Gram-Scale Synthesis of Bufospirostenin A by a Biomimetic Skeletal Rearrangement Approach

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.