Epoxy derivatives of aromatic polycyclic hydrocarbons. The preparation of benz[a]anthracene 8,9-oxide and 10,11-dihydrobenz[a]anthracene 8,9-oxide and their metabolism by rat liver preparations

Abstract

The syntheses of 10,11-dihydrobenz[a]anthracene 8,9-oxide, benz[a]anthracene 8,9-oxide and 9-hydroxybenz[a]anthracene are described, together with those of a number of related compounds. The epoxides react both chemically and enzymically with water to yield the corresponding dihydrodiols and with reduced glutathione to form glutathione conjugates, and they react chemically with N-acetylcysteine to yield the corresponding mercapturic acids. 8,9-Dihydro-8,9-dihydroxybenz[a]anthracene, formed enzymically from benz[a]anthracene 8,9-oxide, was identical with a dihydrodiol formed when benz[a]anthracene was metabolized by rat liver homogenates. Similarly 10,11-dihydrobenz[a]anthracene 8,9-oxide yielded a dihydrodiol identical with the product formed when 10,11-dihydrobenz[a]anthracene was metabolized.