The formation of dihydrodiols by chemical or enzymic oxidation of 3-methylcholanthrene

Abstract The chemical oxidation of 3-methylcholanthrene in an ascorbic acidferrous sulphate-EDTA reaction mixture gave all five possible dihydrodiols. The structures and stereochemistry of the dihydrodiols were shown by UV, mass and NMR spectral studies and by chemical examination to be cis -2a,3-dihydroxy-3-methylcholanthrene, trans -4,5-dihydro-4,5-dihydroxy-3-methylcholanthrene, trans -7,8-dihydro-7,8-dihydroxy-3-methylcholanthrene, trans -9,10-dihydro-9,10-dihydroxy-3-methylcholanthrene, cis -11,12-dihydro-11,12-dihydroxy-3-methylcholanthrene and trans -11,12-dihydro-11,12-dihydroxy-3-methylcholanthrene. An examination by HPLC of the dihydrodiols formed in the metabolism of 3-methylcholanthrene by rat-liver microsomal preparations showed the presence of trans -4,5-dihydro-4,5-dihydroxy-3-methylcholanthrene, trans -7,8-dihydro-7,8-dihydroxy-3-methylcholanthrene, trans -9,10-dihydro-9,10-dihydroxy-3-methylcholanthrene and trans -11,12-dihydro-11,12-dihydroxy-3-methylcholanthrene, identified by comparison of their UV and chromatographic characteristics with those of authentic standards. Tentative identifications of cis - and trans -1,2-dihydroxy-3-methylcholanthrene, cis -2a,3-dihydroxy-3-methylcholanthrene and cis -11,12-dihydro-11,12-dihydroxy-3-methylcholanthrene as metabolites were made from their mobilities using HPLC. A quantitative comparison of the dihydrodiols formed from 3 H-labelled 3-methylcholanthrene by microsomal preparations from the livers of normal and 3-methylcholanthrene-treated rats was carried out. trans -9,10-Dihydro-9,10-dihydroxy-3-methylcholanthrene and cis - and trans -1,2-dihydroxy-3-methylcholanthrene were formed when 3-methylcholanthrene was incubated with mouse skin in organ culture.