An expedient modeling construction of the BCDEF pentacyclic ring system analog of aconitine and racemulosine

Abstract

In this study, we report an expedient strategy for the construction of a highly bridged model pentacyclic framework resembling the BCDEF ring system of aconitine and racemulosine. Key transformations include a transannular palladium-catalyzed α-vinylation to forge the bicyclo[3.2.1]octane BF ring system, a retro-Mannich/Mannich process to install the requisite C17 amino group with correct stereochemistry, and a silver-catalyzed Conia-ene cyclization to assemble the piperidine E ring. The developed methodology enabled the efficient synthesis of the BEF tricyclic core and, subsequently, the functionalized BCDEF pentacyclic framework. This work establishes a viable synthetic pathway toward the modeled core framework of aconitine-type alkaloids and lays a solid foundation for future total synthesis studies.