Total synthesis of (4 S,10 R)-4-hydroxy-10-methyl-11-oxododec-2-en-1,4-olide and related bioactive marine butenolides

Abstract

Marine-derived microorganisms produce structurally diverse butenolides possessing a variety of bioactivities. Described here is the total synthesis of (4 S,10 R)-4-hydroxy-10-methyl-11-oxododec-2-en-1,4-olide and a related butenolide containing anti stereochemistry at C10–C11. A three-module coupling strategy has been established for synthesis of the stereoisomers of the naturally occurring butenolides by assembling the C3–C7 and C9–C12 fragments via double alkylation of a 1,3-dithiane. The C10–C11 stereochemistry could be easily controlled by an asymmetric aldol condensation, while the butenolide unit was efficiently constructed according to the ring-closing metathesis protocol.