Total Synthesis of the Reported Structure of Stresgenin B Enabled by the Diastereoselective Cyanation of an Oxocarbenium

Abstract

We report the first total synthesis of the reported structure of the heat shock protein expression inhibitor stresgenin B. The synthesis features (1) diastereoselective cyanation of an oxocarbenium intermediate en route to the synthetically challenging α-amido dioxolane, (2) Pd-catalyzed hydration of an unstable nitrile, and (3) late-stage Au-catalyzed Meyer-Schuster rearrangement or Ce-mediated Peterson olefination to furnish the exocyclic α,β-unsaturated ester. Our synthetic endeavors allowed us to conclude that the structure of stresgenin B requires revision.