紫杉烷类化合物SINENXAN A的化学及结构修饰

【作者】 要芬梅；

【导师】 梁晓天； 郭积玉；

【作者基本信息】 中国协和医科大学 ， 药物化学， 1995， 博士

【摘要】 SIA为我所生物合成法得到的新紫杉烷化合物。为了寻找具有细胞毒性的新型taxol类似物，对SIA进行了结构修饰。本文经过6步反应(SIA→SI—21—5→SIS—09→SIS—12→SIS—26→SIS—45→SIS—53)完成了SIA分子中引入D环oxetane的工作。通过考察每步反应，提出了一条可望高收率得到目的物SIS—53的方法。设计合成了10个母核中引入二氧呋喃环，14β—位或10β—位连有taxol／taxotere侧链的化合物，药理初筛显示一定的细胞毒性。并讨论了这类化合物的构效关系。实验过程中对SIA及其衍生物的性质进行了较详细的号察，总结了反应规律。以S—α—苯乙胺为手性诱导剂完成了taxol侧链的立体选择性合成。本文共合成了86个化合物，其中25个已知物，61个为新紫杉烷化合物。更多还原

【Abstract】 SIA is a new biosynthetic taxane. In order to search for new taxol analogues with cytotoxicity, SIA was studied and modified.A new taxoid with D—ring has been carried out by a reaction sequence of six steps. A more facile synthetic procedure has been put forward by studying and analyzing the features of the reactions involved.A number of new taxoids containing the tetrahydrofuran ring with a exocyclic double bound were esterified at C₁₄ or C₁₀ positions with taxol/taxotere side chain, preliminary pharmacological tests showed that all the compounds have cytotoxicity on KB, HCF8 cmd A2780. Meanwhile, the relationship between their structures and activity was discussed. The side chains of taxol and taxotere were synthesized stere-oselectively. Eighty—six compounds were synthesizd, sixty—one of which are new taxoids.更多还原