I1111111111111111Il1IR

llIlI1
l 111111111111111111
EJ52-1987-33

THE OXIDATION OF ISOQUINOLINE ALKALOIDS

WITH m-CHLOROPERBENZOIC ACID
Lu
SHENG-TEH (&&R) YANG-CKANGWu (%kE]
AND SHIOW-PIAW LEOU(mss)
School of Pharmacy, Kaohsiung Medical College,
Kaohsiung, Taiwan 8 0 7 3 1 , R . O . C .

Key Word Index-Isoquinoline alkaloids; alkaloid N-oxides; oxidation;

m-chloroperbenzoic acid (m-CPBA).

The physical properties of the A'-oxides prepared by the oxidation of tertiary

isoquinoline alkaloids with rn-chloroperbenzoic acid are presented and are compared
with those of their parent alkaloids.

About one hundred different alkaloid
N-oxides, of which thirty belong to the
isoquinoline type, have been isolated from
natural sources'-"). Among them, there
are some alkaloid N-oxides which show
significant biological activity. For example
indicine N-oxide, a pyrrolizidine isolated
from Heliotuopium indicunz (Boraginaceae),
has strong antitumor activityIs). Tubotai-
wine N-oxide an indole isolated from
Tabernamontuna holstii (Apocynaceae),
shows activity against the p-388 cell'').
But until now, to our knowledge, there is
no report on the biological activities of
isoquinoline alkaloid N-oxides. In order
to carry out the screening of the biological
activities of the isoquinoline aIkaloid
N-ox i des, thirty one tertiary i soq u i n o 1i ne
alkaloids have been oxidized by m-CPBA
in chloroform. In this paper we report
the oxidation reactions and the properties
of the products.
Though there are several kinds of
oxidizing agents (such as hydrogen
peroxide and organic peracids) which may
Scheme I
( A 1 Benz y lisoqu i noli nes :
be used for the preparation of tertiary
amine N-oxides, we chose m-chloroper-
benzoic acid (mz-CPBA) a s the oxidizing
agent") because of the facility of use, the
stability of the reagents and the good
yields of products. Thirty one isoquinoline
alkaloids (Scheme I, 1-31) were treated
with tlz-CPBA in chloroform by the method
described in the Experimental section.
T h e isoquinoline alkaloid hT-oxides (Scheme
I, la-318) were obtained and characterized
by their physical and spectral data (rnp.,
tlc, UV. 'H NMR and MS)') a s shown in
Tables 1-8. In general, the K f values in
tlc, the chemical shifts of the N-Me
groups in 'H NMR and the mass numbers
in the MS of AT-oxides are different from
those of the parent alkaloids. All of them
are new compounds except reticuline
N-oxidezl (4a), isocorydine N-oxideLa)(17a1,
glaucine N-oxide'' (18a), protopine A'-
oxide1') (19a) and atherosperrninine
N-oxide") (28a) which can be obtained
from natural sources.

Papaverine (1)
MeO-AA
MeO- II I
Ivv N
M'o-iqAN-o@
hIeO-
V W
I
G
Papaverine N-oxide (la)
I 1

J. Chin. Chem. S O C . ,34, 33-42 (1987)

34 SHENG-TEH
Lu, YANG-CHANC
Wu AND SHIOW-PIAW
LEOU

( R ) Benzyltetrahydroisoquinolines

Substituted groups
Parent alkaloids {I) A'-Oxides (11)
1 6 7 ~
3' ~~
4'
( f ) - A r m e p a v i n e (2) (fa) OMe OMe I-I OH
(+)-Armepavine (3) (3a) OMe Ohle H OH
i-)-Armepavine (4) (4a) OMe OMe 1.1 OH
(+)-Reticdine (5) 158) OMe OH OH 0 Me
(+)-Laudanidine (6) (6a) OMe OME OH OMe
(?)-N-Methylcoclaurine (7) (7s) OMe OH H OH
(+I-N-Methylcoclaurine (8) (84 OMe OH H OH

( C ) Aporphines:

Suhstututed groups
N-Oxides tion of 6a
Parent alkaloids (111)
(IV) 9 10 11 6a

(-)-N-Methylxylopine (9) OCH,O OMe H H R

(+)-Dicentrine (10) OCH,O OMe OMe H S
(-)-Nuciferine (11) OMe OMe H li H R
(i-)-N-Methylactinodaphnine (12) OCH,O OH OMe H S
(+)-N-Methylnandigerine (13) OCH,O H OH OMe s
(+)-0-Methylbulbocapnine (14) OCH,O 1-i OMe OMe S
(+)-N-Methyllaurotetanine (15) OMe OMe OH OMe €I s
. ( + ) - B o l d h e (16) OMe OH OH OMe H S
(+)-Isocorydine (17) OMe OMe H OMe OH S
(+)-Glaucine (18) OMe OMe OMe OMe H S
 THEOXIDATION ACID
OF ISOQVINOLINEALKALOIDSWITH WCHLOHOPERBENZOIC 35

( D ) Protopines:

Protopine (19)
Protopinc N-oxide 119a) ,

(19)
( E ) I’avincs:

Substituted groups
Parent alkaloids 0’) N-Oxides (VI)

(- )-Caryac hine (20) (20n) 0 ki OMe

( k)-Caryachine (21) (2la) 0 I-I OMe
( b)-0-Methylcaryachine (22) (228) OltIe 0 Me
Cr ych i ne ( =eschschol t zine) (23) (23a) OCH,O

( F) Tetrahydroprotoberberines (=berbines):

Parent alkaloids (VII) N-Oxides (VIIr) 1 Substituted groups

1 2 3 9 10

( t )-Tetrahydroberberine (24) (244 OCH,O OMe OMe

{ k ) - T e t r a h y d r o j a t r o r r h i z i n e (25) (25a) OMe OH OMe OMe
(k)-Tetrahydropalmatine (=corypairnine) (26) (268) OMe OMe OMe OMe
-. ~

( c )Spirobenzylisoquinolines:
36 SHENG-TEHLu, YANG-CHANG
Wu AND LEOU
SHIOW-PIAW

(H)Phenanthrenes:

Substituted groups
Parent alkaloids (IX) N-Oxides (XI
3 4 6 7

Atherosperminine (28) OMe OMe H H

Dicentrine methine (29) OCHzO OMe OMe
Claucine methine (30) OMe OMe OM. OMe
N-Methylxylopine methine (31) OCH,O kI OMe

Table 1. The physical data of papaverine and its N-oxide

__
i mp. ("C) MS h/z)

Papaverine (1) 147-148 339(Mt)

Papaverine N-oxide (la) HCI: 185-190 355(M+)
339(Mt-16)
338(M+-17)

Table 2. The physical data of the benzyltetrahydroisoquinolines and their N-oxides

Benz y ltetrahydroisoquinolines N-Oxides
~~

'H NMR 'H NhiR

mp. ("C) N-Me (8) MS (rn/z) m p . ("C) N-Me (6) MS ( m l d
147-148 2.60 313(Mt) 215-217 3.72 329(Mt)
313(Mt-16)
312(Mt- 17)
145-146 2.62 313(M +) 172-175 3.70 329(Mt)
313(M+-16)
312(M+-17)
148-149 2.58 313(Mt) 165-168 3.72 329(Mt)
313(Mt-16)
312(Mt-17)
ICIO,: 203-20 2.37 329(M+) 160-163 3.72 345(Mt)
329(Mt-16)
328(M*-17)
,179-180 2.51 343(Mt) 157-159 3.68 359(Mt)
343(Mt-16)
342(M*-17)
110-112 2.43 299(M+) 203-206 3.78 315(Mt)
299(Mt-16)
298(Mt-17)
114-116 2.43 299(Mt) 205-208 3.78 315(M+)
299(Mt-16)
298(M*-17)
-
 THE OXIDATIONOF ISOQUINOLINE
ALKALOIDS ACID
WITH m-CHLOROPERBENZOIC 37

Table 3. The physical data of the aporphines and their N-oxides

Aporp hines N-Oxides
'H NMR 'H NMR
N-Me (6) MS (m/z) mp. ("C) -N-Me (6) MS ( m / z )
- -
1oa- 1I o 2.52 309(M') HC 1:195- 198 3.32 325(M*)
309(Mt-16)
308(Mt-17)
162-163 2.54 339(M') 95-97 3.02 355(Mt)
339(MC-16)
338(MC-17)
165 2.54 294(M*) HC1:202-205 3.38 310(Mt)
294(M'-16)
293(M'-17)
210-212 2.57 325(Mt) 170-172 4.02 341(M+)
325(M+-I6)
324(M+- 17)
169- 170 2.53 325(M*) 233-235 3.88 341(Mt)
325(Mt-161
324(Mt-17)
129-130 2.54 339(Mt) 105-108 3.54 355(Mt)
339(Mt-16)
338(Mt- 17)
237-238 2.52 341(M+) 125-127 3.90 357iM')
341(M*-16)
340(M*-17)
161 2.58 327(M+) 155-157 3.78 343(M+)
327(Mt- 16)
326(Mt-17)
180-1 81 2.51 341(M+) H C 1 :228-230 3.50 357(M+)
341(M+-16)
340( M+-17)
120-121 2.50 355(M+) 95-97 3.92 371(M+)
355(M*-16)
354(Mt-17)

mp. ("C) IH NMR N-Me (S)! M S (m/z)

Protopine (19) 207 1.96 353(Mt)

Protopine ,%'-oxide (19a) 152-155 3.68 369(M*)
353(M+-16)
352(M+-17)

N-Oxides

174- 175 2.49 275-277 3.86 341(Mt)

325(M*-16)
324(MC-17)
(21) 241-242 2.53 325(M*) (218) 250-252 3.88 341(M+)
325(M+-lG)
324 (M+- 17)
(22) HCI:178-180 2.52 339( M t, (22a) 105-!08 3.48 355(M+)

(23) P'icrate:177 2.48 323(M+) (23a) oil I 3.50 1

339(M+-16)
338(Mt-
339(M')
17)

323(M'-161'
322(Mt- 17)
38 SHENG-TEFI Wu
Lu, YANG-CHANC AND SKIOW-RAW
LEOU

Table 6. The physical data of the tetrahydroprotoberberines and their N-oxides

Tetrah ydroprotoberines
-
MS (m/z)

168-370 339(M+) 21 0-23 3 355(M+)

339(MC-16)
338(Mt-17)
220-212 34 1(M+) 210-215
II 357(M+)
341(M+-16)
340(M+-17)
148 355(M+) 190-193 371 (M +)
355(M+- 16)
354(M+-17)

___
Dihydroochotensimine (29) I 93-94 2.52 367(M+)
Dihydroochotensimine N-oxide (278) 35-40 3.00 383(M+)
367(M+-16)
366(M+- 17)

Table 8. The physical data of t h e phenanthrenes and. their N-oxides*

I Phenanthrenes 1 I N-Oxides

(28) (COOH),:201-203 2.37 309(M +) (28a) 80-82 1 3.36

(29)
(30)
(31)
156-258
oil
85-87
. 2.35
2.41
2.34
353(M+)
369(M+)
323(MC)
(29a)
(30a)
(314
118-120
98-100
77-79
j 3.22
;

EXPERIMENTAL E.M. Merck 7734 silica gel 60 was u zed

Melting points were determined on a
Yanaco micromelting point apparatus and
a r e uncorrected. Optical rotations were
measured on a Jasco model Dip-181 Digital
Polarimeter. Ultraviolet absorption spectra
were obtained on a Beckman model 34
Spectrophotometer. T h e 'H-nuclear mag-
netic resonance spectra were taken on a
Varian EM 360 L, 60 A3Hz Spectrometer
with tetramethylsilane a s internal standard
and chemical shifts recorded in 6 (ppnz)
units. Mass spectra were measured with
a Jeol ;IMS-D-lOO mass Spectrometer.
for column chromatography and silica1 gel
GF-254 was used for thin layer chromato-
graphy. All alkaloids a r e available in our
laboratory except (-)-nuciferine and
(+)-boldine. nz-Chloroperbenzoic acid
(nz-CPBA) was purchased from Wako Pure
Chemical Industries, Ltd., Japan. '
General procedure for the rn-CPBA oxida-
tion of isoquinoline alkaloids (1-31)
The chloroform solution of wz-CPBA
(0.75 g , ca. 0.0045 snol ) was gradually added
to the chIoroform solution of the

THEOXIDATIONOF ISOQUINOLINEALKALOIDS WITH m-CHLOROPERBENZOIC
isoquinoline alkaloids (0.50 g) (1-31) with
stirring a t room temperature. The
stirring was continued f o r l h r , and then
the mixture was heated to reflux on a
water bath for 1-2hrs. The conversion of
the starting materials into their N-oxides
was determined by tlc; the solvent system
was CHCl,:MeOH=6:1. After cooling the
reaction mixture was passed through a
silica gel column and eluted with
chloroform in order to remove the
unchanged base, m-CPBA and m-chloro-
benzoic acid. Methanol was then used as
eluent t o collect the N-oxide. The
methanol eIuent was concentrated to
remove the solvent under reduced pressure.
The residue was again purified by SiO,
column chromatography (solvent: MeOH)
or by recrystallization. For ( - ) - N -
methylxylopine (9), (+)-dicentrine (10) and
(-)-nuciferine (ll),the reflux process was
omitted, and in the concentration process
the methanol eluent is not heated. The
yieIds of the isoquinoline alkaloid N-oxides
were in the range of 20-85%.
The physical data of the N-oxides
Papaverine N-oxide (la): Oily base,
'H NMR (CF,COOW): 8 3.98 (9H, s,OMex3),
4.02 (3H, s, OMe), 6.26 (lH, s, R-5), 7,OS (1H.
s, H-8) and 7.22 (5H, nt, H-3, 4, 2', 5', and
6'). Hydrochloride: colorless prisms, mp.
185-190" (Me,CO-MeOH). [aIk4+OD (MeOH,
c=O.l). U V A,, (MeOH) nnz (log E ) : 240
(4.51), 280 (3.74), 316 (4.02) and 324 (3.63).
MS 70eV, d t : 355 (M'), 339 (Mt-16), 338
(Mt-17), 324, 307, 293, 280 and 264.
dl-Armepavine N-oxide (Za): Colorless
prisms, mp. 215-217' (Me,CO-CHCl,).
[a]i4f00 (MeOH, c=O.l). UV A,,, (MeOH)
nm (log E ) : 280 (3.75). 'H NMR (CF,COOH):
6 3.73 (3H, s, NMe), 3.97 (3H, s, OMe), 4.07
(3H, S, OMe), 6.27 (IH, S, H-5), 7.09 (lH, S,
H-8) and 7.23 (4H,s, H-Z', 3', 5' and 6').
MS 70eV, m / t : 329 (M*), 313 (M+-16), 312
(Mt-17), 311, 296, 282, 270, 255, 238, 222 and
192.
L-(+)-Armepavine N-oxide (3a): Color-
less prisms, mp. 172-175" (Me,CO-CHCI,).
ACID
39
[a1~'+164" (MeOH, c==O.l). UV, 'H NMR
and MS are same as dl-armepavine
N-oxide (Za).
D-( -)-Armepavine N-oxide (4a): Color-
less prisms, mp. 165-168' (Mc,CO-CHCI,).
[a1?-24O0 (MeOH, c=O.l). UV, 'H NMR
and MS are same as dl-armepavine
N-oxide (Za).
t-(+)-Reticdine N-oxide (513): Color-
less prisms, mp. 160-163" (Me,CO-CHCI,).
C ~ r l ~ ' + l l 2(MeOH,
~ c=O.I). UV (MeOH)
nm (log E ) : 282 (3.80). 'H NMR (CF,COOH):
6 3.72 (3H, S, NMe), 4.10 (6H, s, OMex2),
6.28 (lH, S, H-5), 6.80-7.28 (4H, m, H-8, Z',
5' and 6'). MS 70ev, m / r : 345 (M'), 329
(M+-16), 328 (M+-17), 312, 298, 286, 271, 253,
239, 225, 211 and 192.
L-( +)-Laadanidine N-oxide (6a): Color-
less prisms, mp. 157-159" (Me,CO-MeOH).
[ ~ ] ~ ~ + 1 4(MeOH,
6' c=O.l). UV A,, (MeOH)
nm (log F): 280 (3.78). 'H NMR (CF,COON):
6 3.68 (3H, s, NMe), 3.72 (3H,s, OMe), 4.06
(6H, s, OMex2), 6.10 (IH, s, H-6) and
6.90-7.22 (4H, m, H-8, 2', 5' and 6'). MS
7 0 e v , m/z: 359 (M*),343 (M*-16), 342
(M+-17), 312, 311, 300, 285, 268, 253, 206 and
190.
dE-N-Methylcoclaurine N-oxide (7a):
CoiorIess needles, mp. 203-206' (MeOH).
CaJ?kOo (MeOH, c=O.l). UV A,,, (MeOH)
nm (log E ) : 282 (3.78). 'H NMR (CF,COOH):
6 3.78 (3B, s, NMe), 4.00 (3H, s, OMe-61, 6.32
(lH, s, H-6), 6.84 (lH, s, H-8) and 6.98 (4H,
s, H-2', 3', 5' and 6'). MS 70eV, m / t : 315
(Mt), 299 {M+-16), 298 (M+-17), 268, 256, 241,
223, 208, 192, 177, 165 and 107.
D-(+)-N-Methylcoclaurine N-oxide (8a):
Colorless prisms, mp. 205-208° (MeOH),
[a]Zd+42' (MeOH, c=O,l). UV, 'H NMR
and MS are same as dl-N-methylcoclaurine
N-oxide (7a).
(-)-N-Methylxylopine N-oxide (9a):
OiIy base, 'H NMR (CDCI,): 6 3.32 (3H, s,
NMe), 3.78 (33, s, OMe-9), 5.84 and 6.00
(each lH, d, J=2.OHz, OCH,O-I, Z), 6.48
(lH, S , H-3), 6.74 (IH, S, H-8), 6.78 (IH,d ,
J=lO.O Hz, H-lo) and 7.80 (lH, d , J=IO.O Nz,
€I-11). Hydrochloride: colorless needles,
mp. 195-198" (Me,CO). [&-59" (MeOH,
40 Lu, YANG-CHANCWv AND SHIOW-PIAWLEOU
SBENG-TEH
c=O.l). UV Amax (MeOH) nnt (loge): 220
(4.411, 284 (4.38). MS 70eV, m / t : 325 (M+),
309 (M+-16), 308 (M'-17), 294, 266, 208 and
164.
(-)-Dicentrine N-oxide (loa): Colorless
prisms, mp. 95-97" (MeOH). E a ] ~ - 2 O 0
(MeOH, c=O.l). UV A,, (MeOH) nllz (log E ) :
226 (4.31). 282 (4.02) and 306 (3.68). 'H NMR
(CDC1,): 6 3.02 (3H, s, NMe), 3.92 (6H, s,
OMeX2), 5.94 and 6.12 (each lH, d,
J~Z.OHZ,OCH20-1, 2), 6.52 (lH, S, H-3),
6.84 (lH, s, H-8) and 7.60 (lH, s, H-11). MS
70eV, m / t : 355 (Mt), 339 (M+-16), 338
(M+-17), 337, 296, 281, 279, 265, 251, 223, 195,
176, 165, 163 and 151.
(-)-Nuciferine N-oxide (Ila): Oily
base, 'H NMR (CDCI,): 6 3.38 (3H, s, NMe),
3.54 (3H, s, OMe), 3.84 (3W, s, OMe), 6.62
(IH, s, H-3), 7.22 (3H, m, H-8, 9 and 10) and
8.28 (lH, PIE, H-11). Hydrochloride: colorless
needles, mp. 202-205" (Me,CO). Cal~4-1820
(MeOH, c=O.l). WV A,, (MeOH) nm (log E j :
230 (4.40), 278 (4.06) and 314 (3.82). MS
70eV, . m / z : 310 (M+),294 (M+-16), 293
(M4-17); 280, 264, 252, 237, 221, 207, 194, 189,
168 and 165. -
(+)-N-Methylactinodaphnine N-oxide
(12a): Light grayish needles, mp. 170-172O
(MeOH). [al?+74O (MeOH, c=O.l). UV
Jmaz (MeOH) n m (log E): 218 (4.28), 284 (3.98)
and 310 (3.56). 'H NMR (CF,COOH): 8 4.02
(3H, s, NMe), 4.20 (3H, s, OMe), 6.30 and
6.40 (eadh lH, d, J=Z.OHz, OCH,O-I, Z),
6.90 (lH, s, H-3), 7.22 (IH, s, H-8)and 8.18
(lH, s, H-11). MS 70eV, m/z: 341 (M+), 325
(M'-16), 324 (M'-17), 310, 308, 294, 282, 267,
251, 238, 224, 165 and 152.
(+)-N-MethylnandigerineN-oxide (13a):
Light grayish prisms, mp. 233-235"
(MeOH-Me,CO). ra1?+284* (MeOH, c=O.l).
UV Amas (MeOH) nm log^): 226 (4.30), 274
(4.21) and 312 (3.48). 'H NMR (CF,COOH):
6 3.88 (3H, s, NMe), 4.00 (3IJ, s, OMe), 6.12
and 6.36 (each TH, s, OCH,O-1, Z), 7.20 (lH,
s, H-3) and 7.36 (2H, s, H-8 and 9). MS
70eV, nt/z: 341 (M+),325 (M"-16), 324
(M+-17), 323, 310, 294, 282, 266, 251, 237, 222,
209, 181, 165 and 152.
(+) - 0 - Methylbulbocapnine N-oxide
(14a): Amorphous, mp. 105-108" (Et,O).
[ ~ ~ 1 ~ ~ + 1(MeOH,
86" c=O.l). UV Am.* (MeOH)
r ~ m(log&): 236 (4.23), 274 (3.96) and 308
(3.68). 'H NMR (CDC1,): 6 3.54 (3H, s,
NMe), 3.92 (3H, s, OMe), 4.00 (3H, s, OMe),
6.02 and 6.28 (each lH, d, J=2.0 Hz,
OCH,O-1, 2). 6.88 (lH, S, H-3), 7.04 (lH, d ,
J=S.OUz, H-8) and 7.28 (ZH, d , J=S.O Hz,
H-10). MS 70 elr, m / z : 355 (M+),339 (M+-16),
338 (M+-17), 324, 309, 296, 281, 265, 251, 237,
222, 163 and 151.
(+) -N-Methyllaurotetanine N-oxide
(15a): Colorless prisms, mp. 125-127"
(CHCI,). [cr]?+102O (MeOH, c=O.l). UV
A,,, (MeOH) nm (log E): 220 (4.32), 285 (4.14)
and 312 (3.46). 'H NMR (CF,COOQ): 6 3.90
(3H, s, NMe), 3.92 (3H, s, OMe), 4.02 (6H, s,
OMex2), 6.86 (lH, s, H-3), 7.02 (lH, s, H-8)
and 8.06 (lH, s, H-11). MS 70eT/, W ' Z : 357
(M'), 341 (Mt-16), 340 (M+-17), 326, 310, 298,
283, 267, 255, 251, 240, 211, 181, 168, 152 and
139.
(+)-Boldhe N-oxide (16a): Colorless
needles, mp. 155-157" (Me,CO). ral~d+130"
IMeOH, c=O.l). UV ,Ima, (MeOH) nm (log E ) :
218 (4.43), 285 (4.12) and 308 (3.42). 'H NMR
(CE,COOH): 6 3.78 (3H, s, NMe), 3.88 (3H,
s, OMe), 4.02 (3H, s, OMe), 6.90 (lH, s, H-31,
7.04 (IH, s, H-8) and 8.04 (IH, s, H-11).
MS 70eT/, m / z : 343 (M'), 327 (M+-16), 326
(M'-17), 312, 296, 284, 269, 240, 225, 197, 181,
169, 152 and 139.
(+)-Isocorydine N-oxide (X7a): Oily
base, 'H NMR (CDCI,): 6 3.50 (3H, s, NMe),
3.78 (3H, s, OMe), 4.02 (3H, s, OMe), 4.04
(3H, s, OMe), 6.85 (IH, s, H-3) and 6.96 (2H,
s, H-8 and 9). Hydrochloride: colorless
needles, mp. 228-230" (Me,CO). [a]?+247"
(MeOH, c=0.1). UV Am.. (MeOH) nm (logE ) :
223 (4.38), 270 (4.06) and 304 (3.82). MS
7Oev, m j z : 357 (M?, 341 (M*-16), 340
(M+-17), 326, 310, 298, 283, 267, 251, 239, 196,
152 and 139.
(+)-Glaucine N-oxide (18a): Colorless
prisms, mp. 95-97' (Me,CO). [a]gf123°
(MeOH, c=O.l). UV ,Imax(MeOH) nm (log E ) :
220 (4.41), 282 (4.02) and 306 (3.84). '11 NMR
(CF,COOH): 6 3.92 (3H, s, NMe), 4.08 (12H,
s, OMeX4), 6.90 (IH, s, H-3), 7.04 (lH, s,
H-8) and 8.10 (lH, s, H-11). MS 70 eV, m / z :
371 (Mf), 355 (Mt-16), 354 (Mt-17), 340, 324,
 THEOXIDATlON OF ISOQUINOLINE ALKALOIDS
312, 297, 281, 269, 265, 165, 152 and 139.
Protopine N-oxide (19a): Colorless
needles, mp. 152-155" (MeOH). CalL4+O"
(MeOH, c=O.l). UV A,, (MeOH) nm (log E):
298 (3.98). 'H NMR (CF,COOH): 6 3.68 (3H,
s, NMe), 6.08 (4H, s, OCH,Ox2), 6.82 (lH, s,
H-4), 7.04 (lH, S, H-ll), 7.18 (lH, S, H-1)
and 7.24 (lH, s, H-12). MS 70ev, w / z : 369
(M'), 353 (M*-16), 352 (M+-17), 322, 310, 281,
267, 252, 206, 175 and 148.
(-)-Caryachine N-oxide (20a): Colorless
prisms, mp. 275-277" (EtOH). Iru1?-308"
(MeOH, c=O.l). UV A,, (MeOH) mn (log E ) :
225 s h (4.12) and 290 (4.04). 'H NMR
(CF,COOH): 6 3.86 (3H, s, NMe), 4.10 (3H,
s, OMe), 6.08 (ZH, s, OCH,O), 6.70 OH, s,
H-l), 632 (lH, s, H-4), 6.90 OH, s, H-7) and
6.98 (lH, s, H-10). MS 70eV, I H / Z : 341 (M+),
325 (MS-16), 324 [Mt-17), 310, 295, 281, 218,
190, 188 and 175.
dl-Caryaehine N-oxide (21a): CoIorless
prisms, mp. 250-252" (MeOH). Ea1%O0
(MeOH, c=O.l). UV, 'H NMR and MS are
same as (-)-caryachine N-oxide (20a).
(+)-Q-Methylcaryachine N-oxide (22a):
Amorphous, mp. 105-108' (Et,O), [a1:+159"
(MeOH;c=O.l). UV A,, (MeOH) n m (log E):
225 s h (4.22) and 289 (4.12). 'H NMR
(CDCI,):6 3.48 (3H, s, NMe), 3.90 (3H, s,
OMe), 3.92 (3H, 5, OMe), 5.98 and 6.02 (each
IH, s, OCH,O), 6.60 (ZH, s, H-l and 10 or
€3-4 and 9) and 6,72 (2H, s, H-4 and 9 o r
H-1 and 10). MS 70eV, m / t : 355 (M+), 339
(M+-16), 338 (M+-17), 324, 322, 308, 292, 204
and 188.
Crychine N-oxide (23a): Amorphous
(Et,O), [ c ~ 1 ~ - 2 0 1(MeOH,
~ c=O.l). UV Lz
(MeOH) n m (Iog E): 226 sh (4.08) and 290
(3.96). 'H NMR (CDC1,): 6 3.50 (3H, s,
NMe), 5.98 (4H, s, OCH,Ox2), 6.56 (ZH, s,
H-4 and 7 or H-1 and 10) and 6.70 (2H, s,
H-I and 10 or H-4 and 7). MS 70eV, m/z:
339"(M+), 323 (M+-16), 322 (M+-17), 308, 292,
235 and 188.
(k)-Tetrahydroberberine N-oxide (24a):
Colorless needles, mp. 210-213" (Me,CO).
[ar]~'+O" (MeOH, c=O.l). UV ,Imaz (MeOH)
nm (log E ) : 283 (4.02). MS 70 eV, m/z: 355
(MS), 339 (M+-16), 338 (Mt-17), 322, 307, 292,
278, 174, 164 and 149.
WITH m-CHLOROPERBENZOIC ACID 41
(k)-Tetrahydrajatrorrhizine N-oxide
(25a): Colorless prisms, mp. 210-215"
(MeOH-CHCI,). ra1?50" (MeOH, c=O.1).
UV ,Imax (MeOH) nnz (log E ) : 282 (3.96). MS
70el/, m / z : 357 (M+), 341 (M+-16), 340
(Mt-17), 339, 324, 309, 294, 280, 265, 164 and
149.
(&)-Tetrahydropalmatine N-oxide (26a):
Colorless needles, mp. 190-193" (MeOH).
[&&O* (MeOH, ~0.1).UV A,,, (MeOH)
nm (log E): 282 (4.02). MS 70 el/, m / z : 371
(M+), 355 (M+-16), 354 (M+-17), 338, 324, 308,
294, 278, 190, 164 and 149.
Dihydroochotensimine N-oxide (27a):
Colorless prisms, mp. 35-40: (MeOH).
[a$+OO (MeOH, ~ 0 . 1 ) . UV Amas (MeOH)
nn2 (log E): 278 (3.96). 'H NMR (CDCl,): 6
3.00 (3H, s, NMe), 4.10 (3H, s, OMe), 4.18
(3H, s, OMe), 6.28 (ZH, s, OCH,O), 6.98 (lH,
s, H-I) and 7.12 (3H, s, H-4, 11 and 12).
MS 70el/, m / t : 383 (Mt), 367 (Mt-16), 366
(M*-17), 335, 324, 308, 293 and 206.
Atherosperminine N - oxide (28a):
Colorless needIes, mp. 80-82" (Me,CO).
l i J ~ _ + o(MeOH,
o c=O.l). UV A,, (MeOH)
nm (log E ) : 213 (4.32), 234 (4.46), 252 (4.64),
258 (4.70), 279 sh (4.02), 304 (4.061, 313 (4.061,
346 (3.52) and 364 (3.54). '€3 NMR (CDC1,):
6 3.36 (6H,s, N(Me),), 3.95 (3H, s, OMe), 4.04
(3R, s, OMe), 7.31 (IH, s, H-Z), 7.46-7.98 (5H,
m, H-6, 7, 8, 9 and 10) and 9.54 (IH, m,
H-5). MS 70eT/, m / z : 325 (M', non
detectable), 264 (M+-61), 249, 233 and 217.
Dicentrine methine N-oxide (29a):
CoIorless microneedles, mp. 98-100"
(Me,CO). C c t ~ l ? k O O (MeOH, c=O.l). UV
Amex (MeOH) n m (log €1: 214 (4.28). 236 (4.42),
254 (4.61). 258 (4.68), 279 sh (4.001, 304 (4.04).
315 (4.05), 346 (3.51) and 364 (3.52). 'H NMR
(CDCI,): 6 3.22 (6H, s, N(Me),), 4.00 (3H, s,
OMe), 4.02 (3H, s, OMe), 6.28 (2H, s, OCH,O),
7.26 (IH, S, H-2), 7.32 (IH, S, H-8), 7.70 (IH,
d, J=lO.OHz, H-9), 8.00 (IW, d. J=TO.OHz,
H-10)and 8.88 (lH, s, H-5). MS 70eV, m/z:
369 (M*, non detectable), 308 (Mt-61), 293,
277, 262, 247, 245 and 139.
Glaueine methine N-oxide (30a):
Colorless prisms, mp. 118-120" (Me,CO).
Cal:4k00 (MeOH, c=O.1). UV R,, (MeOH)
42 Lv, YANG-CHANGWu AND SHIOW-PIAW
SBENG-TEB
nnz (log 6 ) : 216 (4.18), 234 (4.38), 254 (4.52),
253 (4.53), 278 s h (3.96), 304 (4.001, 313 (4.00),
346 (3.46) and 364 (3.48). 'H NMR (CDCI,):
6 3.28 (6H, s, N(Me),), 3.92 !3H, s, OMe), 4.02
(6H, s, OMexZ), 4.04 ( 3 H , s. OMe), 7.04 (lH,
S , H-8), 7.36 (lH, S, H-Z), 7.72 (lH, d,
J=lO.OHz, H-9), 8.02 (IH, d, J=~O.OHZ,
H-10) and 9.58 (lH, s, H-5). MS 70eV, m / z :
385 (M+, non detectabIe), 324 (M+-61), 309,
293 and 277.
N-Methylxylopine methine N-oxide
(31s): Colorless needles, mp. 77-79' (Me,CO).
Tal240' (MeOH, c=O.l). U V A,,, (MeOH)
~ Z W Z(log E): 215 (4.38), 236 (4.48), 256 (4.68),
258 (4.741, 278 s h (4.03), 304 (4.081, 313 (4.081,
346 (3.54) and 364 (3;56). 'H NMR (CDCI,):
6 3.28 (6H, s, N(Me),), 3.90 (3H, s, OMe), 6.12
(ZH, S, OCH,O), 7.06 (lH, S, H-2), 7.22-7.84
(4H, m, H-6, 8, 9 and lO).and 8.92 (lH, m,
H-5). MS 70eI/, m / z : 339 (M+, non
detectable), 278 (Mt-61), 263, 247, 231, 205
and 176.
Acknowledgement: We thank Prof.
C.M. Chen, Tsing Hua University, for t h e
mass measurements, and Prof. T. H. Yang,
Taipei Medical College, for the sample of
(-)-nuciferine, Prof. J. P. Rosazza,
University of Iowa, for t h e sample of
(+I-boldine.
REFERENCES
J.D. Phitlipron and S.S. Handa, t l o y d i a (1.
Nu!. P r o d . ) , 41, 385 (1978).
S. Dargupta, A. 8. Bay, S. K. Qhattacharya
and R. Base, J . N U I . P r o d . , 4 2 , 399 (1979).
M.6. Kiryakov, D. W. Hugbes, 8. C. Nalfiah
LEOU
and D.B. MscLean, Conad. J . C h e m . , 57,
53 (1979).
S. U. Karimova, I. A. Israilor, M. S. Yunusov
and S. Y. Yunusov, Khim. Prirod. Soedin.,
224 (1980) [Chem. A b s t r . , 93, 1105639 (1980)l.
P. Wiriyachitra end B. Phuriyakorn, Arcsfral.
1. C h e m . , 34, 2001 (1981).
P. 0. Owusu, 0.J. SlatLin, J. E . Knopp and
P.L. Schiff, Jr., J . N U I . P r o d . , 4 4 , 61
(1981).
V. B. Chervenkova, N.M. Mollov and S.
Paszyc, Phytochemistry, 20, 2285 (1981).
M. H. Sarragiotto, H.L. Filho and A. J .
Marsaiol, Canad. J . C h e m . , 59, 2771 (1981).
S . Pummangura, Y. A. H. Mohamed, C. J.
Chang and J. L. Mclaughlin, Phyfochemistr.v,
21, 2375 (1982).
K. lwara, M. Okada and N. Takao,
Phytochemistry, 22, 627 (1983).
A.D. EL-Shabrawy, P.L. Schiff, Jr., D. J.
Slatkin, B. D. Gupta, A. B. Ray and V. J.
Tripathi, Heterocycles, 22, 993 (1984).
J. E. Leet, A. J. Freyr, R.D. M i n a r d and M.
Shamma, J . Chern. SOC. Perkin. Trans. I ,
651 (1984).
R. Hocquemiller, C. Debitus, F. Rollot, A.
Cave and H, Jacquemin, J . N a t . P r o d . , 47,
353 (1984).
A.U. Rahman, S. Malik, S. Ahmad, I.
Chaudhary and W. U. Rehman, ffererocycles,
23, 953 (1985).
M. Kugelman, W.C. Liu, M. Axelrod, T. J.
McBride and K.V. Rao, L[oydia ( 1 . N a t .
P r o d . ) 39, 125 (1976).
0.G. 1. Kingston, F. lonercu and BAT. Li,
LIoydio ( J . N a f . P r o d . ) 40. 215 (1977).
J. C. Craig and K. K. Purushothaman, J . Qrg.
C h e m . , 35, 1721 (1970).
A. Karimov, M.V. Telezhenetskaya, K, L.
t u t f u l l i n and S. Y. Yunusov, Khim. Prirod.
Soedin., 419 (1978) [Chem. Absfr., 89,
126171n (1973)l.
(Received Augurr 2 6 , I 9 8 6 ) .