Enantioselectivity of the enzymatic hydrolysis of cyclohexene oxide and (±)-1-methylcyclohexene oxide: a comparison between microsomal and cytosolic epoxide hydrolases

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Abstract
The hydrolysis of cyclohexene oxide and (±)-1-methylcyclohexene oxide by rabbit liver microsomal and cytosolic epoxide hydrolyse (mEH and cEH) has been investigated. Microsomal preparations hydrolysed the two epoxides at respective Vs of 17.0 and 3.5 nmol min–1 mg–1 protein, cytosolic preparations at Vs of 0.95 and 1.0 nmol min–1 mg–1 protein. (–)-(R,R)-Cyclohexane-trans-1,2-diol was formed in the mEH and cEH catalysed hydrolysis of cyclohexene oxide with 94% and 22% e.e. respectively. (–)-(R,R)-1-Methylcyclohexene-r-1,t-2-diol, whose absolute configuration was deduced by c.d. measurements of its bis(p-methoxybenzoate), was obtained by partial hydrolysis of (±)-1-methylcylohexene oxide by mEH. The e.e. of the enzymatically formed diol was 94% at 8% conversion and decreased to 56% around 28% conversion. Racemic 1-methylcyclohexane-r-1,t-2-diol was instead obtained in the cEH catalysed hydrolysis of (±)-1-methylcyclohexene oxide. The substrate enantioselectivity of the mEH catalysed hydrolysis of this trisubstituted epoxide is rationalized on the basis of a better stabilization of the transition state for the anti opening at the carbon with (S) configuration of the (1R, 2S)-enantiomer of the epoxide with (3,4 M) helicity, in agreement with the stereochemical course of the analogous reaction of unsubstituted cyclohexene oxide.

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