First total synthesis of the highly potent antitumor lactones 8-chlorogoniodiol and parvistone A: Exploiting a bioinspired late-stage epoxide ring-opening

Abstract

The first protecting group-free total syntheses of the highly potent antitumor chlorinated styryllactone secondary metabolites 8-chlorogoniodiol, parvistone A, and one analogue 8-epi-parvistone A, have been accomplished from commercially available trans-cinnamaldehyde in five steps with high overall yields. The chlorine-bearing stereogenic center of these silent secondary metabolites was introduced via a bioinspired late-stage regioselective epoxide ring-opening strategy. Maruoka asymmetric allylation, acrylation, ring-closing metathesis and asymmetric epoxidation, greatly facilitate the synthesis of the key intermediates goniothalamin oxide and (6S,7S,8S)-isogoniothalamin oxide.