喜树碱的仿生合成:一个四分之一世纪的故事

Biomimetic Synthesis of Camptothecin: A Story of Quarter Century

喜树碱是从中国植物喜树 (Camptothecaacuminata)中分离得到的抗癌生物碱 ,由于其独特的抗癌机理而成为抗癌药研究中的热门课题 .喜树碱属于单萜吲哚生物碱类 ,由色胺和secologanin缩合、衍生而来 .它的仿生合成始于 1972年 ,先后有多人参加 ,直到 1997年在经历了四分之一世纪之后才取得了成功 .介绍喜树碱仿生合成背后鲜为人知的故事 .

Camptothecin is an alkaloid which was isolated in 1966 by Wall and co-workers from Camptotheca acuminata, a tree native to China, and shown to possess unique anticancer properties. Hence, over the subsequent three decades its relatively simple structure has been the objective of many total syntheses using a variety of approaches. Structural features common to camptothecin and vincoside/strictosidine lactams, prompted suggestions as to their biogenetic relationship, which was corroborated by subsequent in vivo incorporation of labelled strictosidine lactam into camptothecin. It thus belongs to the monoterpenoid indole alkaloid family, derived ficin tryptamine and seceologanin, but little is known about the details of its biosynthesis beyond that strictosidine and strictosidine lactam are involved in the biosynthetic process. Once it had been established that the glycosidic lactams were involved in the biogenesis of camptothecin, it seemed an interesting undertaking to transform this fundamental skeleton into camptothecin itself whilst following the postulated biogenetic pathway. The biomimetic synthesis of camptothecin has taken a long time starting in 1972 by Fraser and finishing in 1997 by Liu. This paper discloses the detail of this long story with some previously unreported results.