A CHEMOENZYMATIC APPROACH TO HYDROPEROXYEICOSATETRAENOIC ACIDS - TOTAL SYNTHESIS OF 5(S)-HPETE

A new synthetic approach to enantiomerically pure hydroperoxyeicosatet raenoic acids (HPETEs) is described in which the tetraene skeleton is assembled through chemoselective olefination of a protected hydroperox y aldehyde. Soybean lipoxygenase-mediated dioxygenation of both natura l and unnatural fats produces hydroperoxy dienes in high enantiomeric excess; the observed regioselectivity supports a revised hypothesis fo r substrate specificity. Protection of the diene hydroperoxides as per oxy ketals is followed by regioselective ozonolysis to afford enantiom erically pure 4-peroxy 2,3-enals which undergo olefination to produce peroxytetraenoates. Removal of the monoperoxy ketal and the methyl est er affords enantiomerically pure HPETEs. The generality of the strateg y is illustrated with the first chemical synthesis of 5(S)-HPETE.