Department of Medicinal Chemistry, Banaras Hindu University, Varailasi, lndia
FLOWER ALKALOIDS OF ALSTONlA SCHOLARIS By S . C. DUITA, S. K. BHATTACHARYA and A. B. RAY
Abstract
Alstonia scholaris R. Br. is a large evergreen tree widely cultivated throiighout India. ~ t b e a r scompact, umbellately branched, pubescent cymes of greenish-white fragrant flowers (HOOKER,1882). The bark, leaves and fruits of the plant have been examined and alkaloids, echitamine (HAMILTON et al., 1961), echitamidine (DJERASSI e t al., 1962), picrinine (CHATTERJEE et al., 1965), rhazine (CHATTERJEE et al., 1969) and picralinal (RASTOCIet al., 1970) have been isolated and fully characterised. In an investigation designed t o yield information on the distribution and relationship of alkaloids in A. scholaris, we studied the occurrence of alkaloids in the flowers. T h e pharmacological action of the' major alkaloid, picrinine, has also been studied as a part of Our research program.
Experimental Melting points are uncorrected and were taken on a Toshniwal tneltirig poiiit npparatus in open capillary. Ultraviolet spectra were taken in aldehyde-free ethanol using Cary 14 spectrophotometer. Infrared spectra were recorded in a Perkin Elmer spectrometer mode1 257 in Nujol mull. Proton magnetic resonance (PMR) spectra were determined in deuterochloroform at 60 mHz tising Varian A-60D spectrometer and tetramethylsilane as interna1 standard. Mass spectra were run o n MS 50 instrument. Silica gel used for column chromatography refers to BDH (60-120 mesh). Column chromatography over alumina was performed with neutral grade alumina (Sarabhai M.). TLC plates were prepared with Merck silica gel G and the spots were visualised by sprayitig either ceric ammonium sulphate (CAS) o r DRAGENDORFF'S reagent. Developing solveiits iised were (4) benzeneethyl acetate (5:3) and (B) benzene-chloroform (1:l).
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The isolation of picrinine, strictamine, tetrahydroalstonine and an uncharacterised indole alkaloid is reported from the flowers of A l s t o n i a s c h o l a r i s . Picrinine, the major alkaloid, bas been found to possess central nervous system depressant action.
Alkaloids of Alstonia scholaris
87
Isolation a n d Characterisation of the Alkaloids Alkaloid ASF-1: Fraction A was dissolved in chloroform and allowed to flow through a drypacked column of alumina ( 1 5 x 4 0 cm). Elution with benzene yielded a base mixture with one major alkaloid which was separated by PLC (developing solvent: 2OIo diethylamine in benzeneethyl acetate = 2:l) and crystallised from hexane-ethyl acetate mixture as colourless needles i-ve). (130 mg), m.p. 100-OlO; RI, 0.23 in solvent A (CAS; -ve, DRACENDORFF: 213 (logs, 4.30), 262 (3.80), Lmi, 238 (3.66) nm, T h e U V spectrum of alkaloid ASF-1, A, indicated the presence of a 3H-indole chromophore and its IR spectrum showed bands for ester carbonyl (1735 cm-'), - C = N (1620 cm'') and aromatic system (1600 cm-'). T h e presence of an ethylidene group (3H doublet a t 6, 1.54 & 1 H quartet at 6, 5.52, J = 7 Hz), a methoxycarbonyl (3H singlet a t 6, 3.72) and 4 vicinal aromatic protons (4H complex multiplet between 6, 7.0-7.8) was revealed frorn its PMR spectrum. T h e mass spectrum of ASF-1 showed the molecular ion. peak a t rnle 322 (100010 abundance) and other significant peaks a t m/e 321 (60), 291 (9), 263 ( 5 9 , 234 (13), 180 (18) and 156 (10). T h e above spectral data are in perfect agreement with those reported for strictamine (1), an indolenine alkaloid (SCHNOESe t al., 1966), isolated from Rhazya strirt'r (SPITTELER-FRIEDMANN et al., 1964) and Vinca minor (TROJANEK et al., 1960). T h e identity of alkaloid ASF-1 with strictamine was established by direct comparison (rnixed m.p., superiinposable IR and Co-TLC) with authentic sample. Alkuloid ASF-2: Chromatography of fraction B over alumina and elution with benzene yielded a gum which showed two DRACENDORFF-staining spots o n a thin layer chromatoplate. T h e major as also the more polar cornponent of this base mixture was separated by PLC (developing solvent: A, CAS +- orange after 5 min) and crystallised from a mixture of hexane-ethyl acetate (9:l) as needles (3 mg), m.p. 225-27O, UV, ,lm,,225, 262 nm, MS, m/e 352 (M+, 93 per cent), 337 (100), 320 (44), 309 ( I l ) , 293 (16), 261 (16), 239 (14), 234 (20), 218 (IO), 207 (14), 206 (15), 194 (14), 181 (22), 180 (26), 168 (22), 154 (12). Insufficient material precluded characterisation of this alkaloid. Alkaloid ASF-3: T h e beiizene-chloroform eluate of the column yielding alkaloid ASF-2 afforded a pure solid (yield, 0.4 g, Rf 0.23 in solvent A, CAS + immediate orange colour changing to pink overnight). I t crystallised from methanol as needles, m.p. 21S0, UV, l.,,, (in EtOH) 237 (loge, 4.08), 287 (3.67) nm, Âmi, 223 (3.98), 260 (3.04);,,,,Â, (in 70010 HCI 104) 239 (3.65), 244 (3.65) and 306 (3.67) nm, MS, rnle 338 (M+, 36 per cent) 320 (50), 279 (20), 261 (26), 239 (100), 234 (24),
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Extraction of Alkaloids /rom thel Plant Material Flowers of A. sdîo1aris were collected from a big tree within this university campus. T h e material was dried (3.5 kg) under shade, powdered in a waring blender and extracted exhaustively first with petroleurn ether (60-80°) and then with ethanol (9.S0/o) in a continuous extractor. The alcoholic extract was concentrated to a syrup (300 ml) under reduced pressure and stirred mechanically with 7010 aqueous citric acid (1.5 1) for 6 hours. T h e acid-insoluble residue was reinoved by filtration and the-filtrate was shaken with ether ( 3 x 6 0 0 ml) to remove weak bases. T h e cornbined ether e x t r a a was partitioned with 10/o aqueous N a O H to separate phenolic bases, if any, but the alkali extract was found to be free from alkaloids and furnished only veratric acid on acidification. T h e ether layer was washed (H,O)., dried (anhydrous Na,SO,) and evaporated to yield a brown gum (3.2 g), fraction A. T h e aqueous acid left after ether extraction was rendered basic (pH, 8.5) by addition of aminotiium hydroxide and extracted again with ether. T h e ether extract was washed, dried and evaporated to dryness t o give a gummy material (5.6 g), fraction B. T h e petroleum ether e x t r a a of flowers was sirnilarly processed t o furnish a basic gurn (2.5 g), fraction C.
88
Dutta, Bhattacharya and Ray
Planta medica Vol. 30 1976
219 (14)i 218 (15), 206 (ZS), 180 (SO), 170 (27), 169 (31), 154 (37), 140 (D), 136 (26), 130 (30), 115 (30), IR, 1732 (ester carbonyl), 3410 (NH) and 1620 cm*, PMR, 3 H dd at 6, 1.54 (J=8 & 2 Hz) and 1 H m at 6, 5.48 (ethylidene), 3H s at 6, 3.75 (CO,CH,), 1 H broad signal at 6, 5.0 (-O-CH-N-) and 4H m between 6, 6.8-7.6 (ArH). The spectral properties of the alkaloid resembled picrinine (II), the major leaf alkaloid of the plant ( C H A ~ E R Jet E Eal., 1965) and direct comparison (mixed m.p., IR, Co-TLC) of the alkaloid ASF-3 with authentic picrinine established their identity.
furnished a white solid which on rechromatography over silica gel and elution with a mixture of benzene and ethyl acetate (53) yielded a pure alkaloid (12 mg, Rf, 0.55 in solvent B). The , , , 227 alkaloid crystallised from hexane-ethyl acetate as colourless plates, m.p. 223-25O, UV, (loga, 4-62), 249 (4.06), 283 (3.80) and 292 (3.78) nm; MS, m/e 352 (M+, 100 per cent), 351 (57), 337 (15), 321 (S), 293 (5). 2,Sl (IO), 223 (13), 197 (9), 184 (9), 169 (13), 156 (36). The frûgrnentation pattern and the relative intensities of the ion peaks are reminiscent of a heteroyohimbine particularly of tetrahydroalstonine (ANTONACCIO et al., 1962). Final proof of the identity of alkaloid ASF-4 and tetrahydroalstonine was secured by direct comparison (mixed m.p., Co-TLC).
Pharmacology
The psychopharmacologica1 action of picrinine, the major alkaloid of the flowers of A. scholaris, was studied and it was found to produce moderate to marked sedation in albino mice. It potentiated hexobarbitone narcosis, morphine analgesia and anticonvulsant action of diphenylhydantoin in albino rats. It showed antagonism to amphetamine toxicity and metrazol convulsion in rats. It did not 'selectively antagonise conditioned avoidance response but inhibited both the conditioned (buzzer) as well as unconditioned response (electroshock) in trained rats. The results suggest that the drug is a central nervous system depressant.
Discussion
The flower alkaloids of A. scholaris differ markedly from the major alkaloids of the corresponding barks but are akin to leaf alkaloids. This appears to be the first reported instance of the CO-occurrenceof strictamine (1) and picrinine (II), a fact that can be cired as a circumstantial evidence for the logical surmise that 1 is the immediate precursor of II. The indolenine base, strictamine o r its 16-
......C H 3 1
II
III
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AlkaIoid ASF-4: Chromatography of fraction C over a bed of alumina and elution with benzene
Alkaloids of Alstonia scholaris
89
i i y d r o x y m e t h y l d e r i v a t i v e m i g h t well be the i n t e r m e d i a t e even for the b a r k aIkaloids, echitamidine and e c h i t a m i n e as was adumbrated b y CHATTERJEE and
coworkers (1965). The alkaloids strictamine and p i c r i n i n e e x h i b i t i d e n t i c a l or v e r y close Rr vaIues on thin layer chromatoplates i n a v a r i e t y o f s o i v e n t s y s t e m s and thus a mixture of the a l k a l o i d s shows essentially a s i n g l e spot when s p r a y e d w i t h DRAGENDORFF'S reagent. H o w e v e r , the a l k a l o i d s c a n be d i f f e r e n t i a t e d b y t h e use of CAS r e a g e n t a s s t r i c t a m i n e fails to develop a n y c o l o u r w i t h i t w h i l e p i c r i n i n e g i v e s an orange spot w h i c h changes to pink on k e e p i n g . The method m a y be
The authors are grateful to Professor (Mrs.) A. CHATTERJEE, Department of Chemistry, University College of Science, Calcutta, for samples of picrinine and strictamine and to Professor M. SHAMMA, Pennsylvania State University, U.S.A., for a sample of tetrahydroalstonine. Gratefuithanks are due to Dr. B. C. DAS,I.C.S.N., Gif-sur-Yvette, France, for mass spectral measuremenrs and to Professor O. P. MALHOTRA,Department of Chemistry, B.H.U., for UV, IR and PMR specua.
References
ANTONACCIO, L. D.,PEREIRA,N. A., GILBERT,B., VORBRUEGGEN, H., BUDZIKIEWICZ, H., WILSON, J. M., DURHAM,L. J. and DJERASSI,C.: J. Amer. Chem. Soc. 84, 2161 (1962) CHATTERJEE, A., MUKHERJEE, B., RAY,A. B. and DAS, B.: Tetrahedron Letters 1965, 3633 P. K.: J. Indian Chem. Soc. 46, 635 CHA'ITERJEE,A., MUKHERJEE, B., GHOSAL,S. and BANERJEE, (1969) DJERASSI,C., NAKACAWA, Y., BUDZIKIEWICZ, H., WILSON,J. M., LE MEN, J., POISSON,J. and JANOT,M. M.: Tetrahedron Letters 1962,653 HAMILTON,J. A., HAMOR,T. A., ROBERTSON, J. M. and SIM,G.A.: Proc. Chem. Soc. 1961, 63 HOOKER,J. D.: 'The Flora of British India', L. Reeve & Co., vol. 3, p. 642 (1882) RASTOGI,R. C., KAPIL,R. S. and POPLI,S. P.: Experientia 26, 1056 (1970) A. and GANGULI, G.: J. Org. SCHNOES, H. K., BIEMANN,K., MOKRY,J., KOMPIS,I., CHAT~ERJEE, Chem. 31,1641 (1966) SPITTELER-FRIEDMANN, KASCHNITZ,R., SPITTELER,G., CHAITERJEE, A., ADITYACHOWDHURY, N. and GANGULI, G.: Monatsch. Chem. 95,1228 (1964) , TROJANEK, J., STROUF,O., KAVKOVA,K. and CEKAN,2.: Coll. Czech. Chem. Comin. 25, 2045 (1960) Addresses: Dr. A. B. Ray and MI.S. C . Dutta, Department of Medicinal Chemistry, lnstitute of Medical Sciences, Banaras Hindu University, Varanasi 221005. india Dr. S. K . Bhattacharya, Department of Phaimacology, Institute of Medicat Sciences, Banaras Hindu University, Varanasi 221005, India
Downloaded by: Universite Laval. Copyrighted material.
u s e f u l where the a l k a l o i d s CO-occur i n a p l a n t .
FLOWER ALKALOIDS OF ALSTONlA SCHOLARIS By S . C. DUITA, S. K. BHATTACHARYA and A. B. RAY
Abstract
Alstonia scholaris R. Br. is a large evergreen tree widely cultivated throiighout India. ~ t b e a r scompact, umbellately branched, pubescent cymes of greenish-white fragrant flowers (HOOKER,1882). The bark, leaves and fruits of the plant have been examined and alkaloids, echitamine (HAMILTON et al., 1961), echitamidine (DJERASSI e t al., 1962), picrinine (CHATTERJEE et al., 1965), rhazine (CHATTERJEE et al., 1969) and picralinal (RASTOCIet al., 1970) have been isolated and fully characterised. In an investigation designed t o yield information on the distribution and relationship of alkaloids in A. scholaris, we studied the occurrence of alkaloids in the flowers. T h e pharmacological action of the' major alkaloid, picrinine, has also been studied as a part of Our research program.
Experimental Melting points are uncorrected and were taken on a Toshniwal tneltirig poiiit npparatus in open capillary. Ultraviolet spectra were taken in aldehyde-free ethanol using Cary 14 spectrophotometer. Infrared spectra were recorded in a Perkin Elmer spectrometer mode1 257 in Nujol mull. Proton magnetic resonance (PMR) spectra were determined in deuterochloroform at 60 mHz tising Varian A-60D spectrometer and tetramethylsilane as interna1 standard. Mass spectra were run o n MS 50 instrument. Silica gel used for column chromatography refers to BDH (60-120 mesh). Column chromatography over alumina was performed with neutral grade alumina (Sarabhai M.). TLC plates were prepared with Merck silica gel G and the spots were visualised by sprayitig either ceric ammonium sulphate (CAS) o r DRAGENDORFF'S reagent. Developing solveiits iised were (4) benzeneethyl acetate (5:3) and (B) benzene-chloroform (1:l).
Downloaded by: Universite Laval. Copyrighted material.
The isolation of picrinine, strictamine, tetrahydroalstonine and an uncharacterised indole alkaloid is reported from the flowers of A l s t o n i a s c h o l a r i s . Picrinine, the major alkaloid, bas been found to possess central nervous system depressant action.
Alkaloids of Alstonia scholaris
87
Isolation a n d Characterisation of the Alkaloids Alkaloid ASF-1: Fraction A was dissolved in chloroform and allowed to flow through a drypacked column of alumina ( 1 5 x 4 0 cm). Elution with benzene yielded a base mixture with one major alkaloid which was separated by PLC (developing solvent: 2OIo diethylamine in benzeneethyl acetate = 2:l) and crystallised from hexane-ethyl acetate mixture as colourless needles i-ve). (130 mg), m.p. 100-OlO; RI, 0.23 in solvent A (CAS; -ve, DRACENDORFF: 213 (logs, 4.30), 262 (3.80), Lmi, 238 (3.66) nm, T h e U V spectrum of alkaloid ASF-1, A, indicated the presence of a 3H-indole chromophore and its IR spectrum showed bands for ester carbonyl (1735 cm-'), - C = N (1620 cm'') and aromatic system (1600 cm-'). T h e presence of an ethylidene group (3H doublet a t 6, 1.54 & 1 H quartet at 6, 5.52, J = 7 Hz), a methoxycarbonyl (3H singlet a t 6, 3.72) and 4 vicinal aromatic protons (4H complex multiplet between 6, 7.0-7.8) was revealed frorn its PMR spectrum. T h e mass spectrum of ASF-1 showed the molecular ion. peak a t rnle 322 (100010 abundance) and other significant peaks a t m/e 321 (60), 291 (9), 263 ( 5 9 , 234 (13), 180 (18) and 156 (10). T h e above spectral data are in perfect agreement with those reported for strictamine (1), an indolenine alkaloid (SCHNOESe t al., 1966), isolated from Rhazya strirt'r (SPITTELER-FRIEDMANN et al., 1964) and Vinca minor (TROJANEK et al., 1960). T h e identity of alkaloid ASF-1 with strictamine was established by direct comparison (rnixed m.p., superiinposable IR and Co-TLC) with authentic sample. Alkuloid ASF-2: Chromatography of fraction B over alumina and elution with benzene yielded a gum which showed two DRACENDORFF-staining spots o n a thin layer chromatoplate. T h e major as also the more polar cornponent of this base mixture was separated by PLC (developing solvent: A, CAS +- orange after 5 min) and crystallised from a mixture of hexane-ethyl acetate (9:l) as needles (3 mg), m.p. 225-27O, UV, ,lm,,225, 262 nm, MS, m/e 352 (M+, 93 per cent), 337 (100), 320 (44), 309 ( I l ) , 293 (16), 261 (16), 239 (14), 234 (20), 218 (IO), 207 (14), 206 (15), 194 (14), 181 (22), 180 (26), 168 (22), 154 (12). Insufficient material precluded characterisation of this alkaloid. Alkaloid ASF-3: T h e beiizene-chloroform eluate of the column yielding alkaloid ASF-2 afforded a pure solid (yield, 0.4 g, Rf 0.23 in solvent A, CAS + immediate orange colour changing to pink overnight). I t crystallised from methanol as needles, m.p. 21S0, UV, l.,,, (in EtOH) 237 (loge, 4.08), 287 (3.67) nm, Âmi, 223 (3.98), 260 (3.04);,,,,Â, (in 70010 HCI 104) 239 (3.65), 244 (3.65) and 306 (3.67) nm, MS, rnle 338 (M+, 36 per cent) 320 (50), 279 (20), 261 (26), 239 (100), 234 (24),
Downloaded by: Universite Laval. Copyrighted material.
Extraction of Alkaloids /rom thel Plant Material Flowers of A. sdîo1aris were collected from a big tree within this university campus. T h e material was dried (3.5 kg) under shade, powdered in a waring blender and extracted exhaustively first with petroleurn ether (60-80°) and then with ethanol (9.S0/o) in a continuous extractor. The alcoholic extract was concentrated to a syrup (300 ml) under reduced pressure and stirred mechanically with 7010 aqueous citric acid (1.5 1) for 6 hours. T h e acid-insoluble residue was reinoved by filtration and the-filtrate was shaken with ether ( 3 x 6 0 0 ml) to remove weak bases. T h e cornbined ether e x t r a a was partitioned with 10/o aqueous N a O H to separate phenolic bases, if any, but the alkali extract was found to be free from alkaloids and furnished only veratric acid on acidification. T h e ether layer was washed (H,O)., dried (anhydrous Na,SO,) and evaporated to yield a brown gum (3.2 g), fraction A. T h e aqueous acid left after ether extraction was rendered basic (pH, 8.5) by addition of aminotiium hydroxide and extracted again with ether. T h e ether extract was washed, dried and evaporated to dryness t o give a gummy material (5.6 g), fraction B. T h e petroleum ether e x t r a a of flowers was sirnilarly processed t o furnish a basic gurn (2.5 g), fraction C.
88
Dutta, Bhattacharya and Ray
Planta medica Vol. 30 1976
219 (14)i 218 (15), 206 (ZS), 180 (SO), 170 (27), 169 (31), 154 (37), 140 (D), 136 (26), 130 (30), 115 (30), IR, 1732 (ester carbonyl), 3410 (NH) and 1620 cm*, PMR, 3 H dd at 6, 1.54 (J=8 & 2 Hz) and 1 H m at 6, 5.48 (ethylidene), 3H s at 6, 3.75 (CO,CH,), 1 H broad signal at 6, 5.0 (-O-CH-N-) and 4H m between 6, 6.8-7.6 (ArH). The spectral properties of the alkaloid resembled picrinine (II), the major leaf alkaloid of the plant ( C H A ~ E R Jet E Eal., 1965) and direct comparison (mixed m.p., IR, Co-TLC) of the alkaloid ASF-3 with authentic picrinine established their identity.
furnished a white solid which on rechromatography over silica gel and elution with a mixture of benzene and ethyl acetate (53) yielded a pure alkaloid (12 mg, Rf, 0.55 in solvent B). The , , , 227 alkaloid crystallised from hexane-ethyl acetate as colourless plates, m.p. 223-25O, UV, (loga, 4-62), 249 (4.06), 283 (3.80) and 292 (3.78) nm; MS, m/e 352 (M+, 100 per cent), 351 (57), 337 (15), 321 (S), 293 (5). 2,Sl (IO), 223 (13), 197 (9), 184 (9), 169 (13), 156 (36). The frûgrnentation pattern and the relative intensities of the ion peaks are reminiscent of a heteroyohimbine particularly of tetrahydroalstonine (ANTONACCIO et al., 1962). Final proof of the identity of alkaloid ASF-4 and tetrahydroalstonine was secured by direct comparison (mixed m.p., Co-TLC).
Pharmacology
The psychopharmacologica1 action of picrinine, the major alkaloid of the flowers of A. scholaris, was studied and it was found to produce moderate to marked sedation in albino mice. It potentiated hexobarbitone narcosis, morphine analgesia and anticonvulsant action of diphenylhydantoin in albino rats. It showed antagonism to amphetamine toxicity and metrazol convulsion in rats. It did not 'selectively antagonise conditioned avoidance response but inhibited both the conditioned (buzzer) as well as unconditioned response (electroshock) in trained rats. The results suggest that the drug is a central nervous system depressant.
Discussion
The flower alkaloids of A. scholaris differ markedly from the major alkaloids of the corresponding barks but are akin to leaf alkaloids. This appears to be the first reported instance of the CO-occurrenceof strictamine (1) and picrinine (II), a fact that can be cired as a circumstantial evidence for the logical surmise that 1 is the immediate precursor of II. The indolenine base, strictamine o r its 16-
......C H 3 1
II
III
Downloaded by: Universite Laval. Copyrighted material.
AlkaIoid ASF-4: Chromatography of fraction C over a bed of alumina and elution with benzene
Alkaloids of Alstonia scholaris
89
i i y d r o x y m e t h y l d e r i v a t i v e m i g h t well be the i n t e r m e d i a t e even for the b a r k aIkaloids, echitamidine and e c h i t a m i n e as was adumbrated b y CHATTERJEE and
coworkers (1965). The alkaloids strictamine and p i c r i n i n e e x h i b i t i d e n t i c a l or v e r y close Rr vaIues on thin layer chromatoplates i n a v a r i e t y o f s o i v e n t s y s t e m s and thus a mixture of the a l k a l o i d s shows essentially a s i n g l e spot when s p r a y e d w i t h DRAGENDORFF'S reagent. H o w e v e r , the a l k a l o i d s c a n be d i f f e r e n t i a t e d b y t h e use of CAS r e a g e n t a s s t r i c t a m i n e fails to develop a n y c o l o u r w i t h i t w h i l e p i c r i n i n e g i v e s an orange spot w h i c h changes to pink on k e e p i n g . The method m a y be
The authors are grateful to Professor (Mrs.) A. CHATTERJEE, Department of Chemistry, University College of Science, Calcutta, for samples of picrinine and strictamine and to Professor M. SHAMMA, Pennsylvania State University, U.S.A., for a sample of tetrahydroalstonine. Gratefuithanks are due to Dr. B. C. DAS,I.C.S.N., Gif-sur-Yvette, France, for mass spectral measuremenrs and to Professor O. P. MALHOTRA,Department of Chemistry, B.H.U., for UV, IR and PMR specua.
References
ANTONACCIO, L. D.,PEREIRA,N. A., GILBERT,B., VORBRUEGGEN, H., BUDZIKIEWICZ, H., WILSON, J. M., DURHAM,L. J. and DJERASSI,C.: J. Amer. Chem. Soc. 84, 2161 (1962) CHATTERJEE, A., MUKHERJEE, B., RAY,A. B. and DAS, B.: Tetrahedron Letters 1965, 3633 P. K.: J. Indian Chem. Soc. 46, 635 CHA'ITERJEE,A., MUKHERJEE, B., GHOSAL,S. and BANERJEE, (1969) DJERASSI,C., NAKACAWA, Y., BUDZIKIEWICZ, H., WILSON,J. M., LE MEN, J., POISSON,J. and JANOT,M. M.: Tetrahedron Letters 1962,653 HAMILTON,J. A., HAMOR,T. A., ROBERTSON, J. M. and SIM,G.A.: Proc. Chem. Soc. 1961, 63 HOOKER,J. D.: 'The Flora of British India', L. Reeve & Co., vol. 3, p. 642 (1882) RASTOGI,R. C., KAPIL,R. S. and POPLI,S. P.: Experientia 26, 1056 (1970) A. and GANGULI, G.: J. Org. SCHNOES, H. K., BIEMANN,K., MOKRY,J., KOMPIS,I., CHAT~ERJEE, Chem. 31,1641 (1966) SPITTELER-FRIEDMANN, KASCHNITZ,R., SPITTELER,G., CHAITERJEE, A., ADITYACHOWDHURY, N. and GANGULI, G.: Monatsch. Chem. 95,1228 (1964) , TROJANEK, J., STROUF,O., KAVKOVA,K. and CEKAN,2.: Coll. Czech. Chem. Comin. 25, 2045 (1960) Addresses: Dr. A. B. Ray and MI.S. C . Dutta, Department of Medicinal Chemistry, lnstitute of Medical Sciences, Banaras Hindu University, Varanasi 221005. india Dr. S. K . Bhattacharya, Department of Phaimacology, Institute of Medicat Sciences, Banaras Hindu University, Varanasi 221005, India
Downloaded by: Universite Laval. Copyrighted material.
u s e f u l where the a l k a l o i d s CO-occur i n a p l a n t .
