Divergent Total Synthesis of Four Kopsane Alkaloids: N-Carbomethoxy-10,22-dioxokopsane, Epikopsanol-10-lactam, 10,22-Dioxokopsane, and N-Methylkopsanone.

Abstract

We have achieved the divergent total synthesis of four kopsane alkaloids which share a complex heptacyclic caged ring system. Key transformations include an asymmetric Diels-Alder reaction to assemble the central bicyclo[2.2.2]octane moiety and the quaternary stereocenter at C20, a SmI2 -mediated cascade reduction/aldol reaction to construct the five-membered ring and the quaternary stereocenter at C7, and a late-stage cascade reductive amination/cyclization to establish the highly strained caged ring system.