Epoxy derivatives of aromatic polycyclic hydrocarbons. The synthesis of dibenz[a,c]anthracene 10,11-oxide and its metabolism by rat liver preparations

Abstract

The synthesis of dibenz[a,c]anthracene 10,11-oxide is described. The oxide was unstable and was rapidly decomposed with cold mineral acid into a mixture of 10- and 11- hydroxydibenz[a,c]anthracene. The oxide was converted by rat liver microsomal preparations and homogenates into a product that is probably 10,11-dihydro-10,11-dihydroxydibenz[a,c]anthracene and which was identical with the metabolite formed when dibenz[a,c]anthracene was metabolized by rat liver homogenates. The oxide did not react either chemically or enzymically with GSH. 10,11-Dihydrodibenz[a,c]anthracene and 10,11-dihydrodibenz[a,c]anthracene 12,13-oxide were both metabolized by rat liver preparations into trans-10,11,12,13-tetrahydro-10,11-dihydroxydibenz[a,c] anthracene and the oxide was converted chemically into this dihydroxy compound, and it reacted chemically but not enzymically with GSH. In the alkylation of 4-(p-nitrobenzyl)pyridine, the ;K-region' epoxide, dibenz[a,h]anthracene 5,6-oxide, was more active than either dibenz[a,c]anthracene 10,11-oxide or 10,11-dihydrobenz[a,c]anthracene 12,13-oxide.