P. Dussault et Iq. Lee, A CHEMOENZYMATIC APPROACH TO HYDROPEROXYEICOSATETRAENOIC ACIDS - TOTAL SYNTHESIS OF 5(S)-HPETE, Journal of organic chemistry, 60(1), 1995, pp. 218-226
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.