Kinetics and stereochemistry of the microsomal epoxide hydrolase-catalyzed hydrolysis of cis-stilbene oxides

✍ Scribed by Giuseppe Bellucci; Dr. Cinzia Chiappe; Giovanni Ingrosso

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 586 KB
• Volume: 6
• Category: Article
• ISSN: 0899-0042
• DOI: 10.1002/chir.530060711

✦ Synopsis

The microsomal epoxide hydrolase (mEH)-catalyzed hydrolysis of cis-4,4'-dimethylstilbene oxide (la), cis4,4'-diethylstilbene oxide (lb), cis-4,I'-diisopropylstilbene oxide (lc), and cis-4,4'-dichlorostilbene oxide (Id) have been investigated using rabbit liver microsomal preparations. The kinetic parameters, K , and V,,, and the absolute stereochemistry of the reactions have been determined and compared with those of cisstilbene oxide (le). All epoxides l a 4 are hydrolyzed by mEH with high product enantioselectivity to give (R,R)-(+)-diols with ee 3 90%. The presence of the substituents on the phenyl rings markedly reduces the rates of mEH catalyzed hydrolysis with respect to cis-stilbene oxide, by increasing K , and reducing V,, in the cases of la, lb, and Id, or reducing only the V, , in the case of lc. The very low V,,,, together with a persistent ability to fit into the mEH active site, make all these epoxides, and particularly lc, inhibitors of cis-stilbene oxide hydrolysis. The kinetic and stereochemical results are interpreted on the basis of the proposed topology of the mEH active site. o 1994 wiley-Liss, Inc.