Enantioselectivity of the microsomal epoxide hydrolase-catalyzed hydrolysis of trans-4,5-dimethyl-1,2-epoxycyclohexane

• Published in: Journal of organic chemistry Vol. 50; no. 9; pp. 1471 - 1474
• Main Authors: Bellucci, Giuseppe, Berti, Giancarlo, Ferretti, Maria, Mastrorilli, Ettore, Silvestri, Luca
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01.05.1985
• Subjects: Bioconversions. Hemisynthesis; Biological and medical sciences; Biotechnology; epoxide hydrolase; Fundamental and applied biological sciences. Psychology; hydrolysis; liver; Methods. Procedures. Technologies; microsomes; rabbits; trans-4,5-dimethyl-1,2-epoxycyclohexane; Hydrolysis; Enzymatic synthesis; Stereochemistry; Enantioselectivity; Enzyme; Epoxide hydrolase
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo00209a022

The hydrolysis of the racemic and enantiomeric forms of trans-4,5-dimethyl-1,2-epoxycyclohexane, catalyzed by rabbit liver microsomal epoxide hydrolase (EH), has been investigated to clarify further the mechanism of enantioselection by this enzyme. Both acid-catalyzed and enzymatic hydrolysis yielded exclusively the diol 6 derived from trans diaxial opening of the oxirane ring. Enzymatic hydrolysis of the racemic substrate under saturation conditions was moderately enantioselective, the (-)-epoxide being attacked preferentially to yield the (-)-diol. After 50% conversion an increase in the hydrolysis rate was observed. Incubation of the individual epoxide enantiomers showed that the (+)-(1R,2S,4S,5S)-epoxide is hydrolyzed at a higher rate than its antipode. These results confirm that substrates with 3,4 M helicity of the six-membered ring fit better into the EH active site and prove that the enantioselection must mainly be due to a lower K sub(m) rather than to a higher V sub(max) for the preferentially hydrolyzed enantiomer or conformer.