Konopelski, J. P., 51, 52
Konoshima, T., 234
Konuspaev, S. R., 25
Koolman, J., 286
Koolstra, R. B., 310
Koppel, C., 74
Korableva, N. P., 256
Korenstein, R., 260
Korobkova, 0. I., 46
Kortmann, D., 289
Koshimizu, K., 32, 73
Kosugi, H., 63
Koszyk, F. J., 135
Kotake, H., 22
Kotsuji, K., 61
Kouno, I., 130
Kouyama, T., 260
Kowalski, C. J., 40, 45
Kowata, N., 111
Koyama, K., 15,234
Koyama, T., 77
Koyama, Y., 262
Kozlov, E. I., 251
Kozlov, N. G., 45
Kozlowska, M., 57
Kozlowskagramsz, E., 46
Kozlowski, J. F., 146
Kozuka, M., 146
Kraus, G. A., 98
Kraus, W., 218, 219, 222
Krause, H. W., 42
Kramer, S. J., 77
Kramp, W., 169, 172
Kreiser, W., 33, 48
Kremers, P., 328
Kreutz, W., 260
Kreuz, K., 261
Krishendhar, A., 66
Krishna Rao, G. S., 67
Krishnasamy, V., 56
Kritskaya, I. I., 6, 48
Kritsky, M. S., 262
Krochmal, E., 72
Kropf, A., 259
Author Index
Kroszczynski, W., 298
Krow, G. R., 46
Krueger, H., 284
Kruglaya, 0.A,, 46
Kruppa, G., 46
Krgukov, P. G., 260
Krywuta, S., 238
Ksander, G. M., 205
Kubo, I., 196
Kubo, S., 163
Kubota, N., 183
Kubota, T., 196, 197
Kucaba, W., 59
Kuchin, A. V., 12, 48
Kuczynski, H., 43
Kudryavtseva, M. I., 37
Kueh, J. S. H., 136
Kula, J., 38
Kulesha, I. D., 318
Kulikova, K. E., 272
Kulishov, V. I., 272
Kulkarni, G. H., 55, 56, 57,
64
Kulshreshtha, M. J., 46
Kumagai, A., 230
Kumagai, T., 20, 79, 203
Kumagi, M., 11
Kumar, N., 146, 156, 172,
174
Kumar, S., 4
Kumar, V. P. S., 226
Kumobayashi, H., 42
Kunesch, N., 85
Kurane, R., 74
Kurata, K., 99
Kurata, T., 51, 67
Kurek, A,, 325
Kurihara, T., 15
Kurita, N., 74
Kuriyama, K., 170
Kurobe, H., 28, 29, 34, 80,
252
Kurosawa, E., 88, 111, 157
Kurusu, Y., 13
Kusabayashi, S., 287
Kushinsky, S., 282
KUSS,E., 283
Kusumoto, S., 200
Kutchan, T. M., 63, 135
Kutney, J. P., 54, 55, 160,
210,228
Kutnik, J., 259
Kutschabsky, L., 198
Kuwajima, I., 46
Kuwata, M., 41
Kuzmichkin, P. V., 62
Kuznetsova, R. E., 25
Kwon, Y. C., 312
Kyogoku, Y., 210
Kyonaas, R., 72
Laats, K., 15
Lablache-Combier, A., 172
341
Labler, L., 290
Lachenmeier, A,, 240
Ladika, M., 76
Ladner, W., 8
Ladwa, P. H., 55
Lafont, R., 282
Lafontaine, J., 166
Laguerre, M., 51
Lahav, M., 271, 309
Lakshminarayana, V., 214
Lal, M., 37
Lalande, J., 31
Lallemand, J.-Y., 31,82, 174
Lamatkin, A. I., 41
Lamazouene, A. M., 52
Lamb, N., 48
Lambert, G., 65
Lamberton J. A,, 190
Lambotte, R., 328
Lammel, G., 60
Lamparsky, D., 32
Land, E. J., 243
Lander, N., 51, 66
Lang, C., 303
Lange, G. L., 42, 142
Lansbury, P. T., 179
Lanteri, S., 43
Lantzsch, R., 61
Lanzetta, R., 211
Lapalme, R., 45
Larcheveque, M., 82
Lardicci, L., 13
Laszlo, P., 328
Laszlo, T., 245
Laudova, V., 169
Lauer, M., 44
Lauher, J. W., 202
Laurent, H., 323
Lautens, M., 142
Law, J. H., 77
Lawrence, R. F., 10
Laycock, D. E., 302
Lazare, S., 33, 50, 304
Lazarev, Y. A., 260
Le, A. T., 76
Leander, K., 66
Leblanc, R. M., 259
Leboeuf, M., 85
Leclaire, R., 255
Leclercq, J. M., 259
Leclercq, M., 255
Lee, E., 315
Lee, G. J.-L., 282
Lee, J. G., 50
Lee,K. H., 53, 146, 174, 223,
234
Lee, T. S., 238
Lee, Y.-W., 315
Legon, A. C., 6
Lehmann, D., 59
Leiserowitz, L., 271, 309
Leistner, E., 266
Lemaitre, P., 3 1, 82
Le Merrer, Y., 89
Lemley, A. T., 258

Lemoine, G., 286
Lenton, J. R., 197
Lepicard, G., 272
Leppik, R. A,, 328
LeQuesne, D. W., 196
Leresche, J. P., 28
Leroy, E., 33
Leroy, F., 271, 272
Lesage, M., 47
Lester, D. J., 35, 213, 296,
299
Lethuillier, G., 62
Letoublon, R., 256
Leu, J. L., 196
Leuenberger, F. J., 237
Leutwiler, L. S., 261
Levina, I. S., 271, 272
Levine, S. G., 39
Levisalles, J., 298
Levy, S., 66
Lewicka-Piekut, S., 321
Lewis, A., 258
Lewis, K. G., 228
Lewis, N. J., 45
Ley, S. V., 81, 82, 83, 213,
295,299
Li, H., 312
Li, L. N., 312
Liaaen-Jensen, S., 237, 238,
243
Liang-Liu, W., 35
Lichtenberg, F., 40
Lichtenthaler, H. K., 265
Liefertova, I., 58
Lightner, D. A., 5, 33
Lin, J. T., 197, 281
Lin, S. H., 258
Lin, T., 225
Lin, Y. Y., 280
Lin, Z.-W., 197
Lincoln, D. E., 73
Lindblom, G., 258
Ljndig, C.,326
Lmdley, M. R., 320
Lindley, P. F., 271
Lindner, H. R., 285
Lipnicka, U., 50
Lisa, M.; 58
Lischewski, M., 198
Litaka, Y., 192
Litchfield, C., 237
Little, R. D., 135, 139
Little, R. J., 275
Lituyakova, E. N., 25
Litvin, F. F., 259, 260
Liu, C., 17
Liu, H. J., 31, 46, 114
Liu, R. S. H., 246, 250
Lloyd, H. A., 60
Lobanova, T. V., 245
Lochynski, S., 56
Loliger, P., 247
Lofgren, C. S., 77
342
Logan, R. T., 297, 299
Lohmann, J. J., 64
Lohr, K., 142
Lojewska, Z., 259
Lok Ho, T., 39
Lolmlund, C. E., 93
Lombardo, L., 199, 205
Lombardo, L. R., 266
Lonergan, G. C., 164
Lonergan, G. T., 39
Loomis, W. D., 4, 72
Lopez-Diaz, I., 262
Lopez, H., 114
Lorenc, L., 272,273,288,289
Lotan, D., 250
Lotan, R., 250
LOW,C.-E., 280
Lu, P. Y., 259
Luche, J. L., 13
Luckner, M., 4
Luft, R., 41
Lugaro, G., 210
Lugtenburg, J., 246,258,259
Lukacs, G., 4, 181, 276
Lukashin, A. V., 257
Lusinchi, X., 303
Luteijn. J. M., 65, 204
Lutz, W., 36
Lyman, H., 239
Lynch, J. E., 44
Lyon, G. D., 54
Lyse-Petersen, S. E., 59
Lythgoe, B., 318
Lyuts, A. E., 48, 62
Mabry, T. J., 193
MacAlpine, D. K., 123
Macaulay, J. B., 40
McCaskill, R. H., 131, 134
McCombs, C. A., 181
McConnell, 0. J., 31, 79,201
McCorkindale, N. J., 85, 86
McCormick, J. P., 299
Macdonald, J. E., 10
McDonard, J. T., 6
McElhinney, R. S., 50
McGarry, G., 299
McGrath, M. J., 55
McGuire, F. J., 116
McInnes, A. G., 277
McIntyre, C. R., 86, 234
McIntyre, D. E., 78
McIntyre, H. B., 281
Mackae, I. C., 38
McKervey, M. A., 174
MacKinnon, S., 5
MacKoul, P. J., 327
MacMillan, J., 197, 198
McMillen, D. A., 285
McMorris, T. C., 323
McMurry, J. E., 205, 300
McMurry, T. B. H., 160
McPhail, A. T., 190
Author Index
Maddocks., P. J., 10
Madruzza, G. F., 194
Maeda, K, 286
Maeda, N., 306, 3 11
Maemoto, K., 36
Maentele, W., 260
Magasuna, K., 16
Magno, S., 201
Magnus, P., 20
Magnus, P. D., 52
Mahato, S. B., 189, 230
Mahmoud, I. I., 85
Mahmoud, M. M., 271
Mahmoud, Z. F., 102
Mahon, M., 81, 82, 83
Mailahn, W., 107
Maillo, M. A., 83
Main, P., 272
Maione, A. M., 270, 306
Maiti, S. N., 230
Maitra, M., 234
Majerski, Z., 42
Majewski, M., 17, 63
Maji, K. S., 204
Makhankov, V. V., 216
Makin, H. L. J., 282
Makino, M., 259
Makowski, B., 46
Malakov, P., 190
Maldonado, L. A., 15
Malingre, T. M., 60
Malinovskaya, G. V., 216
Malinovskii, M. S., 23
Mallavarapu, G. R., 226
Malleron, J. L., 11, 43
Mallik, B., 258
Mallinson, P. R., 271
Malone, J. F., 174
Maltsev, D., 264
Manchand, P. S., 200, 202
Mancuso, A. J., 288
Mandai, T., 19, 251
Mander, L. N. 195, 199, 205
Mandloi, D., 234
Mane, B. M., 56, 57
Mangoni, L., 211
Manh, D. D. K., 100
Manitto, P., 207
Manley, R. P., 314
Mann, V., 283
Mannschreck, A., 7
Mansilla, H., 158
Mansour, E . 4 . S., 228
Mantulin, W. W., 286
Manukov, E. M., 62
Mao, B., 247,259, 260
Maoka, T., 237
Maradufu, A., 146
Marazza, F., 121
Marcelin, G., 50
Marcelle, G. B., 221
March, G., 201
Marchand, B., 46
Marekov, N. L., 312
Marini Bettolo, G. B., 278

Marini-Bettolo, R., 325
Markowicz, S. W., 51, 52
Marples, B. A., 306
Marquez, C., 191
Marsaidi, A. J., 194
Marschall, H., 11
Marshall, D. G., 202
Martin, A., 194
Martin, B. R., 66
Martin, J. D., 80
Martin, P., 64
Martin, V. S., 27
Martha, D., 63
Martinez-Ripoll, M., 190,
192
Martinkus, C., 72
Martinkus-Taylor, C., 72
Martino, J. P., 312
Marunaka, T., 197
Maruyama, T., 81
Marx, P., 5, 6
Masaki, Y., 12,20,33,63
Masamune, T., 29, 79, 99,
163, 166, 309, 311
Mascarenhas, I. P., 190
Mash, E. A., 76
Mashiko, T., 172
Mashima, K., 16
Mason, A. N., 328
Mason, K. G., 306
Masood, M., 234
Massey, I. J., 280
Massiah, T. F., 271
Massy-Westropp, R. A., 75
Mastalerz, H., 291, 304
Masuda, H., 59
Masuda, K., 38,225
Masuda, S., 21
Masuyama, Y., 13
Matawowski, A,, 14
Materna, J., 194
Mathew, K. K., 18
Mathew, P. C., 41
Mathews, R. S., 61
Mathies, R., 258
Matsubara, Y., 24,35,41,42,
50, 51, 53
Matsuda, R., 73, 183, 184
Matsui, M., 15
Matsui, T., 98
Matsuki, Y., 28
Matsumato, M., 13
Matsumoto, H., 246
Matsumoto, T., 49, 99, 115,
123, 124, 126, 134, 136,
194, 199, 204, 213, 214,
274, 277
Matsumura, C., 60
Matsumura, K., 327
Matsumura, Y., 86
Matsunaga, T., 264
Matsunami, S., 24
Matsuno, T., 237, 262, 263
343
Author Index
Matsuo, A., 92, 183, 187
Matsuo, K., 116
Matsuo, N., 64
Matsuo, T., 19
Matsushita, H., 23, 85, 253
Matsushita, K., 234
Matsuura, Y., 199
Matsuzaki, T., 199
Matteson, D. S., 50
Matveets, Y. A., 260
Matz, J. R., 39
Maumy, M., 49
Maurer, B., 81
May, E. L., 66
Mayer, G. D., 327
Mayer, H., 237, 240, 247,
253
Maynard, J. K. L., 41
Mayol, L., 201
Mazumdar, P. C., 189
Mazumder, A., 52
Mazur, Y., 276, 309
Mazza, F., 270, 272, 306
Mazzola, E. P., 93
Meadows, J. D., 314
Mechoulam, R., 51, 66, 74,
318
Medarde, M., 48, 118
Mednikova, N. A., 251
Medwick, T., 282
Meganathan, R., 266
Megges, R., 272,273
Meguri, H., 199,231
Mehrotra, A. K., 52
Mehta, G., 39, 135, 193
Meiboom, S., 287
Meier, B., 59
Meier, H., 193
Meier, W., 290
Meijer, E. W., 53
Meijer, J., 19
Mekeev, E. M., 255
Mellerio, G., 135
Mellor, M., 136
Meltzer, P. C., 65, 66
Menarchy, M. D., 196
Merchant, J. R., 21
Merchlinsky, M. J., 298
Merienne, C., 222
Merrien, A., 216
Mervic, M., 327
Meskens, F. A. J., 297
Messerschmidt, A., 272, 273
Mesta, C. K., 102
Mestres, R., 37, 40
Metcalf, B. W., 226, 324
Metge, C., 42
Meunier, B., 48, 216
Meyer, M. D., 314
Meyers, A. I., 44
Mhehe, G. L., 31
Michon, J., 53
Micovic, I., 272
Midgley, J. M., 47
Midland, M. M., 8, 312

Mielczarek, I., 63
Mihaashi, S., 187
Mihailovic, M. Lj., 272,273,
288,289
Mikami, Y., 31, 263, 264
Mikkelsen, C. B., 58, 60
Milkova, T. S., 312
Miller, B. W., 273, 322, 323
Miller, D., 246
Miller, J. A., 98
Miller, J. G., 37
Miller, R. B., 160
Miller, R. J., 73
Milner, D. J., 64
Mimura, T., 9, 21
Minachev, K. M., 33
Minale, L., 3, 318
Minami, Y., 134, 197
Minkiewicz, J. V., 35
Minocha, P. K., 234
Minowa, N., 264
Minton, M. A., 61
Mirek, J., 39
Mirza, N. A., 62
Miski, M., 193
Misra, A. N., 41
Misra, L. N., 55, 56
Misra, R. N., 108
Misra, T. N., 258
Misumi, S., 124, 126
Mitchell, S. J., 172, 182, 200
Mitra, A. K., 187, 230
Mitra, R. B., 57, 64
Mitscher, L. A., 19, 293
Mitsuhashi, H., 200
Mitsuki, M., 194
Mitsunobo, O., 289
Mitzka-Schnabel, U., 261
Miura, H., 61
Miura, I., 104, 201
Miura, T., 273
Miyahara, K., 214
Miyahara, Y., 214
Miyai, K., 284
Miyaji, M., 74
Miyamoto, T., 64
Miyamoto, O., 89
Miyanke, T., 18
Miyano, M., 321
Miyashita, M., 52
Miyata, N., 3 11
Miyawaki, H., 38, 50
Miyazaki, S., 38
Mizuno, A., 19
Mizuno, Y., 36
Mkandawire, G. J., 271
Mlotkiewicz, J. A., 124
Mnatsakanyan, V. A., 230
Mpango, G. B., 17, 63
Modi, V. V., 262
Modsen, H. B., 64
Moir, D., 228
Moiseenkov, A. M., 16
Molls, U., 38, 43

Molnar, P.,256
Mondon, A., 183
Monbger, R., 260
Moneti, G., 5
Money, T., 45, 48
Mongrain, M., 166
Monji, N., 284
Monroe, B. M., 36
Montanari, S., 184
Moore, A. L., 243, 256
Moore, P. H., 281
Moore, T. A., 243, 256, 258
Moore, W. S., 73
Mootoo, B. S., 221
Morah, F. N., 60
Morand, P., 291, 304
Morch, L., 8
Moreau, J. L., 14
Moreau, S., 172
Moreno, D. S., 63
Moreno, M., 234
Morera, E., 323
Moretti, I., 5
Morgans, D. J., 20
Mori, K., 19, 21, 38, 62, 63,
77
Mori, O., 35
Moriarty, R. M., 320, 321
Morin, L., 5
Morinaka, H., 68
Morisaki, M., 316
Morita, M., 187
Morita, K., 60
Moriyama, Y., 226
Mornon, J. P., 272, 303
Moroe, M., 54
Morris, D. J., 281
Morris, D. S., 319
Morris, G. A., 275
Morrison, J. C., 254
Morrison, G. A., 299
Morton, R. S., 36
Mortreux, A., 33
Moss, G. P., 241
Moss, R. A., 157
Motherwell, R. S. H., 37
Motherwell, W. B., 35, 37,
292, 296, 307, 321
Motto, M. G., 247
Mourino, A., 320, 321
Mousdale, D. M. A., 255
Mowery, P. C., 260
Mrozinska, P., 37, 43
Muccino, R. R., 18
Muchowski, J. M., 291
Muller, L., 116,146, 169,225
Mueller, R. H., 13
Muller, R. K., 237, 240
Mues, R., 73
Mujano, M., 290
Mukaiyama, T., 21, 31, 86,
283
Mukharnedova, L. A., 37
Author Index
344
Mukherjee, D., 204, 325
Mukherjee, K., 226
Mukherjee, K. S., 193
Mukhopadhyaya, S. K., 204
Mukitanova, T. R., 49
Mulholland, D. A., 219
Muller, B. L., 23
Muller, G. W., 135
Muller, P. M., 13
Muneyuki, R., 50
Munro, M. H. G., 15, 194
Murae, T., 21 1, 223
Murahashi, S. I., 28, 52
Murai, A., 29, 79, 163, 166
Murai, F., 58, 59, 60
Murai, N., 61
Murakami, T., 195
Muraki, S., 32, 141
Muramatsu, T., 57
Murata, S., 124
Murata, Y., 126
Murato, K., 255
Murgia, S. M., 259
Murillo, F. J., 262
Muro-Oka, Y., 22
Murphy, C. J., 53
Murphy, P. T., 15, 201
Murphy, R., 29
Murray, M. J., 73
Murray-Rust, J., 124
Murray-Rust, P., 124
Murthi, G. S. S., 52
Murthy, P. P. N., 98
Murty, V. S., 226
Murty, Y. L. N., 214
Musavirov, R. S., 16
Musiani, M. M., 45
Musser, J. H., 205
Muto, S., 262
Mutsushita, S., 38
Muzart, J., 11, 13
Myers, A. B., 259
Myshenkova, T. N., 40
Myskewnora, T. N., 14
Nabeya, H., 199
Nadaya, K., 183
Naf, F., 21, 179
Nafie, L. A., 5
Nagai, K., 40
Nagai, M., 214, 216
Nagai, S., 46
Nagai, Y., 13
Nagajima, K., 59
Nagakura, A., 54
Nagano, E., 254
Nagao, K., 179
Nagao, Y., 186
Nagaoka, M., 325
Nagar, P. K., 256
Nagasaki, M., 187
Nagasampagi, B. A., 146,
158, 210,232
Nagata, S., 262, 263
Nagumo, M., 258

Nagumo, S., 216
Nahrstedt, A., 15
Naik, D. G., 225
Naik, V. G., 50, 56
Nair, A. G. R., 32
Naito, T., 85
Nakachi, K., 259
Nakagama, H., 21
Nakagawa, K., 62
Nakagawa, T., 200
Nakahara, M., 286
Nakahara, Y., 98
Nakai, J., 45
Nakai, T., 9, 14, 21, 253
Nakai, Y., 79, 203
Nakajima, K., 59
Nakajima, S., 176
Nakamo, S., 64
Nakamura, A., 16
Nakamura, M., 234
Nakamura, N., 27, 255
Nakane, M., 60
Nakanishi, K., 81, 219, 247,
259, 260
Nakanishi, T., 104
Nakano, T., 83, 194
Nakao, Y., 69
Nakashima, T. T., 275
Nakata, T., 85
Nakatani, M., 219
Nakatsu, T., 190
Nakaya, K., 264
Nakayama, K., 319
Nakayama, M., 40, 92, 183,
187, 199
Nakayama, N., 48
Nakenishi, K., 315
Namamura, A., 12
Namanishi, O., 33
Namba, T., 213
Nambara, T., 282, 283, 284
Namikawa, M., 21 1
Nanasawa, M., 259
Nanayakkara, N. P. D., 227,
230
Naoki, H., 70, 184
Narasaka, K., 31
Narayanan, C. R., 225
Narula, A. S., 210
Naruse, N., 61
Naruta, Y., 265
Naruto, M., 61
Narva, D., 258
Nasini, G., 230
Nasipuri, D., 203
Nasybullina, F. G., 37
Natakani, Y., 33
Natalie, K. J.,
Natarajan, C. P., 42
Nathu, N. K., 203
Natu, A. A., 66
Naya, K., 35, 37
Nayak, U. R., 47
Nazarians, L., 146, 172

NCdelec, L., 321
Neef, G., 324
Negishi, E., 18, 23, 253
Negishi, T., 62
Negron, G., 190
Neidlein, R., 243
Neill, S. J., 238
Nelson, C., 276
Nelson, W. H., 257
Nemoto, H., 27, 28, 29, 34,
80, 252, 314
Neron Desbiens, M., 193
Nes, W. D., 207, 210
Nes, W. R., 312
Nesmeyanov, A. N., 48
Neszmelyi, A., 4, 181
Nice, E. C., 281
Nick, H., 45
Nickon, A., 116
Nicoara, E., 245
Nicol, M., 258
Nicolaou, K. C., 43
Nicotra, F., 210, 328
Nielsen, B. J., 5, 57, 58, 59,
70
Niemeyer, U., 5 , 6
Nigarn, M. C., 32, 55, 56
Niknejad, A., 172
Nikolaev, V. F., 6
Nilsson, K., 228
Nishida, K., 190
Nishida, T., 265
Nishida, Y., 54
Nishihama, Y., 59
Nishikawa, J., 276
Nishikawa, K., 19, 251
Nishimura, H., 34, 61
Nishimura, T., 33, 51
Nishino, C., 5 , 50, 51
Nishino, T., 210
Nishioka, I., 66, 203, 215
Nishizawa, A., 9
Nishizawa, M., 24
Niwa, M., 91, 189, 230
Noam, M., 318
Noda, Y., 81, 197
Node, H., 190, 196
Nogami, Y., 289
Nogasampagi, B. A., 73
Noguchi, M., 253
Nokami, J., 60, 99
NoLara, T., 203, 215
Noma, Y., 73
Nomura, D., 130
Nomura, M., 24, 35, 42, 51
Nordblom, G. D., 283
Nordman, C. E., 270
Norin, T., 106, 172
Norman, A. W., 306, 321
Norris, A. F., 319
Notegen, E.-A., 94
Novikov, V. L., 216
Novotny, L., 169
345
Author Index
Noyori, R., 24, 44, 124
Nozaki, H., 25, 29, 37, 42,
63, 183
Nozaki, K., 15
Nozaki, N., 12
Nozari, H., 10
Nozoe, S., 4
Numazawa, M., 270, 289
325
Nunn, M. J., 98
Nyfeler, R., 121
Obermann, H., 33
Oberti, J. C., 195
Obi, Y.,31, 263, 264
OBrien, E., 87
Ochi, M., 201
Ochiai, M., 186
Oda, N., 46
Odeh, I. M. A., 170
ODowd, M. L., 45
Oesterhelt, D., 259, 260
Offermann, W., 7
Ogasawara, K., 38, 206
Ogawa, K., 192
Ogawa, M., 229
Ogihara, Y., 229, 234
Ogiso, A., 187
Ognyanov, I., 172
Ogunkoya, L., 207
Ogura, H., 160
Ogura, K., 77
Ogura, M., 226
Oguri, K., 66,266
OHare, M. J., 281
Ohashu, K., 39
Ohbao, S., 189
Ohfune, Y., 124
Ohloff,G.,23,37,38,51,81,
91,179,231,238
Ohlsson, A., 66, 73
Ohmizu, H., 64
Ohmori, H., 234
Ohmori, M., 319
Ohnishi, R., 49
Ohno, A., 45
Ohno, K., 61
Ohnuma, T., 141
Ohsawa, T., 290
Ohta, Y., 158
Ohtsuka, T., 124, 126
Oikawa, T., 25
Oishi, T., 8 5 , 193, 194,290
Ojhara, B., 77
Ojima, I., 11
Ojinnaka, C. M., 231
Oka, S., 45
Okabe, H., 214
Okada, S., 210
Okada, Y., 15,234
Okamoto, K. A., 73
Okamura, N., 215
Okamura, S., 14
Okamura, W. H., 250, 306,

320, 321
Okano, M., 40, 89, 223, 234
Okawara, M., 19, 42, 62
Oki, M., 40,89
Okita, H., 69
Okogun, J. I., 221, 231
Okorie, D. A., 231
Okubo, A., 264
Okukado, N., 18
Okumura, S., 72
Okuyama, T., 15,234
Olaniyi, A. A., 227
Olesker, A., 43
OlivC, J. L., 39
Oliver, R. W. A., 287
Olson, R. E., 76, 266
Oniarkulov, T. O., 255
Omura, Y., 62
Ong, C. W., 97
Ongena, R., 61
Onishi, A., 264
Onishi, T., 265
Ono, H., 309
Ono, M., 14, 24
Oontento, M., 25
Opferkuch, H. J., 200
Oppolzer, W., 101, 121
Orchinnikov, Y. A., 247
ORegan, P. J., 59
Oriente, G., 186, 201
Oritani, T., 14, 72, 254
Ors, J. A., 38
Orsini, F., 68, 204
Orszanska, H., 37, 40
Ortar, G., 323
Osawa, E., 115, 126
Osawa, Y., 270,289, 325
Oshima, K., 29, 37, 42, 63
Oshima, Y., 213
Osianu, D., 245
Oskoui, M. T., 228
Osugi, J., 286
Otera, J., 19, 251
Ottolenghi, M., 258, 260
Ourisson, G., 73, 183, 207,
208, 209, 211, 225, 232,
309,407
Overman, L. E., 22
Ozaki, Y., 58
Ozawa, S., 42
Oztunc, A., 80
Paaren, H. E., 319, 320
Pachaly, P., 59
Pachlatko, J. P., 129
Pagnoni, U. M., 61
Pagsberg, P. B., 257, 259
Pai, P. P., 55, 56
Pailer, M., 33
Paine, A. J., 46
Pak, A. M., 25
Pak, N. D., 49
Paknikar, S. K., 62, 67, 102,

103
Pakrashi, S. C., 172, 277
Pal, R., 231
Paldugin, V. A., 187, 200
Pale, P., 13
Palfreymer, M. N., 52
Palings, I., 246, 258, 259
Pallix, J. B., 257
Palma, M. M., 73
Palmer, R. A., 271
Palmskog, G., 255
Palyants, N. Sh., 234
Pamingle, H., 23
Pan, D., 235
Pan, Y.-G.,181
Panasenko, I. S., 251
Panorazi, A,, 42
Pande, A., 258
Pandian, S., 266
Pandit, U. K., 296
Pandy-Szekeres, D., 10
Panosyan, A. G., 230
Papagorgiou, V. P., 44
Papanov, G., 190
Papoula, M. T. B., 35
Paquer, D., 4, 5
Paquette, L. A., 21, 41, 42,
46, 99, 118, 119, 129, 139,
297
Paradisi, M. P., 296
Pardo, R., 40, 42
Parikh, V. D., 293
Parish, E. J., 318
Park, 0. S., 15
Park, R. J., 59
Park, Y. Ja, 272
Parker, W., 124
Parra, A., 199
Parrilli, M., 21 1
Partridge, J. J., 318
Parves, M., 174
Paryzek, Z., 211
Pascard, C., 43,48,156,216,
219, 226
Pascoe, K. O., 200
Pasechnik, G. S., 195
Passacantilli, P., 58, 59, 60,
61
Passet, J., 60
Pasteels, J., 202
Patel, B. A., 35
Patel, D. P. J., 22
Patel, S. K., 34
Paternostro, M., 190, 191
Paterson, I., 19, 299
Pathak, V. P., 67
Patil, D. G., 47
Patni, R., 192
Patra, A., 187, 230
Pattenden, G., 10, 64, 105,
136,138,183
Patterson, G. W., 210,273
Patterson, W., 18
346
Paul, D., 271
Paul, V. J., 31
Pauly, G., 74
Pauptit, R. A., 6
Paupurdin, C., 72
Pavanasasivam, G., 93
Pavel, N. V., 272
Pavia, A. A., 39
Pavlin, M. S., 49
Pavlovic, V., 272, 273, 289
Pawson, B. A., 247
Payan, C., 260
Payne, T. G., 188
Pearce, A., 19
Pearson, A. J., 97
Pecher, J., 228
Pedulli, G. F., 7
Pegg, D. T., 274
Pelister, Y.,39
Pelizzoni, F., 68, 204
Pelliciari, R., 31, 192, 194,
252, 324
Pena, A., 199
Pentegova, V. A., 73
Peppard, T. L., 15
Perales, A., 191, 192
Pereira, V. A., 42
Perez, C., 62, 80
Peries, R., 31
Perkins, M. J., 52
Pernold, W., 47
Perz, R., 40
Pete, J. O., 11, 13
Peters, J. A. M., 307
Petiaud, R., 33
Petit, F., 33, 48
Petrasiunas, G. L. P., 53
Petrov, A. A., 286
Petzdolt, K., 323
Pfander, H., 240, 243
Pfenninger, J., 300, 301
Pham, C. C., 4
Philibert, D., 324
Phillips, F. L., 227
Phillips, L. R., 35, 39
Phillipson, J. D., 223
Phinney, B. O., 198
Piatkowski, K., 35, 37, 43
Piattelli, M., 186, 201
Piau, F., 64
Picard, J. P., 10
Pichet, L., 327
Pickard, J., 106
Pickenhagen, W., 62
Pierce, T. E., 36
Piers, E., 172
Pietrzak, J., 298
Pillai, N. K., 307
Pillot, J.-P., 10, 25, 51, 62
Pinchin, R., 196, 215
Pinder, A. R., 156
Pinnick, H. W., 24, 36, 38
Pinto, A. C., 192, 196, 215
Piozzi, F., 190, 191, 230
Author Index
Pirozhkov, S. D., 14, 40
Pirrung, M. C., 118
Pitha, J., 250
Pitt, C. G., 65, 66
Piwinski, J. J., 178
Pizza, C., 318
Pizzi, P., 328
Pizzo, C. F., 34
Platzer, N., 4
Plimmer, J. R., 63
Plummer, T. L., 180
Poddubnaya, S. S., 14, 40
Podlejski, J., 38
Pokhilo, N. D., 216
Pol, A. V., 50, 56
Polavarapu, P. L., 5
Poldidon, G., 59
Poletti, A., 259
Polishchuk, A. P., 272
Polo, M. C., 37
Polonsky, J., 156, 194, 216,
222,223
Polunin, E. V., 16
Pomilio, A. B., 195
Pons, M., 289
Ponsold, K., 273, 282, 302
Ponton, J., 121
Poots, I., 68
Popa, D. P., 195
Popli, S. P., 228
Popov, A. A., 49
Popov, 0. S., 255
Popov, S., 312
Popovitz-Biro, R., 271, 309
Popp, A., 73
Popplestone, R. J., 23
Porath, G., 66
Porte, A. L., 123
Porter, J. W., 235
Postlewhite, A., 50
Potlier, E., 40
Poulose, A. J., 35, 71
Poulter, C. D., 20, 63, 76
Pouskouleli, G., 275, 276
Pouzar, V., 314, 325
Povelikina, L. N., 46
Povodyreva, I. P., 5 5 , 56
Powell, L. A., 250, 251
Pownall, H. J., 286
Poznyakov, S. P., 250
Pradhan, S. K., 296
Prager, R. H., 29
Prakasa Rao, A. S. C., 93,99
Prange, T., 43,156,226,270,
297
Prasad, R. S., 205
Prasanna, S., 226
Precigoux, G., 271, 272
Prelesnik, B. V., 272
Prestwich, G. D., 74, 202
Pretzsch, G., 174
Pribytkova, I. M., 20, 34
Price, H. C., 277
Price, J. C., 256
Price, L. G., 299

Priester, W., 13
Prokopiou, P. A., 301
Proksch, P., 44
Protiva, J., 231
Proudfoot, G. H., 186
Provost, J., 234
Pugliese, J. C., 254
Purdie, N., 278
Purdy, R. H., 281
Puritskii, K. V., 40
Purkina, A. V., 286
Purushothaman, K. K., 146,
193
Pusil'nikova, S. D., 286
Puzitski, N. V., 14
Queirez, P. P., 192
Quilliam, M. A., 279
Quinn, P. J., 266
Quirk, J. M., 39, 294
Raasch, M. S., 51
Rabanal, R. M., 191
Rabaron, A., 59
Rabenstein, D. L., 275
Rabi, J. A., 296
Radhakrishnan, R., 260
Radhakrishnan, T. V., 296
Radics, L., 256
Radley, M. E., 197
Raffauf, R., 196
Raffelsberger, B., 58
Raghavan, N. V., 251, 259
Rahier, A., 210
Raisanen, S., 5
Rajendran, K., 102
Rakhmankulov, D. L., 16
Ralph, D. E., 104
Ramachandra Rao, V., 53
Ramamurthy, V., 250
Raman, P. S., 18
Raman, T. S., 266
Ramdahl, T., 238, 243
Ramdazzo, G., 69
Ramirez, M. A., 80
Ramise, A., 46
Ranganathan, D., 52
Ranganathan, S., 52
Rangaswami, S., 228
Ranise, A., 43
Rapp, A., 14
Rao, A. S., 38, 67
Rao, B. C., 192
Rao, C. B., 52, 60
Rao, M. N., 226, 230
Rao, R. N., 281
Rassat, A., 53
Rassl, D., 37
Rastogi, R. P., 115, 207, 258
Raston, C. L., 188, 189,202,
226
347
Author Index
Ratner, V. V., 43, 55
Rau, W., 261, 262
Raucher, S., 10, 38
Rautenstrauch, V., 12, 14
Ravelo, A. G., 230
Ravelo, F., 80
Raverty, W. D., 44
Ravi, B. N., 234
Ravichandran, R., 302
Ravindranath, B., 42, 67
Ray, R., 50
Rayer, R. C., 62
Raymaud, J., 280
Razdan, R. K., 65, 66
Read, C. M., 292
Read, R. W., 292, 302
Reck, G., 198, 273
Recti, M. T., 8
Reddy, A. V., 39, 135
Reddy, G. C. S., 228
Reddy, G. S., 300
Reddy, N. S., 106
Redshaw, S. D., 22
Rees, J. C., 6, 54
Reetz, M. T., 92, 297
Reger, D. L., 255
Reh, E., 282
Reich, H. J., 76
Reichert, U., 177
Reiffsteck, A., 281
Reinbold, A. M., 195
Reis, F. A. M., 215
Renstrom, B., 237
Rentzepis, P. M., 259
Repke, K., 326
Rettig, M. F., 64
Reutov, 0. A., 49, 51
Reverdy, G., 53
Revial, G., 101
Rey, M., 110
Reye, C., 40
Ribaldi, M., 192
Riccio, R., 318
Richard, C., 323
Riche, C., 85
Rickards, R. W., 37
Riddell, F. G., 124
Riechst, R. A. K., 38
Rieger, D. L., 38
Riehl, J.-J., 113, 114
Riesselmann, B., 286
Rihs, G., 272, 289
Rilling, H. C., 76
Rimpler, H., 59, 60
Risinger, G. E., 69
Rist, G., 272, 289
Ritter, F. J., 77
Rivera, A., 308
Rivier, L., 197
Rizvi, S. H., 228
Rizvi, S. Q. A., 275
Roberts, J. S., 116, 124
Roberts, M. R., 161
Robinson, C. H., 308
Robinson, H., 62,66,73, 75,

88, 106, 114, 115, 116, 117,
146, 155, 156, 158, 169,
170, 172, 174, 187, 188,
189, 195, 196, 225
Robinson, J. M., 279
Robinson, T., 4
Robinson, W. T., 15, 194
Rodgers, M. A. J., 257, 259
Rodier, N., 272
Rodini, D. J., 9, 21, 40, 48,
63
Rodionov, A. V., 247
Rodriguez, B., 187, 188, 190,
191,192,225
Rodriguez, M., 5
Rodriguez, V. M., 234
Rodriguez-Hahn, L., 190
Roedam, A., 73
Rogers, D., 227
Rogerson, C. V., 47
Rogues, R., 6
Rohmer, M., 207, 208, 209,
232
Rohner, H. C., 53
Rojas, A., 194
Romdn, L. U., 115
Romanov, N. A., 16
Romeo, A., 270, 306
Ronald, R. C., 71
Ronchetti, F., 210, 328
RBnneberg, H., 238
Roobeck, C. F., 33
ROOS,R. W., 282
Roper, M., 12
Rosazza, J. P., 223
Rose, A. F., 187
Rosenberger, M., 254
Rosenblum, M., 35
Ross, A. C., 255
Ross, P. E., 291
Rossi, C., 37, 69
Rossi, J. C., 60
Rossi, T., 129
Roth, B., 98
Rothschild, K. J., 258
Rouessac, F., 31
Roush, D. M., 40, 61
Roush, W. R., 111
Rousseau, G., 63, 89
Rouwette, P. H. F. M., 44
Row, L. R., 214
Rowan, D. D., 188
Rowan, M. G., 68
Rowe, J. W., 73, 210, 232
Roy, D. N., 231
Roy, G., 20
Roy, L. N., 226
Roy, R. G., 299
Rozen, S., 41,42
Rozynov, B. V., 230
Rsai, R., 281
Rubchinskaya, Y. M., 251
Ruberto, G., 186
Rubin, M. B., 46
Rubinova, N. R., 5 5
Rucker, E., 43
Rudnick, M. S., 239
Rucker, G., 38, 181
Rueedi, P., 193
Ruel, O., 64
Ruest, L., 166
Riittimann, A., 237, 240
Ruhdorfer, J., 59
Rulko, F., 63
Rullkotter, J., 232
Ruppert, J. F., 60, 99
RUSSO,
G., 210, 328
Rustaiyan, A., 88, 146, 172
Rustidge, D. C., 75
Rutledge, P. S., 292,302,327
Ruveda, E. A., 194
Ruzicka, L., 209
RUZO,L. O., 64,74
Ryabora, K. C., 40
Ryabushkina, N. M., 33
Rybakov, V. B., 271,272
Rychlewska, U., 146
Rychnovsky, S. D., 27
Rycroft, D. S., 146, 216, 221
Rykowski, Z., 41, 49, 50, 51
Ryoshentseva, M. A., 33
Saburi, M., 253
Sadasivan, V., 41
Sadler, I. H., 121, 140
Sadowska, H., 55
Saeedi-Ghomi, M. H., 127,
128
Saengchjan, S., 266
Saenz de Buruaga, A., 199
Saga, H., 54
Sahu, N. P., 230
Sahui, R., 26
Sai, H., 190, 196
Sainton, J., 48
Sainty, D., 59
Saito, A., 85
Saito, H., 230,277,290,291
Saito, M., 16
Saito, T., 29, 141, 213
Saito, Y., 189, 266
Sakai, K., 126
Sakai, S., 232
Sakai, T., 59, 60, 70, 172
Sakakibara, J., 199
Sakan, F., 134, 136
Sakan, T., 59
Sakata, I., 32
Sakata, J., 73
Sakdarat, S., 29
Sakina, K., 59
Sakuma, K., 20, 33, 63
Sakurai, H., 16
Sakurai, N., 214,216
Salama, O., 7,, 58, 60
Salazar, J. A., 226, 308
348
Salemink, C. A., 67
Salen, G., 291, 312
Salisbury, P., 45, 48
Salisbury, P. J., 228
Salomon, R. G., 40
Sam, F. W., 31
Samaddar, A. K., 203
Samek, Z., 169, 174
Sammon, M., 287
Samokhvalov, G. I., 247,
255,261
Samsonova, V. N., 23
Samuel, O., 44
Samuelsson, G., 234
Sanchez, I. H., 103, 204
Sandberg, F., 234
Sanders, J. K. M., 273
Sandmann, G., 210, 261
Sandorfy, C., 259
Sandra, J. M., 15
San Feliciano, A., 118
Sangaiah, R., 67
Sanghui, Y. S., 67
Sanjoh, H., 29, 60
Sankaram, A. V. B., 106
Sankawa, U., 215, 277
Sannikov, 0. B., 255
Sano, H., 19,42
Sano, T., 232
Sansoulet, J., 9
Sant, P. G., 234
Santaniella, E., 295
Santelli, M., 40, 42
Santer, J. M., 247, 253
Santiago, M. L., 307
Santini, C., 142
Saplay, K. M., 26
Sarel, S., 54
Sarg, T. M., 102
Sarig, S., 271
Sarkar, A. C., 230
Sarkisian, G. M., 310
Sarma, M. R., 41
Sasaki, H., 32, 59
Sasaki, M., 63
Sasaki, S., 37, 42
Sashida, Y., 192
Sastre, B. A., 32
Sato, F., 18, 25, 44
Sato, K., 76, 89, 234, 264
Sato, M., 18, 25, 44
Sato, S., 61, 166
Sato, T., 9,30,33,36,39, 170
Sato, Y., 211
Satoh, J. Y., 295, 300, 318
Satoh, T., 172
Sattar, A., 31, 124
Saucedo, R.,190
Saucy, G., 13, 254
Sauer, G., 324
Sauer, M. J., 284
Saul, J. A., 329
Saussay, R., 72
Saussine, L., 62
Author Index
Savard, S., 193
Saverwein, P., 28
Savoia, D., 25
Savona, G., 190, 191, 225
Savu, P. M., 17
Sawada, T., 234
Sawitzki, G., 218
Sawutz, D. G., 277
Sawzik, P., 286
Sayama, S., 157
Sayed, Y., 65
Scallen, T. J., 282
Scarborough, R. M., 43
Schade, W., 279
Schafer, H.-J., 21
Schaffner, K., 61
Scharf, H. D., 50
Scheffer, J. J. C., 44, 73
Scheidl, O., 33
Schene, A. L., 42
Schenk, H. P., 32
Schenone, P., 43, 46
Scheuer, P. J., 79, 200
Schiedt, K., 237
Schikop, T., 74
Schlatter, H.-R., 299
Schlessinger, R. H,, 161
Schlewer, G., 318
Schlosser, M., 35
Schmalle, H. W., 232
Schmidt, G., 25
Schmidt, J., 230
Schmitt, K., 286
Schmitt, P., 210
Schmuff, N. R., 43
Schneider, G., 198,303,327
Schneider, H. J., 50, 289
Schnelle, G., 8
Schnoes, H. K., 319
Schonecker, B., 273, 279,
282, 302
Schonholzer, P., 269, 318
Scholler, R., 281
Schostarez, H., 119, 129
Schouwey, M., 32
Schram, K. H., 219
Schreiber, K., 198
Schreiber, S. L., 38, 142
Schreier, P., 33
Schreiner, R., 258
Schrock, A. K., 279
Schroepfer, G. J., jun., 318
Schrott, E. L., 262
Schrott, U., 8
Schuber, F., 210
Schubert, G., 273,279
Schuelte, H. R., 4
Schulte, G., 79
Schulte-Elte, K. H., 12, 23,
28
Schulze, P.-E., 308
Schultz, A. G., 302
Schultz, G., 266
Schurig. V.,8
Schuster, A., 158, 169, 172

Schuster, R., 318
Schwack, W., 54
Schwartz, J., 312
Schwarz, M., 63
Schwedt, G., 282
Schweizer, W. B., 255
Schwenen, L., 5
Schwier, J. R., 52
Schwindeman, J. A., 52
Scognamiglio, G., 298
Scopes, P. M., 140
Scordamaglia, R., 6
Scott, W. J., 300
Scriven, F. M., 15
Sealfon, S., 21, 48
Seamark, D. A,, 282
Secord, N., 89
Seeger, A., 323
Segal, R., 62
Segal, R. A., 146
Segaloff, A., 325
Segura, M. L., 45
Seiber, J. N., 276
Seidel, I., 273
Seidler, M. D., 292
Seldes, A. M., 317
Self, C. R., 295
Selover, S. J., 202
Seltzman, H. H., 65, 66
Selva, A., 5
Semenovski, A. V., 16, 33,
252
Semmelhack, M. F., 130,161
Sen, A. K., 189
Sen, M., 230
Sendra, J. M., 32
Sengupta, P., 230
Sensen, S. R., 5
Seo, S., 209, 234, 276
Sepiol, J., 39
Sepulveda, J., 37
Serebryakov, E. P., 198
Sergent-Guay, M., 166
Sestak, Z., 256
Sethi, A. S., 39
Sethi, M. L., 15
Seto, S., 77
Setzer, S. R., 66
Sevenet, T., 222
Sgarabotto, P., 61
Shaden, G., 66
Shafiullah, 307
Shah, G. D., 65, 66
Shah, J. N., 52
Shah, S. K., 76
Shakhova, M. K., 255
Shamsuddin, K. M., 223
Shankaran, K., 38
Shanmuganathan, S., 193
Sharkov, A. V., 260
Sharma, A. S., 174
Sharma, M. L., 39, 253
Sharma, R. P., 146, 294
Author Index
Sharma, S. P., 37, 39
Sharpless, K. B., 20, 23, 27,
50
Shaw, D. J., 266
Shaw, I. M., 38,47
Shchirina-Eingoru, I. V., 48
Shea, C. M., 99, 309, 311
Shearer, M. J., 266
Shefer, S., 312
Sheldrick, G., 66
Sheldrick, W. S., 48
Sheppard, P. N., 202
Sheth, J. P., 135
Sheves, M., 247
Shewmaker, C., 277
Shiao, M. S., 70, 88
Shibaev, V. N., 264
Shibagaki, M., 252
Shibasaki, M., 136
Shibata, K., 197
Shibata, S., 15,230,234,253
Shibayama, F., 200
Shichida, Y., 259
Shido, K., 234
Shieh, H.-S., 270
Shiga, M., 59
Shimada, A., 241
Shimada, K., 142, 143
Shimizu, M., 46, 48
Shimizu, N., 63, 214
Shimokawa, T., 115
Shimomura, H., 192
Shimozuma, K., 33
Shimpo, T., 54
Shingu, T., 58, 197, 230
Shioiri, T., 19
Shiojima, K., 225
Shiota, H., 59
Shirahama, H., 49, 115, 123,
124, 126, 134, 136
Shirai, N., 199
Shirakawa, K., 234
Shiroishi, M., 256
Shishibori, T., 68, 264
Shiuey, S.-J., 318
Shkrob, A. M., 247
Shmelev, L. V., 20, 34
Shmitz, R., 66
Shmueli, U., 234
Shochet, N. R., 271, 309
Shoda, S., 21
Shoeb, A., 228
Shono, T., 64
Shoolery, J. N., 63, 106
Shoppee, C. W., 318
Shoyama, Y., 66
Shropshire, W., jun., 262
Shukla, Y. N., 60
Sicva, M., 146
Siddall, J. B., 316
Siebert, F., 260
Siefermann-Harms, D., 237
Siegman, A., 258
Siemienink, A., 43
349
Sieng, L. H., 194
Sietsema, W. K., 263
Sigurdson, E. P., 45
Sil, A. K., 231
Sillesen, A. H., 257
Silveira, A., 18
Silveira, E. R., 190
Silverman, R. B., 265
Silverstein, R. M., 36
Sim, G. A., 123, 146, 169,
193
Simes, J. J. H., 215, 225
Simmross, F. M., 44, 91
Simonov, V. I., 271, 272
Simons, S. S., 289, 298
Simpson, I. C., 198
Simpson, J. B., 69
Simpson, K. L., 235, 245,
256
Simpson, T. J., 86, 87, 88,
234
Sims, D., 174
Sims, J. J., 15, 92
Sims, R. J., 81
Singaram, B., 52
Singh, A. K., 5 , 55
Singh, H., 271
Singh, J., 206, 214
Singh, P., 146
Singh, P. N., 234
Singh, R. D., 6
Singh, S. B., 32,234
Sinnott, M. L., 197
Sinyakov, G. N., 245
Sippel, C. J., 266
Sircar, P. K., 256
Sircar, S. M., 256
Sisani, E., 194, 252
Sisti, M., 184, 194
Sivaramakrishnan, R., 295
Sjostrand, U., 312
Skattebol, L., 20
Skatovski, E. D., 33
Skeiton, B. W., 78, 182
Skorkovska, H., 231
Skorobogatova, E. V., 46
Skripiuk, 0. B., 56
Skulberg, 0. M., 238
Slack, D. A,, 22
Slade, C. J., 322, 323
Slemt, J., 281
Sloan, K. B., 275
Slougui, N., 63, 89
Smit, E. N., 73
Smith, A. B., 43,63,119,300
Smith, A. G., 281
Smith, D. H., 280
Smith, E., 256
Smith, I. H., 64
Smith, L. C., 286
Smith, L. L., 280
Smith, T. L., 164
Smoczkiewicz, M. A., 321
Smolik, R., 303
Snajbark, K., 73
Sneden, A. T., 228
Snider, B. B., 9, 21, 28, 40,
48, 61, 63, 312
Snieckus, S., 17
Snieckus, V., 63
Snowden, R. L., 91, 113
So, S., 142
Soai, K., 44
Sobotka, W., 57
Sodano, G., 79, 298, 329
Soderlund, D. M., 64
Sohani, S. V., 296
Sohar, P., 303
Sohoni, J. S., 158
Sokoloski, E. A., 60
Sokolovsky, V. Y., 262
Sokolov, V. N., 48
Sokolskii, D. V., 25, 255
Soler, A., 45
Soll, J., 266
Solladie, G., 34
Soman, R., 41
Someya, T., 32
SommC-Martin, G., 282
Sonawane, H. R., 50, 56
Sondengam, B. L., 216,221
Song, B.-H., 253
Song, C. M., 253
Sonnay, P., 91
Sonnet, P. E., 38, 283
Sonobe, T , 6 0
Sonoda, Y., 211
Sood, G. R., 58
Sorg, B., 200
Sotheeswaran, S., 226
Soti, M., 328
Sotiropoulos, J., 6, 52
Soucy, P., 45
Soulen, R. L., 39
Southwick, E. W., 63
Sowes, R. W., 74
Sozzi, G., 303
Spagnoli, N., 192
Spaleck, N., 53
Spanton, S. G., 202
Specian, A. C., 247
Speek, J., 291
Spencer, G. F.. 213, 216
Spindell, D., 40
Spiridonova, M. E., 46
Spiro, T. G., 257
Sponsel, V. M., 198
Sporn, M. B., 263
Spring, O., 146
Spronck, H. J. W., 65
Spurgeon, S. L., 235
Sree, A., 226
Srinivas, P., 67
Srinivasan, C. V., 61
Srinivasan, R., 38
Srivastava, A. K., 234
Srivastava, K. C., 234
Srivastava, R. S., 234
Author Index
350
Staba, E. J., 234
Stahle, M., 35
Stahly, G. P., 93
Stahnke, M., 308
Stampf, J.-L., 318
Stanley, P., 98
Starzemska, H., 35
Steenkamp, J. A., 62
Steglich, W., 128
Steinbach, R., 8, 92, 297
Steinberg, 1. Z., 258
Steinbuch, K., 8
Steiner, E., 64
Stenstrou, Y., 20
Stenzel, D. J., 86
Stepanova, T. P., 286
Stephenson, D. F. M., 299
Stephenson, G. R., 44
Sterligova, G. I., 46
Stevens, E. S., 6
Stevens, K. E., 103, 139
Steyn, P. S., 172
Sticher, O., 5, 7, 58, 59, 60,
283
Stierle, D. B., 15
Still, W. C., 206
Stillman, M. J., 163
Stipanovic, R. D., 106
Stockburger, M., 258
Stockis, A,, 28
Stoeckenius, W., 259, 26)
Stoessl, A., 163
Stork, G., 102, 206
Stothers, J. B., 163, 276, 307
Strand, M. R., 77
Straws, C. R., 14, 15, 27
Streckenbach, B., 272,273
Stribel, M. P., 4
Strong, P. D., 270, 271
Struchkov, Yu. T., 6, 272
Struchkova, M. I., 16
Stryer, L., 258
Stuart, A. D., 202
Stuart, K. L., 193, 228
Stuerle, H., 255
Stuttle, K. A. J., 52
Stutts, K. J., 250
Suarez, E., 225, 308
Subbarao, G. S. R., 39, 226
Subramanian, K., 193
Suda, M., 21
Suding, H., 114, 146, 196
Sudo, A., 60
Suehara, H., 21 3
Sueiras, J., 250
Suemitsu, R., 38
Suga, K., 11,21
Suga, T., 68,69,72,234,264
Sugden, J. E., 287
Suggs, J. W., 39, 294
Sugie, Y., 91
Sugimoto, Y., 172
Suginome, H., 306, 309, 3 11
Suguro, T., 21
Suhr, H., 46
Suire, C., 183, 184
Sullivan, B., 78
Sullman, E. M., 255
Sultanbawa, M. U. S., 202,
226, 227, 228, 230
Sum, F. W., 253
Sun, H.-D., 197
Sun, H. H., 201
Sun, R. C., 13
Sun, X.-C., 197
Sundar, N. S., 39
Sundaralingam, M., 232
Sunderaraman, P., 51
Sung, C.-K., 215
Sunko, D. E., 42, 76
Sunyawanshi, S. N., 47
Surburg, H., 183
Surcouf, E., 272
Suri, S. C., 193
Suseela, K., 192
Suterjadi, A., 60
Sutherland, M. D., 59
Suwita, A., 67, 88, 146
Suyunbaev, U., 255
Suzukamo, G., 46
Suzuki, H., 22, 259
Suzuki, K., 29, 54, 252
Suzuki, M., 111
Suzuki, S., 200
Suzuki, T., 21, 88, 99, 157,
258,259, 320
Svendsen, A. B., 44, 64, 73
Svovoda, G. H., 59
Swanson, B. N., 263
Swanson, S., 98
Swayze, J. K., 293
Sweeney, J. G., 294
Swenson, D. C., 271
Swern, D., 288
Swiatek, L., 59
Swiger, A. A., 36
Swindells, D. C. N., 271
Sykes, P. J., 327
Szabolcs, J., 256
Szalontai, B., 258
Szczepanski, A., 46
Szczepek, W. J., 305
Szeleczky, Z., 328
Taarit, Y. B., 33
Tabata, T., 232
Taber, D. F., 34
Taber, H. W., 266
Tada, M., 33, 170, 172
Tagawa, M., 58, 59, 60
Tagle, B., 127, 183, 202
Taguchi, H., 32, 59
Taira, Z., 158, 172
Takabe, K., 30,251
Takabe, S., 234
Takada, M., 266
Takagaki, T., 290
Takagi, H., 273

Takagi, K., 33, 51
Takagi, S., 59, 256, 277
Takagi, T., 256
Takagi, Y., 15, 238
Takahara, Y., 74
Takahashi, H., 43
Takahashi, K., 15, 32, 41,
141,230,234
Takahashi, M., 22, 232
Takahashi, N., 197
Takahashi, T., 33, 143, 170,
172, 211, 223, 226
Takahashi, T. T., 300
Takahashi, Y., 311
Takaki, K., 70
Takaksuto, S., 316
Takami, M., 62
Takane, S., 206
Takano, S., 38
Takase, K., 157
Takashi, I., 274
Takayama, H., 319, 320
Takayama, M., 230
Takayanagi, H., 5, 50, 51,
160
Takazawa, O., 85
Takeda, A,, 33, 38, 60
Takeda, R., 158, 183, 184
Takeda, T., 234
Takeda, Y., 59, 60, 61, 70,
181,197
Takei, S., 206
Takemoto, T., 73, 85, 158,
172,183,184
Takemura, K. H., 185
Takenaka, S., 287
Takeo, T., 15
Takeshita, H., 130
Taketomi, H., 42
Taki, M., 59
Takigawa, T., 19
Taksuta, K., 135
Tal, D. M., 276
Talapatra, B., 227, 230
Talapatra, S. K., 227, 230
Talvitie, A., 106
Tamaru, Y., 12
Tamas, V., 245
Tamm, C., 94
Tamir, I., 66, 318
Tamura, H., 85
Tamura, M., 46
Tamura, T., 213, 214, 230,
274, 277,285
Tanabe, K., 37,42, 49, 51
Tanahashi, T., 70
Tanaka, K., 41
Tanaka, M., 46
Tanaka, N., 195
Tanaka, O., 196,234
Tanaka, S., 12, 25
Tanaka, T., 196
Tanaka, Y., 12, 256, 269
Author Index
Tandon, R., 231
Tandon, R. N., 234
Taneja, S. C., 15, 33
Tang, C. P., 271, 309
Tange, K., 69
Tani, T., 48
Tanida, K., 38
Tanis, S. P., 81
Taniyasu, S., 234
Tasumi, M., 257
Tateishi, K., 284
Tatsuno, T., 98
Tauber, J. D., 237
Tavecchia, P., 194
Taylor, D. A. H., 219
Taylor, G. J., 329
Taylor, W. G., 64
Tazawa, H., 24
Teehan, I. R., 206
Tellado, F. G., 199
Tempesta, M. S., 219
Temple, J. S., 312
Tenczer, J., 74
Tenneson, M. E., 328
Terai, T., 199, 231
Ternai, B., 226
Terpugov, E. L., 260
Terra, W. R., 238
Terui, Y., 276
Teutsch, G., 303, 323, 324
Texter, J., 6
Thacker, V. B., 296
Thaisrivongs, S., 205
Thakur, R. S., 32
Thaller, V., 140
Thappa, R. K., 211
Theil, F., 326
Thies, P. W., 5 , 59
Tho, N.-D., 228
Tho, Y. P., 202
Thomas, A. F., 3, 32
Thomas, D. M., 60
Thomas, H., 59, 62
Thomas, J. A., 98
Thomas, M. T., 17, 63
Thommen, W., 14
Thompson, M., 70
Thomson, R. H., 80
Threlfall, D. R., 266
Thyagarajan, G., 146
Tice, C. H., 177
Tietze, L.-F., 5,6,61,66,70,
177
Tilchourova, L. A., 46
Tillman, A. M., 129
Timms, R. N., 295, 318
Timoney, R. T., 73
Timoshina, T. N., 56
Tingoli, M., 324
Tint, G. S., 291, 312
Tishchenko, V. G., 272
Tius, M. A,, 53, 204
Tiwari, K. P., 234
Toda, H., 52
351
Toda, S., 264
Toder, B. H., 63
Toeplitz, B. K., 272, 293
Toia, R. F., 189
Tokoroyama, T., 201
Tokubuchi, N., 203
Tokunaga, F., 260
Toledo, F., 146
Tolstikov, G. A., 12, 48
Toma, L., 328
Tomasik, W., 299
Tomb, F., 118
Tome, G., 5
Tomimatsu, T., 203
Tomimori, T., 234
Tomita, B., 105
Tomita, K., 165
Tomita, M., 36
Tomita, Y., 209
Tomoda, S., 130
Tomosue, K., 48
Tomuro, Y., 25
Tonnesmann, U., 74
Toome, V., 277
Torelli, V., 321
Tori, K., 50, 170, 209, 234,
276
Tori, M., 94
Torii, S., 14, 24, 60, 99, 160,
253
Toromanoff, E., 286,288
Torres, C., 32
Torres-Martinez, S., 262
Tosi, C., 6
Toth, J. A., 200
Toth, K., 13
Towner, P., 259, 260
Townsley, P. M., 228
Toyota, M., 73,85, 158, 172,
183, 184
Tozyo, T., 234
Trabucco, A., 329
Trafford, D. J. H., 282
Traldi, P., 5
Tramell, M., 246
Tramontano, A., 8
Tran-Viet, D., 61
Trave, R., 61
Traynor, S. G., 14, 20, 33,
41, 44, 45, 50
Trehan, I. R., 18, 21
Trehan, N., 253
Treppendahl, S., 46
Tresselt, D., 273
Trifilieff, E., 181
Tringali, C., 186, 201
Tripathi, R. D., 234
Trius, A., 12
Trivedi, G. K., 102, 104
Trivino, A., 12
Trka, A., 279
Troffer, J., 6
Trogolo, C., 5 , 58, 59, 61
Trombini, C., 25
Trost, B. M., 23,43, 60, 294,

307
Trouilloud, M., 280
Tsai, T. Y. R., 311, 325
Tsankova, E., 172
Tseikinskii, V. M., 271, 272
Tskhovrebachvili, T., 10
Tsuboi, S., 33, 60
Tsubota, N., 284
Tsubuki, M., 314
Tsuda, M., 259
Tsuda, Y., 232
Tsuhako, A., 13
Tsuji, J., 22
Tsuji, M., 325
Tsuji, T., 31
Tsujimoto, K., 247, 260
Tsujino, Y., 85, 252
Tsujisaka, Y., 14, 72
Tsukitani, Y., 200
Tsunaga, K., 48
Tsuneyawa, T., 59
Tsuno, Y., 63
Tsuruta, H., 54
Tsutsumi, K., 63
Tsuyuki, T., 226
Tsuzuki, K., 100, 121, 136
Tucker, D. J., 228
Tulshian, D. B., 93
Tumlinson, J. H., 38
Turecek, F., 280,294
Turganbaeva, S. M., 25
Turner, B. L., 4
Turner, C. E., 65,66,70, 174
Turner, J. V., 195, 199, 205
Turner, R. V., 262
Tursch, B., 114, 202
Twine, C. E., 65
Twitchin, B., 199
Tyler, M. I., 200
Ubik, K., 169
Uchida, M., 62
Uchida, N., 264
Uchida, T., 311
Uchio, Y., 48, 187, 199
Uda, H., 5, 63, 277
Ueda, H., 33,77
Ueda, S., 57
Uegaki, R., 163
Ueno, A., 197
Ueno, Y., 19,42, 62
Uesato, S., 59
Uijttewaal, A. P., 34
Uliss, D. B., 65, 66
Ulkus, R. A., 258
Ullah, Z., 98
Ulubelen, A., 193
Umani-Ronchi, A., 25
Unemoto, T., 256
Uneyama, K., 14,24, 253
Unnikrishnan, P., 65, 66
Uno, T., 52
Author Index
352
Untch, K. G., 289
Uobe, K., 59
Urata, M., 41
Urbanovich, T. R., 55
Ushminder, K., 14
Uskokovic, M. R., 312, 318
Utaka, M., 38
Uto, S., 183
Uvarova, N. I., 216
Uyehara, I., 20
Uyehara, T., 141, 203
Uzar, H. C., 61
Uzarewicz, A., 49
Uzarewicz, I., 35, 49
Uzawa, J., 277
Vakhrameeva, A. A., 55
Vakulova, L. A., 247, 261
Valasinsky, V. F., 6
Valencia, A., 190
Valenta, Z., 271
Valente, L. M., 192
Valentine, D., 13
Valero, M. J., 37, 40
Valimae, T., 15
Valisolalao, J., 21 1
Vallen, S., 8
Valverde, S., 191, 192, 193,
199
van Audenhove, M., 39, 161
van der Gen, A., 34
Vander Meer, R. K., 77
Van de Ven, M., 258
Vandewalle, M., 39, 61, 161,
178, 179
Van Doorn, M., 204
Vanek, T., 174
van Engen, D., 60, 127
Vanhaelen, M., 282
Vanhaelen-Fastre, R., 282
van Leeuwen, P. W. N. M.,
33
van Leusen, A. M., 44
van Leusen, D., 44
Van Meerssche, M., 114,
202, 228
Van Noort, P. C. M., 255
van Os, F. H. L., 60
van Straten, J., 63
Van Tri, M,, 222
van Vliet, N. P., 307
Varaprath, S., 11
Varenne, J., 156
Varkey, T. E., 177
Varma, R. K., 272, 293
Vasanth, S., 146
Vasilyuk, S. M., 62
Vathke-Ernst, H., 40
Vaughan, K., 121
Vaultier, M., 307
Vazeux, M., 4, 5
Vecchi, M., 237, 240, 255
Veeman, G. E., 286
Veeravalli, J., 62
Veierov, D., 309
Velenyi, L. J., 35
Venkatesan, K., 193, 270,
27 1
Venkateswaran, R. V., 204
Venuti, M. C., 110
Venzke, B. N., 213
Vereshchagin, A. N., 56
Verghese, J., 4, 32, 41, 55
Vergottini, R. A., 271
Verhoeven, T. R., 23
Verma, K., 58
Verma, N. K., 253
Verma, 0. P., 4
Verma, S. M., 5
Vermeer, P., 19, 78
Vettel, P. R., 103
Vetter, U., 15
Veysoglu, T., 19, 293
Via, D. P., 286
Vial, M. V., 72
Viallefont, P., 114
Vickery, B., 4
Vickery, M., 4
Vidal, J. P., 60
Vidari, G., 135, 207, 223
Vig, 0. P., 18,21,37,39,206,
253
Vig, R., 18,206
Vignudelli, E., 5
Vijayakumar, E. K. S., 60,
192
Vijayalakshmi, K. U., 60
Vile, J. P., 28
Vilkas, E., 48
Vilkas, M., 48
Villarreal, R., 146, 158
Vincent, P., 327
Vincien, F. F., 5
Vinogradov, L. I., 33
Vinson, S. B., 77
Viola, F., 215
Virgili, A., 12
Visser, C . P., 255
Viswanathan, N., 227
Vita-Finsi, P., 135
Voelter, W., 225
Vogel, M. K., 12
Voight, S., 4
Voigt, B., 198
Vokoun, J., 279
von der Eltz, H., 61
Von Dreele, R. B., 78
von Kiedrowski, G., 66
von Rudloff, E., 73
von Schantz, M., 5
Von Zastrow, M., 258
Voss, W., 48
Vostrowsky, O., 54
Vouros, P., 279
Vrbancich, J., 5
Vrkoc, J., 202
Vuilhorgne, M., 174
Vulfson, S. G., 6, 56
Vyazankin, N. S., 46
Vyaznikovtseva, 0. V., 25,
255
Vyrdov, V. A., 49
Vystrcil, A., 231
Wada, K., 199
Waegell, B., 5
Wagner, J., 256
Wagner, T. E., 277
Waibel, R., 58
Waineraich, M. S., 215
Waki, T., 48.
Walckhoff, B., 259, 260
Walde, A,, 35
Walden, M. K., 282
Walker, D. G., 170
Walker, D. M., 118
Walker, G. J., 292
Walker, R. P., 238
Walkinshaw, M. D., 87, 88
Walkowicz, C., 56
Walkowicz, M., 56
Wallace, J. B., 60
Walter, J. A., 277
Walton, D. C., 238
Warin, R., 226
Warkentin, J., 46
Warnhog, E. W., 276,307
Warshel, A., 258
Wasiowich, C. A., 18
Wasserman, H. H., 294
Wasylishen, R., 4
Watanabe, A., 50
Watanabe, F., 284
Watanabe, H., 18
Watanabe, K., 66, 76
Watanabe, M., 155
Watanabe, S . , 11, 21
Watson, F. E., 271
Watson, S. W., 42
Watson, T. R., 276
Watson, W. H., 115, 196
Watson, W. P., 37
Wazeer, M. I. M., 228, 230
Weakley, T. J. R., 98
Weavers, R. T., 203
Webb, R., 283
Webster, M., 290
Weedle, M., 42
Weedon, B. C. L., 241
Weeks, C. M., 270
Wege, D., 110
Wegerstahl, P., 44
Weigand, E. F., 50
Weihe, G. R., 323
Weiler, E. W., 284
Weiler, L., 31
Weinberg, M. L. D., 31
Weinges, K., 61
Weiss, R. M., 258
Weissberger, E., 28
Author Index
Weiter, L., 253
Welch, S. C., 93, 99
Wells, R. J., 15, 201, 234
Welmak, M., 46
Welniak, M., 46
Wender, P. A., 103
Wenderoth, B., 8
Wendisch, D., 174
Wenkert, E., 192
Wenzel, M., 286
Werbin, H., 265
Werstiuk, N. H., 7, 45
West, J. W., 53
West, T. F., 64
Westbrook, E., 272
Westermann, J., 8, 92, 297
Westfall, S. S., 256
Westmijze, H., 19, 78
Westmore, J. B., 279
Westwood, N. P. C., 7
Weyerstahl, P., 11, 91
Whelan, J. K., 73
Whitaker, B. D., 262
White, A. H., 78, 182, 188,
189,202,226
White, J. D., 60, 83,98,99
White, L. S., 38
White, P. S., 39, 164, 271
Whitesell, J. K., 61
Whiting, D. A,, 22
Whittaker, D., 6, 52, 54
Whittle, J. A., 177
Whybrow, D., 64, 183
Wicha, J., 325
Wichmann, J. K., 319
Wiechert, R., 308, 323, 324
Wieslander, A., 258
Wiesner, K., 311, 325
Wiggins, P. L., 20, 76
Wightman, R. M., 250, 251,
298
Wilbrandt, R., 257, 259
Wilk, M., 286
Wilkinson, R. E., 74
Wilkomirski, B., 234
Will, G., 181
Willhalm, B., 14, 32, 62
Williams, D. H., 314, 319,
320
Williams, D. L., 65, 66
Williams, E., 223
Williams, F. D., 77
Williams, H. J., 77
Williams, J. L., 64
Williams, J. R., 17, 107, 143,
155, 275, 310
Williams, P. J., 14, 15, 27
Williams, R. O., 329
Willis, B. J., 48, 89, 166
Wills, R. B. H., 15
Willuhn, G., 174
Wilson, B., 14, 15, 27
Wilson, R. S., 66
Wilson, S. R., 35, 39, 108
353
Wing, R. M., 15
Winkler, T., 5 , 58, 64
Winnik, F. M., 306
Winter, R. E. K., 140
Wirtz, G. H., 256
Witkiewicz, K., 10, 37, 40
Wodzki, W., 46
Wolf, H., 111
Wold, H. R., 26, 63, 255
Wolff, G., 309
Wolff, S., 25
Wolinsky, J., 31, 42
Wollenberg, R. H., 31
Wong, R. Y., 93
Wood, D. L., 70
Woode, K. A., 227
Woodgate, P. D., 292, 302,
327
Woodruff, W. H., 257, 259
Woods, G. F., 299
Woodward, R. B., 130
Worth, B. R., 55, 210,228
Worthington, P. A., 81
Wovcha, M. G., 328
Wray, V., 275
Wright, C. L., 324
Wright, J. L. C., 277
Wrzesien, J., 41, 49, 50
Wu, A., 17, 63
WU, R.-W., 174
WU, R.-Y., 146
WU, S.-C., 256
Wuest, H., 39, 46
Wydra, R., 211
Wynberg, H., 53
XU, Y.-L., 197
Yagen, B., 213
Yagi, A., 215
Yagihashi, F., 163
Yakovleva, I. M., 247, 261
Yamada, M., 165
Yamada, T., 30, 251
Yamada, S., 319, 320
Yamada, Y., 13,29, 60, 200
Yamahara, Y., 58
Yamagata, E., 104
Yamagishi, S., 262
Yamagiwa, S., 63
Yamaguchi, A., 256
Yamaguchi, H., 19, 251
Yamaguchi, K., 232
Yamaguchi, M., 241, 243
Yamakawa, K., 172
Yamakawa, T., 22
Yamaki, M., 59
Yamamoto, I., 64
Yamamoto, H., 10, 12, 22,
25, 37, 42, 63
Yamamura, A., 48
Yamamura, S., 91, 189
Yamasaki, K., 189,228,234,

276
Yamashita, H., 38, 199
Yamashita, K., 72, 254
Yamashita, M., 14, 38
Yamato, T., 27
Y amauchi, A., 284
Yamauchi, T., 59, 214
Yamazaki, M., 136
Yamazaki, S., 264
Yanagihara, K., 64
Yanami, T., 52
Yanez, R., 103
Yano, S., 230
Yano, T., 28, 64
Yanovskaya, L. A., 23
Yaremchenko, N. G., 55
Yaroshenko, N. I., 200
Yasuda, A., 12,25, 37
Yasuda, F., 276
Yasuda, H., 12, 16
Yasuda, M., 314
Yasuda, T., 14
Yasuoka, N., 199
Yasuzawa, T., 210, 253
Yates, P., 103, 306
Yatsu, T., 213
Yazawa, Y., 262
Yehia, A. A. I., 64
Yelle, L. M., 308
Yo, E., 35
Yokoi, K., 50, 53
Yokoi, T., 230
Yokono, T., 115
Yokota, T., 197
Yokota, Y., 5 , 277
Yokoyama, Y., 226
Yomosa, S., 251,259
Yonaha, K., 174
Yonebayashi, F., 306
Yoneda, K., 104
Yonetani, K., 189
Yonezawa, M., 234
Yorke, S. C., 15
Yoshida, K., 213
Yoshida, H., 64
Yoshida, T., 32, 54, 141
Yoshida, Z., 13
Yoshihara, H., 189
Yoshihara, T., 259
Yoshikawa, M., 48, 234
Yoshikawa, S., 253
Yoshikoshi, A., 33, 51, 52,
81, 86, 155, 165
Yoshimura, H., 66
Yoshimura, I., 179
Yoshimura, Y., 50, 209, 234
Yoshioka, M., 26
Yoshizawa, T., 259, 260
Yosioka, I., 32, 59
Young, S. D., 50
Young, R. N., 5 5
Yuki, S., 92, 204
Yun, H. S., 276
Author Index
354
Yurev, V. P., 12, 48
Yurina, R. A., 48, 62
Yuzuriha, T., 266
Zabel, V., 115, 196
Zachis, M., 296
Zagalsky, P. F., 258
Zaghloul, A. M., 172
Zahra, J.-P., 40
Zahrar, J. P., 5
Zainutdinov, U. N., 188
Zalkow, L. H., 102
Zamarlik, H., 31
Zamboni, R., 135

Zamkovnei, M., 52
Zanetti, L., 239
Zard, S. Z., 321
Zaretskii, 2. V. I., 279
Zavarin, E., 73
Zawadzki, S., 250
Zderic, S. A., 8
Zdero, C., 32,62,75,88,106,
111, 116, 117, 146, 158,
172, 174, 176, 188, 189,
195
Zecchini, G. P., 296
Zeelen, F. J., 272, 307
Zeiner, H., 243

Zenk, M. H., 284
Ziegler, F. E., 178, 179
Ziegler, P., 271
Zielinski, J., 312
Ziesche, J.,88,146, 158, 169,
174, 186, 196
Zile, M., 263
Zinner, K., 238
Zintl, R., 54
Zocher, D. H. T., 215
Zollo, F., 318
Zsako, J., 245
Zundel, G., 258

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