Synthesis, in Vitro Metabolism, Mutagenicity, and DNA-Adduction of Naphtho[1,2- e ]pyrene

Abstract

Literature data, although limited, underscore the contribution of C 24 H 14 polycyclic aromatic hydrocarbons to the biological activity of the extracts of complex environmental samples. However, little attention has been given to naphthopyrene (NP) isomers due to lack of synthetic standards and, therefore, lack of studies aimed at unequivocal identification of C 24 H 14 isomers in environmental samples. We hypothesize that naphtho [1,2-e] pyrene (N[1,2-e]P), having a fjord region and a bay region might be a potent mutagen. To test our hypothesis, we synthesized N[1,2-e]P by Suzuki reactionand examined its in vitro metabolism with the S9 fraction from phenobarbital/β-naphthoflavone-induced rat liver homogenates. We have tentatively identified its K-region diol as the major metabolite and a fjord region dihydrodiol as minor metabolite. Contrary to our hypothesis, N[1,2-e]P

Synthesis of Dihydrodiol Metabolites of Naphtho[8,1,2- GHI ]Chrysene and Dibenzo[ C,MNO ]Chrysene

“…The Suzuki coupling reaction has proved to be extremely useful in the synthesis of various PAH ring systems (14)(15)(16)(17)(20)(21)(22). This approach is now used widely because it can readily be adopted to a larger scale.…”