Stereochemistry of the biotransformation of 1-hexene and 2-methyl-1-hexenewith rat liver microsomes and purified P450s of rats and humans

The epoxidation of 1-hexene (1a) and 2-methyl-1-hexene (1b), two hydrocarbo ns present in the ambient air as: pollutants, is catalyzed by some human an d rat P450 enzymes. The enantioselectivities of these processes, when the r eactions were carried out using rat and human liver microsomal preparations , were modest and dependent on both P450 composition and substrate concentr ations. Various P450 isoforms (rat P450 2B1 and human P450 2C10 and 2A6) ca talyzed the double bond oxidation of 1a and 1b with different product enant ioselectivities. In the case of 1a, a moderately enantioselective hydroxyla tion at the allylic C(3) with the formation of 1-hexen-3-ol (4a) by microso mes from control or preinduced rats was also observed. The oxidation of thi s metabolite was, in turn, catalyzed by rat liver microsomes and mainly by rat P450 2C11, leading exclusively to the formation of 1-hexen-3-one, with no double bond epoxidation being observed. The stereochemical course of the microsomal epoxide hydrolase-catalyzed hydrolysis of the epoxy alcohols, t hreo-(+/-)- and erythro-(+/-)-1,2-epoxyhexan-3-ol, theoretically expected t o be formed from 4a, has been investigated.