Regio- and enantio-selectivity of the cytosolic epoxide hydrolase-catalysed hydrolysis of racemic monosubstituted alkyloxiranes

Abstract

The rabbit liver cytosolic epoxide hydrolase-catalysed hydrolysis of racemic octyloxirane 1a, butyloxirane 1b, neopentyloxirane 1c and t-butyloxirane 1d to the corresponding ethane-1,2-diol derivatives was investigated and the regio- and enantio-selectivity of this reaction was determined for the first time. Attack by water always occurred at the primary carbon, with an (R) substrate enantioselection that was highly dependent on the branching of the alkyl chain and was the highest for compound 1d. The results show a striking analogy with those found with the microsomal enzyme and suggest similar mechanisms and chiral discrimination abilities for the two epoxide hydrolases.