Total synthesis of pyripyropene A

The total synthesis of pyripyropene A, a potent ACAT2 inhibitor with high isozyme selectivity, was completed. Key features of the synthetic strategy include Ti(III)-mediated radical cyclization and Peterson olefination for the construction of the AB ring segment and stereoselective dihydro-γ-pyrone formation (C-ring). The total synthesis provided pyripyropene A in 5.3% overall yield over 17 steps.