OPTICAL ROTATORY DISPERSION

OF SOME THALICTRUM ALKALOIDS

Go P. Moiseeva, Z. F. Ismailov,

and So YUo Yunusov

UDC 547.944/945+541.653

A simple connection between the absolute configuration of the a symmet r i c center and the ro ta tory dispers ion (RD) curves has been established for the 1-benzyltetrahydroisoquinoline alkaloids. All the com- pounds belonging to the S se r ies have RD curves with two positive Cotton effects (CE), while the enantio- mer ic R compounds show two negative CEs in the 300-240 nm region [1]. In the case of the b isbenzyl te t ra - hydroisoquinoline alkaloids, the pat tern is more complex. The rule of optical superposit ion is not ob- served for them, since a contribution to the optical rotation is made not only by the two a symmet r i c cen- t e r s but also by the conformational changes around the mobile ether and methylene bonds.

In o rde r to establish definite laws connecting the s t e r eochemis t ry and nature of the optical ro ta tory dispers ion of the bisbenzyltetrahydroisoquinoline alkaloids, we have recorded the RD curves of thalsimidine (I), thalsimine (H), hernandezine (III), thalisopine (IV), thalmine (V), O-methylthal icberine {VI), thalfoeti- dine (VII), the benzylisoquinoline-aporphine alkaloid foetidine (VIII), and the aporphine thalicmidine (IX). The configurations of all these alkaloids have been established by chemical methods [3, 4, 6, 8, 13, 14].

The bisbenzyltetrahydrotsoquinoline alkaloids possess anomalous RD curves with CEs in the 320- 240 nm region (Figs. 1 and 2). The UV spect ra of the bisbenzyltetrahydroisoquinolines have two absorption bands due to the p resence of the a romat ic chromophore: the f i rs t of medium intensity (~ 6,000-10,000) at 282 nm and the second, s t ronger , band, that of an allowed 7r ~ 7r* t ransi t ion at 206 nm (~ 80,000-130,000) with a shoulder at about 225-238 nm.

The f irs t CE is connected with the a romat ic absorption band at 282 nm. Craig et al. [2] considered a connection of the second CE with the UV absorption in the 230 nm region more likely than with the s t rong band at 206 nm, as suggested by Bat tersby [1]. Craig based his conclusion on information f rom c i rcu la r d ichro ism. We have succeeded in recording the f irst ex t remum of the second CE only for cer ta in alkaloids.

F rom the nature of their rota tory d ispers ions , thalsimidine (I) and thalsimine (II) may be considered as simple benzyltetrahydroisoquinolines for which the positive CE confirms the S configuration. The C = N chromophor ic group increases absorption in the region of the f i rs t optically active band because of the r ~* t ransi t ion in the benzene r ing with the n --* n* transi t ion of the C =N bond. Because of the smal l angles of rotation and the s t rong absorption, their RD curves were recorded only down to 290 nm (see Fig° 1).

Hernandezine (III) is fair ly easi ly obtained f rom substance II. Thus, both the dimensions and the con- figuration of the dioxide r ing do not change in this p rocess and the increase in the molecular rotation of hernandezine as compared with II shows that the second asymmet r i c center also has the S configuration.

OOH 3

LC.j-o Ill vii

Institute of the Chemis t ry of Plant Substances, Academy of Sciences of the Uzbek SSR. Transla ted f rom Khimiya Pr i rodnykh Soedinenii, No. 6, pp. 705-708, November-December , 1970. Original ar t ic le submitted June 19, 1970.

© 1973 Consultants Bureau, a division of Plenum Publishing Corporation, 227 g/est 17th Street, New York, N. Y. 10011. All rights reserved. This article cannot be reproduced for any purpose whatsoever without permission of the publisher. A copy of this article is available'from the publisher for $15.00.

715

'5 k 25

1 I',\ \ I ~=H

~-5 iV

lJU H L ' ~ ° ""H -20 o ~ "

-25 ~ IV

?50 350 ~t58 558 .,!,n

~o

5o

,¢o

3o

-32

-.48

250

H" P ]~

gl

Fig. 1 Fig. 2

Fig. 1. RD curves of thalsimidine (I), thalsimine (II), hernandezine (III), and thalisopine (IV).

Fig. 2. RD curves of thalmine (V), O-methylthal icberine (VI), and thalfoetidine (VII).

45 [1_ 30 q ?5 J ~ IL

~ . . . . . . . . . .

-fO k " "~0 ~ "~-C"~

25o 35~ ~'~ ~:o ~, nm

Fig. 3. RD curves of foetidine (VIII) and thalicmidine (IX).

The cleavage of thalisopine (IV) with sodium in liquid ammonia showed that the a symmet r i c center B has the S configuration, and the S configuration has been ascr ibed to the second center of a s y m - metry , A, on the basis of NMR spect ra [6]. A measurement of the ORD of IV showed that in the 275 and 245 nm regions (see Fig. 1) there are two negative CEs, although, according to Bat tersby [1], in alkaloids of the type of oxyacanthine withanSS configuration there should be two positive CEs on a negative background.

The RS configuration has been proposed for thalmine (V) [7] and the SS configuration for O-methylthal icberine (VI) on the basis of NMR spect roscopy. In a study of the cleavage products , the SS configuration was found for V and VI. F rom the nature of the RD curve, the SS configuration is more likely for thalmine. Both alka- loids (V and VI) have RD curves with pos i t ive CEs differing only in amplitude (see Fig° 2). The considerable increase in the amplitude of the CE of VI as compared with V is possibly connected with a de- c rease in the size of the internal dioxide ring f rom 21- to 19 -mem- bered.

A Cotton effect of approximately the same amplitude as in thalmine but of opposite sign appears in thalfoetidine {VII) in the 290 nm region. The RS configuration has been proposed for this [11].

We have measured the ORD of foetidine (VIII) (Fig. 3), the aporphine fragment of which can be r e - garded as thalicmidine {IX). The latter has an RD curve with a negative CE in the 306 nm region (see Fig. 3) and, consequently, the S configuration [12]. Foetidine also has a negative CE in the same region, but its amplitude is la rger than in thalicmidineo The increase in the amplitude of the CE could have been expected, since the benzylisoquinoline fragment in foetidine possesses the R configuration [13, 14]; a negative CE is also charac te r i s t i c for this .

E X P E R I M E N T A L 4"

The optical ro ta tory dispersions were measured on a VNIEKIPRODMASh [All-Union Scient i f ic-Re- search Experimental Design Institute for Food Machinery] SPU-M spec t ropolar imeter ; cells with thick- nesses of 1, 0.5, and 0.1 dm were used. The concentrat ions were varied between 1.0 and 0.01 mg /ml . The solvent was methanol.

716

S U M M A R Y i

For al l the b isbenzyl te t rahydroisoquinol ine alkaloids cons idered except thal isopine, posi t ive CEs a re found in the case of the SS configurat ion and negative CEs in the case of the RS configuration°

L I T E R A T U R E C I T E D

1. A . R . Ba t t e r sby et al . , J° Chem. Soc., 2239, 1965. 2o J . Co Cra ig e t a [ . , Te t r ah . , 22, 1335, 1966. 3. S. Kh° Maekh, Z. F. I sma i lov , and S. Yu. Yunusov, KhPS [Chemist ry of Natura l Compounds], 4, 393,

1968. 4. S° Kh. Maekh and S. Yu° Yunusov, KhPS [Chemis t ry of Natura l Compounds], 1, 188, 1965. 5. M. Shamma et al . , Chem. Comm. , 7, 1966. 6. Kho G° Pulatova, S. Kh. Maekh, Z. F. I smai lov , and S. Yu. Yunusov, KhPS [Chemis t ry of Natura l C o m -

pounds], 4, 394, 1968. 7. Jo Boldas et a l . , Tet rah° Let . , 6315, 1968o 8o M. V° Telezhene tskaya , Z. F° I smai lov , and S. Yu. Yunusov, KhPS [Chemist ry of Natural Compounds],

2, 107, 1966. 9. T. T o m i m a t s u , RZhKhim., 9zh291, 1961.

10. M° Ro Falco et al . , Tet rah° Let . , 1953, 1968. 11° So Mo Kupchan et al°, Jo Am. Chem. Soc., 8._~9, 3075, 1967. 12° Co Dje ra s s i , K. Mislow, and M. Shamma, Exper . , 1_~8, 53, 1962. 13o Zo Fo I smai lov and S. YUo Yunusov, KhPS [Chemis t ry of Natura l Compounds], 2, 43, 1966. 14° Kh. S° Umarov , Z. F. I smai lov , and S. Yu° Yunusov, KhPS [Chemis t ry of Natural Compounds], 6,

444, 1970.

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