Production of 3', 4'-anhydrovinblastine: a unique chemical synthesis

✍ Scribed by J. Vukovic; A.E. Goodbody; J.P. Kutney; M. Misawa

• Book ID: 104203529
• Publisher: Elsevier Science
• Year: 1988
• Tongue: French
• Weight: 429 KB
• Volume: 44
• Category: Article
• ISSN: 0040-4020
• DOI: 10.1016/s0040-4020(01)85824-5

✦ Synopsis

Preliminary investigations have led to the discovery that ferric ion can couple catharanthine and vindoline, in aqueous acidic media, to produce 3',4'-anhydrovinblastine as the major product. A conversion of 77% couldbe realized under optimized'conditions. Alkaloids derived from plants of the Apocynacae family have long been known for their medicinal properties (1.21. Of these, the Vinca alkaloids vinblastine (VLBl and vincristfne (VCR). isolated from the leaves of Catharanthus roseus, are proven chemotherapeutics in the treatment of various carcinomas (1.3-51. However, these compounds comprise only a minute fraction of the overall alkaloid profile (6.71 thereby complicating isolation and concomitantly, limiting availability of these anti-tumour aqents. Such shortcomings have spurred numerous investigations into possible synthetic routes of production (81. In comparison with the dimerfc products, the Aspidosperma (vindoline) and Iboga (catharanthinel constituents are relatively more plentiful; thus, rather than attemating the more arduous total chemical synthesis, many groups (g-141 have concentrated on the coupling reaction leading to the production of an fntennadiate in VLR and VCR synthesis, 3'.4'-anhydrovinblastlne (AVLBl (15,27,31,34). Most of these processes, although effective, renuire extremes of reaction temperature and initial activation of the Iboga moiety. In