活性天然产物Sinensilactam A和Lycojaponicumin C的全合成

Lycojaponicumin C is a noval alkaloid isolated from Lycopodium japonicum with antitumor activity. Sinensilactam A was isolated from Ganoderma and shows activit yagainst renal fibrosis. Both of these two alkaloids contain [3.3.0] bicyclic ring systems bearing two contiguous stereogenic quaternary carbon atoms at their bridgehead positions. Our group has recently developed a Rh-catalyzed [3+2] cycloaddition reaction to construct the [3.3.0] bicyclic ring systems bearing two contiguous stereogenic quaternary carbon atoms at their bridgehead positions, and we have successfully applied this methodology in the total synthesis of some bioactive natural products. The objective of this project is to develop this Rh-catalyzed [3+2] cycloaddition reaction as a general and efficient synthetic methodology and applied it to the total synthesis of bioactive alkaloids Lycojaponicumin C and Sinensilactam A.

Lycojaponicumin C是从石松中分离得到的一种具有新颖化学结构和抗肿瘤活性的生物碱。Sinensilactam A是从中药灵芝中分离得到的一种新颖的具有抗肾纤维化活性的生物碱。这两种生物碱都含有顺式双桥头季碳的［3.3.0］双环骨架。本课题组近期发展的铑催化［3+2］环化反应可以有效构建具有连续桥头双季碳的并环结构并成功应用于一些活性天然产物的全合成中。本项目的目标是把这个铑催化［3+2］环化反应发展成一个更加高效和通用的合成方法，并应用于活性生物碱Lycojaponicumin C和Sinensilactam A的全合成。

天然产物Sinensilactam A是从灵芝属分离得到的杂萜类次级代谢化合物，其骨架结构新颖，具有多个连续手性中心，其中包含两个连续的全碳季碳中心。本课题组近期发展了一个高效的铑-催化的形式[3+2]环加成反应的方法学来构建含有相邻季碳中心的结构，本项目应用该方法学结合仿生合成策略引入吡咯酮，高效的完成了天然产物Sinensilactam A的全合成。其中合成的关键中间体也是合成Applanatumol类家族分子的先导化合物，为该类家族的全合成提供了思路和依据，并成功合成了天然产物Lingzhilactone B、Applanatumol F和C8’羟基异构体Applanatumol D。