Biomimetic Synthesis of Cucurbalsaminone A

Abstract

Cucurbalsaminones, notable for their unique 5/6/3/6/5-fused pentacyclic triterpenoid structure, are potent inhibitors of P-glycoprotein. In this study, we propose a biosynthetic pathway starting from lanosterol, aiming to elucidate how these types of complex structures are synthesized by nature. Based on this, we present the first synthesis of cucurbalsaminone A in a biomimetic fashion. This synthesis emphasizes key steps including allylic oxidation/olefin isomerization, Lewis acid-mediated sequential migration of Me and H, and the oxa-di-π-methane rearrangement.

Topics & Concepts