Total Synthesis of (−)-Mitrephorone A

The
first synthesis of (−)-mitrephorone A is disclosed along
with discussion and study of synthetic strategies. The natural product
includes a highly congested hexacyclic ent-trachylobane
diterpenoid framework featuring a rare, embedded oxetane. The synthetic
analysis presented dissects a number of approaches for the synthesis
of the central oxetane, including carbonyl-olefin photocycloadditions,
Prins-type cyclizations, and oxidative ring closures. In the successful
route, three [4 + 2] cycloadditions enable rapid construction of all
carbocycles. A novel late-stage oxidative cyclization of a hydroxy
diosphenol with Koser’s reagent furnishes the pivotal oxetane
moiety.