First Desymmetrization of a Centrosymmetric Molecule in Natural Product Synthesis: Preparation of a Key Fragment in the Synthesis of Hemibrevetoxin B.

Exploitation of molecular symmetry can greatly improve the efficiency of syntheses. The symmetry embedded in the centrosymmetric AB dioxepane fragment of hemibrevetoxin B was exploited for the first time in the preparation of an established intermediate in its total synthesis. Desymmetrization of the centrosymmetric diepoxide 1 by enantioselective epoxide hydrolysis followed by acetonization gave the known synthetic intermediate 2.