Asymmetric Synthesis of (−)-Brevipolide H through Cyclopropanation of the α,β-Unsaturated Ketone

Abstract

Brevipolides are 5,6-dihydro-γ-pyrone derivatives, first reported in 2004 as the inhibitors of the chemokine receptor CCR5 and exhibiting cytotoxicity against cancer cells. Starting from the C2 symmetric diene-diol 2, ent-brevipolide H was synthesized for the first time in 11 steps. The anti-addition of the sulfur ylide to the α,β-unsaturated enones was developed to give the key cyclopropane moiety. The synthetic (-)-brevipolide H showed an IC50 value of 7.7 μM against PC-3 cells.