Strategies for the synthesis of brevipolides.

In recent years fifteen 5,6-dihydro-α-pyrone derivatives, bearing either a distinctive cyclopropane or furan ring and named brevipolides A-O (1-15), have been isolated from the invasive plant Hyptis brevipes Poit. Their fascinating structural features, and the potent biological activities, including cytotoxicity against an array of human cancer cell lines and inhibition of the chemokine receptor CCR5, make them attractive synthetic targets. This review article highlights the recent synthetic methodologies and briefly summarizes their biological activities.

Asymmetric synthesis of (-)-brevipolide H through cyclopropanation of the α,ß-unsaturated ketone.

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,ß-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.