EFFICIENT NEW SYNTHESES OF POLYCYCLIC AROMATIC HYDROCARBON ORTHO-QUINONES AND THEIR 2′-DEOXYRIBONUCLEOSIDE ADDUCTS

Abstract

Three mechanisms have been proposed to explain the carcinogenic activities of polycyclic aromatic hydrocarbons (PAHs). On the basis of the nature of the active metabolites involved, they may be termed: the diol epoxide mechanism, the quinone mechanism, and the radical-cation mechanism. In connection with studies to evaluate the relative importance of these pathways, we required practical methods for the syntheses of the active PAH metabolites involved. We now report efficient new synthesis of the o-quinones of benzo[a]pyrene (BPQ), 7,12-dimethylbenz[a]anthracene (DMBAQ), and benz[a]anthracene (BAQ). These quinones are convenient synthetic precursors of the related o-catechols, trans-dihydrodiols, and diol epoxides, as well as the stable adducts of the o-quinones with 2-deoxyadenosine and 2′-deoxyguanosine.

Keywords:

• Synthesis of PAH o-quinones
• benzo[a]anthracene
• benzo[a]- pyrene
• 7,12-dimethbenz[a]anthracene
• PAH-deoxyribonucleoside adducts
• Suzuki coupling

Acknowledgments

This investigation was supported by Grant no. CA92537 from the National Cancer Institute.