Gram-Scale Synthesis of Bufospirostenin A by a Biomimetic Skeletal Rearrangement Approach
Yu Wang1, Hailong Tian1, Jinghan Gui1
1CAS 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.
Abstract:
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)abeo-steroids that we have proposed.
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