CAS Key Laboratory of Synthetic Chemistry of Natural Substances, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai200032, China.
J Am Chem Soc. 2021 Nov 24;143(46):19576-19586. doi: 10.1021/jacs.1c10067. Epub 2021 Nov 11.
Bufospirostenin A, which was the first spirostanol to be isolated from an animal, possesses an unprecedented 5/7/6/5/5/6 hexacyclic framework. Herein, we report two biomimetic syntheses of this natural product in just seven or nine steps from a readily available steroidal lactone. Key features of the syntheses include a photosantonin rearrangement and a Wagner-Meerwein rearrangement for rapid construction of the rearranged A/B ring system, as well as a cobalt-mediated olefin hydroselenylation and a selenide E2 reaction to accomplish a challenging olefin transposition. Our syntheses provide experimental support for the biogenetic pathway to 5(10→1)-steroids that we have proposed.
Bufospirostenin A 是第一个从动物中分离出来的螺旋甾烷醇，具有前所未有的 5/7/6/5/5/6 六元环骨架。在此，我们报道了两种仿生合成该天然产物的方法，只需从一种易得的甾体内酯出发经过 7 步或 9 步反应即可完成。合成的关键步骤包括光沙桐素重排和 Wagner-Meerwein 重排，用于快速构建重排的 A/B 环系统，以及钴介导的烯烃氢硒化反应和硒化物 E2 反应，以实现具有挑战性的烯烃移位。我们的合成方法为我们提出的 5(10→1)-甾体生物合成途径提供了实验依据。
