Elaeocarpus Alkaloids. The Synthesis of dl-Elaeokanine-Aand dl-Elaeokanine-C.

Joseph J. Tufariello* and Sk. Asrof Ali

Department of Chemistry
State University of New York at Buffalo
Buffalo, New York 14214
Abstract - The synthesis of dl-elaeokanine-Aand dl-elaeokanine-Cis
described by an approach which utilizes a nitrone cycloaddition to generate a B-aminoketone,which upon annulation
produces one or the other of the title alkaloids depending
upon conditions.
We wish to describe herein a synthetic entry into the Elaeocarpus family of alkaloids, a
relatively new class of indolizidinealkaloids isolated from the leaves of large, spreading
trees indigenous to New Guinea and India."*

Some of the more common members of this class of

alkaloids include elaeocarpine (&), isoelaeocarpine(2_),and isoelaeocarpicine(a), representative of the aromatic Elaeocarpus alkaloids. The leaf alkaloids derived from Elaeocarpus
kaniensis Schltr., a large tree found in the rain-forests of New Guinea, contains none of the
more connnonindolizidinealkaloids (e.g., 1, 2, or 2).

Instead, the less complex, but

obviously biogenticallyand chemically related, alkaloids elaeokanine-A (4) and elaeokanine-C

3
(3) are representativeof the alkaloidal composition.
As part of our synthetic objective to construct a number of these systems with a
common synthetic design, we initially chose to attack the nonaromatic alkaloids

4445

30. 46

4446

elaeokanine-A (4) and elaeokanine-C (2). The stereochemical relationshipof elaeokanine-C

and isoelaeocarpicine(3) suggested that a synthetic solution of the relative stereochemical
features of the former would suffice as well for the latter. The f+aminoketonemoiety
apparent in each of these alkaloids suggested to us the use of nitrone precursors. Indeed,
we envisioned that yet another B-aminoketone2, (cf. Scheme 1) would serve as a common
intermediate to the nonaromatic indolizidines. Thus, we have invoked the highly regioselective4 and stereoselective cycloadditionof I-pyrroline l-oxide ($) with 1-pentene
(1lO'C; sealed tube) to afford isoxazolidine2, bp 82-84C (5.5 mn), in 72% yield. The
isoxazolidinedisplays H-2 at 8 4.04 ppm (m, 1). The S-aminoalcoholg (90%) was readily

Scheme

l-i
+

I>

-O/N+

MC

derived from Z by catalytic hydrogenolysis (10% Pd/C; H2).

The desired, albeit thermally

labile, B-aminoketone2 was obtained by Jones oxidation. This ketone, bp 53-54C (0.07 mm),
was used directly without purification. When this crude 6-aminoketonewas treated with

acrolein (1 equiv.) in benzene containing potassium t-butylate (3 equiv.), a chromatographitally separable mixture (45%) of dl-elaeokanine-A(9) and an unsatured aldehyde (i.e., 11)
are formed in a 4:l ratio, respectively. The dl-elaeokanine-A (picrate mp 134-136C) exhibits
strong carbonyl absorption at 1670 cm-' (IR;

CC14) and displays NMR characteristics ((100 MHz,

CDC13) 6 0.92 (t, 3, J = 7 Hz), 1.1-2.0 (m, 5), 2.04-3.18 (m, 9), 3.44 (broad t, 1), and 6.82
lc
ppm (m, 1)) identical to those of d-elaeokanine-A.
Aldehyde 11, picrate mp 169-171'C dec., the alternate (i.e. to 3) aldol product derived

xn. Lh

4447

from An, exhibits its carbonyl stretch at 1660 cm-' (IR,

neat) and shows absorption (UV; 95%

EtOH) at 246 nm (e 11,930). Its NMR spectrum (100 MHz, CDC13) reveals the presence of the

F;

aldehydo proton at 6 10.12 ppm (s, 1) and the C-5 equatorial proton" as a sharp doublet at 6
3.84 ppm (J = 16 Hz).
When the crude @aminoketone 2, derived from the Jones oxidation of B is exposed to
acrolein (1 equiv.) in methylene chloride, followed (after solvent removal) by concentrated
hydrochloric acid (2h, 25(Z),there results a chromatographicallyseparable mixture (44% from
2) of dl-elaeokanine-Cand aldehyde 11, in a 3:1 ratio respectively. The elaeokanine-C.mp

69-70C, exhibits IR (CC14; 3470 and 1710 cm-') and NMR (100 MHz, CDC13) behavior (6 0.88 (t,
3, J = 7.0 Hz), 1.0-3.2 (m, 16), 3.56 (broad s, 1, cont. dependent), and 4.16 ppm (q, 1, J =
2.2 Hz)) identical to that reported for the natural product.lc The magnitude of the coupling
constants observed for the equatorial H-7 proton supports the assigned configurationlc (cf.
w.

Interestingly,we could not detect the C-7 epimer of 2 from the acid catalyzed aldol

cyclization.
We believe that elaeokanine-C (3) is the product of kinetic, rather than thermodynamic
control, since exposure of the synthetic alkaloid to concentrated hydrochloricacid for 2 h
at 25'C leaves it unaltered. An NMR examination of the product derived from this acid
treatment shows the absence of both aldehyde ii, a product which would be anticipated if the
aldol process were reversible, and elaeokanine-A. Indeed, the NMR spectrum so obtained is
virtually identical to that of the starting material.

H30+
a

I0 -

It is our belief that the arrival

o&-Pr
5a

at the transition state for the IQ + 2 process is facilitated by hydrogen bonding involving
the enolic hydroxyl function (cf., 10e) and the aldehyde carbonyl. The aldol closure of
19~ directly affords 2 with the correct relative stereochemistryat C-7, C-8, and C-9 (cf.
Z!). Indeed, such a stereospecificprocess may be involved in the biogenesis of these
alkaloids since the C-7 epimers of the Elaeocarpus alkaloids have not been reported.

AA48

Acknowledgement - We wish to thank the Institute of General Medical Sciences of the NIH for
financial assistance (GM 25303). Moreover, we are grateful to Dr. J. A. Lamberton (CSIRO,
Melbourne) for the NMR and IR spectra of natural d-elaeokanine-Aand dl-elaeokanine-C,and
for IR (KBr) spectra of the methiodide of both natural and synthetic elaeokanine-C.
References and Notes

1.

(a) S. R. Johns, J. A. Lamberton, A. A. Sioumois, and R. I. Willing, Aust. J. Chem.,

22, 775 (1969); (b) S. R. Johns, J. A. Lamberton, A. A. Sioumis, H. Suares, and
R. I. Willing, ibid., 24, 1679 (1971); (c) N, K. Hart, S. R. Johns, J. A.
Lamberton, ibid-,
8Tf (1972).

2.

A. K. Barua, C. Dasgupta, S. Chakravarti, M. K. Choudhury, and A. Ghosh,

J. Indian Chem. Sot., 22, 531 (1976).

3.

For previous synthetic efforts regarding these alkaloids, see ref. lc.

4.

Sk. Asrof Ali, P. A. Senaratne, C. R. Illig, H. Meckler and J. J. Tufariello,

Tetrahedron Lett., in press.

5.

J. J. Tufariello and Sk. Asrof Ali, Tetrahedron Lett., 4647 (1978).

6.

For a discussion of the spectral characteristicsof related systems, see T. A.

Crabb, R. F. Newton, and D. Jackson, Chem. Rev., Z_i,109 (1971).
(Received in USA $0 Juljr1979)