生物活性二倍半萜天然产物Bipolarolide A和Bipolarolide B全合成研究

本项目以具有独特多环笼状结构和显著生物活性的新型萜类天然产物Bipolarolide A和Bipolarolide B为研究对象，重点针对该二倍半萜中具有合成挑战性的“a/b/d/e环系”以及“官能团化桥头全碳季碳中心”的构建，基于本课题组先前在张力桥环体系“桥头烯酮化学及其桥头官能团化”方面的研究，在结合“分子内Coina‒ene环化、氢酰化环化、氢醚化环化、碳骨架后期氧化”等辅助转化的同时，设计了以“钯促进的张力桥环体系环酮氧化脱氢”、“串联邻二醇氧化切断/Aldol缩合”等为主要关键转化的合成策略，以期为该类结构复杂的新型二倍半萜天然产物Bipolarolide A和Bipolarolide B的化学合成提供新思路与新探索。该项目不仅可以丰富相关萜类多环骨架构建研究，同时还将为相关天然产物的生物功能研究提供物质基础。

In this project, structurally complex and new terpenoids having an unprecedented caged polycyclic ring system as well as the biologic significance, Bipolarolide A and Bipolarolide B, are selected as targets for our synthesis design. Focusing on the synthetically challenging construction of the rings a/b/d/e and the functionalized bridgehead quaternary carbon center in these sesterterpenes, a new synthetic strategy featuring the palladium-mediated oxidative dehydrogenation of bridged cyclic ketones and tandem diol oxidative cleavage/Aldol condensation as key transformations is designed on the basis of our previous study on the chemistry of bridgehead enones and its related bridgehead functionalization, wherein the Conia-ene cyclization, hydroacylation, hydroetherification, and the late-stage oxidation of the carbon skeleton are combined tactically. This proposal will establish the development of new design and exploration of total synthesis of these topologically complex sesterterpenes, Bipolarolide A and Bipolarolide B. The present studies not only could enrich the chemistry of constructing the polycyclic skeleton of structurally related terpenes, but also could provide material basis for the biological function research.