天然产物Asperolide A和Asperolide B的合成研究

Asperolides A and B, two representative members of the asperolides family, were first isolated from an endophytic fungus Aspergillus wentii EN-48. The cage-like diterpenoids contain 5/6/6 rings. The natural products and their derivatives were found to have cytotoxic activities against HeLa, HepG2, MCF-7, MDA-MB-231, NCI-H460, SMMC-7721 and SW1990 tumor cell lines, and also have some antibacterial activities. As our continuing efforts in the total syntheses of diterpenoids, we herein wish to launch a research project on the total syntheses of asperolides A and B , to explore common synthetic methods for the construction of this type of cage-like structures. The highlights of our strategy include an asymmetric vinylogous Mukaiyama-Michael reaction, an intramolecular double Michael addition sequence for assembling the fused 5/6/6 ring structure, and an intramolecular aldol reaction for forging the lactone moiety.

Asperolide A和Asperolide B是从名为Aspergillus wentii EN-48的内生真菌中分离得到的两个Asperolide类天然产物，它们含有一个5/6/6并环组成的笼状结构。生物学研究显示，Asperolide类天然产物及衍生物对HeLa、HepG2、MCF-7、MDA-MB-231、NCI-H460、SMM.C-7721和SW1990等多种人类肿瘤细胞活性有一定的抑制作用，其次，它们还有一定的抗菌效果。作为我们在二萜天然产物全合成领域中的后续工作之一，我们拟针对Asperolide A和Asperolide B展开全合成研究，并探索构筑该类天然产物笼状结构的通用方法。主要合成特色包括：（1）不对称插烯Mukaiyama-Michael反应构建手性中心；（2）分子内双Michael反应构建5/6/6并环；（3）分子内aldol反应构建内酯环。