Concise Total Synthesis of (−)-Bipolarolide D

• DOI: 10.1021/jacs.4c04059
• Publication Date: 2024-05-08T12:22:26Z
• Authors: Shengling Sun; Qi Wei; Yufei Liu; Zhaohong Lu

Here we report the first and concise total synthesis of a complex ophiobolin-derived sesterterpene, bipolarolide D, which hinges on two strategic applications of pentafulvene: (1) enantioselective pentafulvene-involved [6+2] cycloaddition; (2) regioselective and diastereoselective pentafulvene-involved Heck cyclization. Late-stage selective allylic addition to the ketone moiety facilitates the successful installation of the side chain. This strategy enabled the accomplishment of its first enantioselective total synthesis through a modular approach. This synthesis will facilitate the investigation of relevant biological activities and provide a synthetic blueprint for utilizing fulvenes as versatile synthons in other complex natural product synthesis.