Structure Elucidation and Enantioselective Total Synthesis of the Potent HMG-CoA Reductase Inhibitor FR901512 via Catalytic Asymmetric Nozaki−Hiyama Reactions

Abstract

The structure elucidation and enantioselective total synthesis of the potent HMG-CoA reductase inhibitor FR901512 were accomplished. FR901512 was prepared in 15 steps from the commercially available 2-bromo-4-methylbenzaldehyde via FR901516 in 16.3% overall yield (89% average yield). The catalytic asymmetric Nozaki−Hiyama reactions developed by us proved their applicability and reliability through this work, enabling the concise, efficient, and protecting-group-free enantioselective total syntheses of these new statins.