The epoxidation of 1-hexene (1a) and 2-methyl-1-hexene (1b), two hydrocarbons present in the ambient air as pollutants, is catalyzed by some human and rat P450 enzymes. The enantioselectivities of these processes, when the reactions were carried out using rat and human liver microsomal preparations, were modest and dependent on both P450 composition and substrate concentrations. Various P450 isoforms (rat P450 2B1 and human P450 2C10 and 2A6) catalyzed the double bond oxidation of 1a and 1b with different product enantioselectivities. In the case of 1a, a moderately enantioselective hydroxylation at the allylic C(3) with the formation of 1-hexen-3-ol (4a) by microsomes from control or preinduced rats was also observed. The oxidation of this 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, threo-(+/-)- and erythro-(+/-)-1, 2-epoxyhexan-3-ol, theoretically expected to be formed from 4a, has been investigated.

The stereochemical course of the biotransformation of isoprene by liver enzymes from control and induced rats has been determined. Between the two primarily formed metabolites, 2-methyl-2-vinyloxirane (2) and isopropenyloxirane (3), epoxide 2 is rapidly transformed into the corresponding vicinal racemic diol 4, predominantly through a nonenzymatic hydrolysis reaction. At variance, epoxide 3 is mainly biotransformed into the diol 5 by microsomal epoxide hydrolase (mEH) to give, before 50% conversion, selectively (R)-3-methyl-3-butene-1,2-diol, 5. The hydrolysis competes with the oxidation of the monoepoxide 3 to the corresponding diepoxides 6. Epoxidation of 3 catalyzed by P450 is characterized by a moderate stereoselectivity which, however, was strongly dependent on P450 induction. Treatment of rats with phenobarbital (PB) (an inducer of P450 2B1 and 3A) leads to threo-(2R,2'R)-6 with a high selectivity, while with pyrazole (Pyr) (an inducer of P450 2E1), the formation of both erythro-(2S,2'R)- and threo-(2R,2'R)-6 is favored. The mEH-catalyzed hydrolysis of diepoxides 6 proceeds, although with a moderate turnover rate, with substrate and product diastereo- and enantioselection by nucleophilic attack on the more substituted oxirane ring to give selectively (2R,3S)-3,4-epoxy-2-methyl-1,2-diol (7). Both diols 4 and 5 may be further oxidized on their double bond by P450. These reactions, which occur at a slow rate and are dependent on P450 induction with PB and Pyr, may be negligible in the overall isoprene biotransformation. On the other hand, the epoxydiol 7, which is formed by hydrolysis of diepoxides 6 but it is itself not hydrolyzable, may play an important role in the isoprene toxicity.

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trans-(1-Methyl-2-adamantylidene)-1-methyladamantane (DMAD, 1b) reacts with Br(2) in chlorinated hydrocarbon solvents to give either a bromonium polybromide ion pair or a substitution product, depending on bromine concentration. The first intermediate is a 1:1 pi-complex having K(f) = 1.85(0.19) x 10(3) M(-)(1) at 25 degrees C, which rapidly evolves to the bromonium tribromide ion pair. At high bromine concentration, which shifts all equilibria involving the counteranion of the ion pair intermediate toward the pentabromide species, this bromonium ion is stable and unable to further evolve into products. Temperature-dependent NMR spectra indicate chemical exchange of Br(+) between the sides of the plane containing the two carbons of the bromonium ion. At very low bromine concentration, no ionic intermediate is detected and the reaction rapidly yields a rearranged substitution product, identified as 10. Under these conditions the disappearance of the pi-complex follows a first-order rate law, and the observed rate constant increases with increasing olefin concentration, showing that product formation implies Br(-) as counteranion of the ionic intermediate, whose formation is a reversible process. A comparison of the results reported here for the bromination of 1b with those previously found for the parent olefin, adamantylideneadamantane (1a), shows that steric strain markedly affects the reactivity of the double bond.