Biomimetic Synthesis of Cucurbalsaminone A

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 that, we present the first synthesis of cucurbalsaminone A in biomimetic fashion. This synthesis emphasizes key steps including oxidative olefin transposition, Lewis acid-mediated sequential migration of Me and H, and the oxa-di-π-methane rearrangement. This work provides valuable insights into synthesis of complex triterpenoid structures which have potential biological applications.