Synthesis of the Dihydrodiol and Diol Epoxide Metabolites of Chrysene and 5-Methylchrysene

Article abstract of DOI:10.1021/jo00359a006

Carcinogenic polycyclic aromatic hydrocarbons are known to undergo enzymatic activation to diol epoxide metabolites bearing an epoxide ring in a bay molecular region.Introduction of a methyl group into a nonbenzo bay region position generally enhances carcinogenic activity.We now report efficient syntheses of the diasteromeric anti and syn bay region diol epoxide derivatives of both chrysene and 5-methylchrysene (5-MC) in both bay regions.The anti- and syn-1,2-diol-3,4-epoxide derivatives of 5-MC (1b and 2b) are the first examples of synthetic diol epoxides with a methyl group in the same bay region as the epoxide ring.NMR analysis indicates that these diol epoxide derivatives and the related dihydrodiols, with the exception of 2b and the syn-7,8-diol-9,10-epoxide of 5-methylchrysene (2c), exist preferentially in the diequational conformation in solution; 2b and 2c show a slight predominance of the diaxial conformer.All the synthetic diol epoxides were sufficiently stable to conduct biological experiments on tumorigenicity and DNA binding on mouse skin; the results confirm that 1b is the major active carcinogenic form of 5-methylchrysene which binds covalently to DNA in vivo.