A novel regio- and stereocontrolled synthesis of diol epoxide and trans-dihydriol metabolites of polycyclic aromatic hydrocarbons. An application to the synthesis of the bay-region syn- and anti-diol epoxides of the carcinogen 1,4-dimethylphenanthrene

Abstract

Carcinogenic polycyclic aromatic hydrocarbons (PAHs) require metabolic activation in order to exert their tumorigenic activity, typically to the diol epoxides as predicted by the bay-region concept. While a number of synthetic methods toward these diol epoxides are described in the literature, it was felt that a new, entirely different approach may be needed that achieves regio- and stereochemically controlled synthesis of these metabolites, particularly the bay-region analogues. The authors delineate a generally applicable, efficient synthesis of PAH diol epoxides and trans-dihydrodiols and its application to the first synthesis of the putative active metabolites, the bay-region diol epoxides of the carcinogen 1,4-dimethylphenanthrene (1,4-DMPh).