Efficient syntheses of the active metabolites of carcinogenic polycyclic aromatic hydrocarbons

Carcinogenic polycyclic aromatic hydrocarbons (PAHs) require metabolic activation to exert their deleterious effects. Three pathways of activation have been proposed. The first entails initial formation of traps-dihydrodiol metabolites that undergo conversion to highly mutagenic diol epoxides that interact with DNA to form covalent adducts. The second path involves formation of PAH radical cations that react with DNA to form unstable depurinating adducts. In the third path, the trans-dihydrodiols are converted by aldo-keto reductase enzymes to reactive and redox-active o-quinones capable of interacting with DNA to form both stable and depurinating adducts. Investigations of the relative importance of these mechanisms require methods for the synthesis of the active metabolites involved. We now report efficient new syntheses of the o-quinones of benzo[a]pyrene (BPQ), 7,12-dimethyl-benz[a]anthracene (DMBAQ), and bent[a]anthracene (BAQ), convenient synthetic precursors of the corresponding trans-dihydrodiols, diol epoxides, and catechols. (C) 2004 American Chemical Society.