CYCLOPENTANE CONSTRUCTION WITH CONTROL OF SIDE-CHAIN CONFIGURATION - ENANTIOSELECTIVE SYNTHESIS OF (+)-BREFELDIN-A

Intramolecular opening of an enantiomerically pure epoxide by an amide enolate (1 --> 2) is shown to be an effective method for cyclopentane construction with control of both ring and side chain absolute configuration. This opening serves as the key step in a synthesis of the Golgi apparatus-blocking macrolide (+)-brefeldin A (3). Other features of the synthesis include improved procedures for the enantioselective hydrogenation of a beta-keto ester to the corresponding beta-hydroxy ester, and for the Julia-Lythgoe reduction of a beta-acetoxy sulfone to the trans alkene.