Enantioselective synthesis of 12-epi-PGF2α and 12,15-diepi-PGF2α

An enantioselective synthesis of 12-epi-PGF(2 alpha), (3) and 12,15-diepi-PGF(2 alpha) (4), PG-like compounds that are probably generated in vivo by nonenzymatic, free-radical-induced peroxidation of arachidonic acid, has been achieved starting from the commercially available Corey lactone (9). The key strategy involves SmI2 reduction of the gamma,delta-epoxy-alpha,beta-unsaturated ester 7, followed by in situ trapping with hexanal; subsequent hydrogenation and decarboxylation affords the stereoselective construction of the lower side chain. This new method is expected to provide a convenient access to various PG-like isoprostanes derived from oxidation of arachidonic acid and cis-4,7,10,13,16,19-docosahexaenoic acid.