The HClO4-catalyzed hydrolysis of (+/-)-2-methyl-5H-dibenzo[a,d]cycloheptene 10,11-oxide, 2, has been investigated by HPLC in THF-water and compared with the microsomal epoxide hydrolase (mEH)-catalyzed hydrolysis. While the former reaction gave the trans and cis diols accompanied by large amounts of 9-formyl-2-methyl-9,10-dihydroanthracene, the enzymatic hydrolysis led only to the trans diol 3. The specific activity of the enzyme towards 2 was 2- to 4.4-fold lower than that towards unsubstituted 5H-dibenzo[a,d]cycloheptene 10,11-oxide, and 150 times lower than that towards cis- stilbene oxide. Both the produced diol and the unreacted epoxide recovered from partial hydrolysis of (+/-)-2 were racemic, showing a complete lack of enantioselection by the enzyme, in contrast with the course of the mEH-promoted hydrolysis of ring monosubstituted cis-stilbene oxides. Epoxide 2, a bad substrate for mEH, behaved as a slow binding inhibitor of mEH, suggesting that the hydrolysis of 2 requires a conformational change in the enzyme-substrate complex.
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