Asymmetric total synthesis of ent-Tetrahydrolipstatin from an epoxy alkenol

A highly efficient asymmetric total synthesis of ent-tetrahydrolipstatin (THL) was accomplished from the known epoxy alkenol. The β-lactone portion of THL was synthesized by the epoxide opening with cyanide and stereoselective enolate alkylation method. The side chain was introduced by cross metathesis of the alkene part with 1-decene. Coupling with a protected leucine completed the synthesis of ent-tetrahydrolipstatin.