Notes Planta Med. 64(1998) 487 Indole Alkaloids from the Trunk Bark of Aspidosperma megalocarpon A.-C. Mitaine1, B. Weniger2, M. Sauvain2, E. Lucumi3, R. Aragón3, and M. ZèchesHanrotl,* 1 Faculté de Pharmacie, Laboratoire de Pharmacognosie, UPRES-A 6013, Reims, France 2 Institut Francais de Recherche Scientifique pour le Développement en Cooperation (ORSTOM), Paris, France 3 Universidad del Valle, Departamento de QuImica, Cali, Colombia Received: December 30, 1997; Revision accepted: January 24, 1998 In the framework of our search for leishmanicidal and antimalarial compounds from Colombian plants, and in con- tinuation of our work on Aspidosperma species (1), we report herein the chemical study of Aspidosperma megalocarpon Mull. Arg. (Apocynaceae). Plants of this genus are used in Colombia against fever and rheumatism (2) and a polar extract of the trunk bark of A. megalocarpon has showed an in vitro antimalarial activity against several Plasmodium species. Our work concerns the isolation of three alkaloids: fendlerine (1), aspidoalbine (2) and aspidolimidine (3) from the trunk bark, which has never been reported thus far. A sample of A. megalocarpon was collected in March 1996 in Bajo Calima; a voucher specimen (BW 031) was deposited in the 1-lerba- rium of the Universidad del Valle (Cali). 15 (÷) fendlerine (1): H, R2 CH2(23)-CH3(24) ' (+) aspidoalbine (2): IS R1 = OCH3, R2 CH2(23)-CH3(24) (+) aspidolimidine (3): R1 H, R2 = CH3(23) Dry ground bark (300 g) was moistened with 10% NH4OH and extracted with CH2CI2. The CH2CI2 extract was purified by a classical acid-base method (1) to give 3.6 g of an alkaloidal mixture (AM) (yield: 1.2 %). AM was fractioned by CC on silica gel (3 x 40 cm) using CH2C12-MeOH (95:5) as the eluent, 10 ml/min. Two main fractions: 1 (0.17 g) (between 200 and 450m1) and II (0.23g) (450—2300ml) were purified by preparative TLC (silica gel; CH2C12-MeOH 99: 1 with NH4OH vapors) to give in the following order of increasing polarity: 1 (in I, 5mg, 0.14% of AM), 2 (in II, 6mg, 0.16%), and 3 (in II, 8mg, 0.22 %). These compounds were identified by comparison of their spectra (UV, IR, MS, NMR) with literature data (3—5). The absolute configurations of 1, 2, and 3 were in agreement with their optical rotation values, respectively being [aiD: + 220° (c 1.2, CHCI3), + 160° (c 0.5, CHCI3), + 244° (c 1, CHCI3). To unequivocally assign protons and carbons of 1, homo- and heteronuclear 2D-NMR spectra (COSY 1H-1H, HMQC, HMBC) were analysed. This also allowed the confirmation of the aromatic substitution in this compound and completed its literature data (5). Fendierine (1): 1H-NMR (300MHz, CDCI3): 5 = 10.75 (IH, 5, OH), 7.05 (IH, d,J = 8,3 Hz, H-9), 6.71 (IH, d,J 8.3 Hz, H-b), 4.15 (1H, t,J = 8.4 Hz, H-18), 4.07 (1H, m, H-18'), 3.90 (1H, dd,J = 11.8, 6.4 Hz, H-2), 3.87 (IH, s, O-CH3), 3.00 (IH, td,J = 8.5, 4.6 Hz, H-5), 2.91 (1 H, m, H-5'), 2.78 (1 H, td,J 11.2, 2.5 Hz, H- 3), 2.63 (IH, m, H-3'), 2.55 (2H, m, CH2-23), 2.10—1.6 (7H, m, H-6, H-17, H-19, H-16, H-16', H-14, H-15), 1.55 (1H, m, H-14'), 1.45 (IH, dt,J = 13.5, 3.5 Hz, H-17'), 1.36 (IH, brd,J = 8.7 Hz, H- 15'), 1.25 (4H, m, H-19', CH3-24); 13C-NMR (75 MHz, CDCI3): S = 172.3 (C-22), 149.0 (C-lI), 137.1 (C-12), 132.4 (C-8), 128.0 (C- 13), 114.5 (C-9), 110.3 (C-iD), 101.7 (C-21), 69.5 (C-2), 65.2 (C- 18), 57.5 (C-7), 56.4 (O-CH3), 48.7 (C-5), 43.7 (C-3), 39.7 (C- 20), 36.4 (C-6), 34.5 (C-19), 32.9 (C-iS), 28.3 (C-23), 26.4 (C- 17), 25.1 (C-16), 21.0 (C-14), 9.8 (C-24)). Information in detail on the work-up procedure and copies of the original spectra are obtainable from the author of correspondence. Acknowledgements The authors are indebted to Lic. Nestor Paz (Universidad del valle) for authentification of the plant material. Victoria Mufloz and Eric Deharo (IBBA-ORSTOM) are also acknowl- edged for testing the antimalarial activity of a polar extract of trunk bark of A. megalocarpon. References Mitaine, A.-C., Mesbah, K., Richard, B., Petermann, C., Arrazola, S., Moretti, C., Zèches-Hanrot, M., Le Men-Olivier, L (1996) Planta Med. 63,458—461. 2 Garcia Barriga, H. (1992) Flora Medicinal de Colombia, Vol. 2, pp. 426—430, Tercer Mundo Editores, Bogota. Gilbert, B., Brissolese, J. A., Wilson, J. M., Budzikiewicz, H., Durham, U., Djerassi, C. (1962) Chem. md. 1949—1950. " Djerassi, C., Antonaccio, L D., Budzikiewicz, H., Wilson, J. M. (1962) Tetrahedron Lett. 1001—1009. Burnell, R. H., Medina, J. D., Ayer, W. A. (1966) Can. J. Chem. 44, 28-31. Prof. M. Zèches-Hanrot Faculté de Pharmacie Laboratoire de Pharmacognosie UPRES-A 6013 Moulin de Ia Housse, Bat. 18 F-51687 Reims cedex 2 France E-mail: monique.zeches@univ-reims.fr Fax: +33-326053596 Planta Medica 64 (1998) 487 © Georg Thieme Verlag Stuttgart• New York 14 IS Downloaded by: Chinese University of Hong Kong. Copyrighted material.