Enantioselectivity of the microsomal epoxide hydrolase: hydrolysis of (±)-cis-3-bromo-1,2-epoxycyclohexane

Abstract

The acid-catalysed and the rabbit microsomal epoxide hydrolyse-catalysed hydrolysis of (±)-cis-3-bromo-1,2-epoxycyclohexane (1) have been investigated. Both reactions were completely regio- and stereo-specific, giving t-3-bromocyclohexane-r-1,t-2-diol (2) as the only product. Epoxide (1) was found to be a much better substrate for the epoxide hydrolyse than its trans-diastereoisomer. Under enzyme saturation conditions the hydrolysis was fairly enantioselective, as shown both by the biphasic shape of its kinetic profile and by the isolation of optically active (–)-(1R,2R,3S)-(1) and (–)(1R,2S,3R)-(2) at incomplete reaction. The absolute configurations have been deduced by correlation with (–)-(R,R)-trans-cyclohexane-1,2-diol. At about 30% conversion, the enantiomeric excesses of unchanged (1) and formed (2) were 24–30% and 56–60%, respectively, and racemic (2) was obtained after complete hydrolysis. The results have been rationalized by a competitive inhibition of (+)-(1S,2S,3R)-(1) on the hydrolysis of (–)-(1) and fit the previously proposed picture describing the substrate enantioselection carried out by the microsomal epoxide hydrolyse.