Stereoselectivity of in vitro isoprene metabolism.

The stereoselectivity of the in vitro conversion of isoprene by liver enzymes of rats and mice was determined. Isoprene was epoxidized by cytochrome P450 of rats and mice to 2-isopropenyloxirane and 2-methyl-2-vinyloxirane with slight but different product enantioselectivity. Only with mouse liver microsomes was a distinct regioselectivity observed. Both monooxiranes were further epoxidized to 2-methyl-2,2'-bioxirane with substrate enantioselectivity, product diastereoselectivity, and with product enantioselectivity. The epoxide hydrolase-catalyzed hydrolysis with rat and mouse liver microsomes occurs with substrate enantioselectivity. A better kinetic resolution was found for 2-isopropenyloxirane than for 2-methyl-2-vinyloxirane. While 2(R)-isopropenyloxirane was conjugated preferentially with glutathione, catalyzed by glutathione S-transferase, no enantiomer differentiation takes place in the case of 2-methyl-2-vinyloxirane.