Stereoselective hydrolysis of acyclic olefin oxides to glycols by hepatic microsomal epoxide hydrolase

Abstract

Stereochemistry in the hydrolysis of acyclic olefin oxides by rabbit liver microsomal epoxide hydrolase has been investigated by using cis- and racemic trans-stilbene oxides and racemates of styrene oxide and cis-9,10-epoxystearic acid as model substrates. The model epoxides used were all (except styrene oxide, for which the orientation of the oxirane ring opening was unestablishable) completely hydrolyzed in a stereospecific manner of trans-ring opeining to the corresponding glycols, threo-1,2-diphenyl-1,2-ethanediol from cis-stilbene oxide, meso-1,2-diphenyl-1,2-ethanediol from trans-stilbene oxide, and threo-9,10-dihydroxystearic acid from cis-9,10-epoxystearic acid. The [α] D value of the enzymatically formed threo-diphenylethanediol indicated that the symmetrically cis-substituted oxirane undergoes the introduction of a hydroxyl moiety from water on only one of the oxirane carbons to form the ( R: R)-glycol. Enzymatic hydrolysis of racemates of trans-stilbene oxide and cis-9,10-epoxystearic acid proceeded in an optically selective manner. The (−)- (S:S)- trans-stilbene oxide was hydrolyzed at a faster rate than the (+)- (R:R)- trans-isomer . The racemic cis-9,10-epoxystearic acid yielded an excess of the (+)- threo-dihydroxy acid.