SYNTHESIS OF DIHYDRODIOLS OF PHENANTHRO[3,4-b]THIOPHENE AND PHENANTHRO[4,3-b]THIOPHENE

Abstract

A number of sulfur analogs of polynuclear aromatic hydrocarbons (thia-PAHs) have been identified in cigarette smoke condensate. Phenanthro[3,4-b]thiophene (P[3,4-b]T) and phenanthro[4,3-b]thiophene (P[4,3-b]T) are sulfur analogs of benzo[c]phenanthrene, which is known to be metabolized to one of the most tumorigenic fjord region diol epoxides tested thus far. Although fjord region diol epoxides of P[3,4-b]T and P[4,3-b]T are expected to be potent mutagens and tumorigens, these two thia-PAHs differ greatly in their mutagenic potencies. In contrast to P[3,4-b]T which is as mutagenic as benzo[a]pyrene, its isoster P[4,3-b]T is a nonmutagenic compound. In order to understand the basis underlying the difference in the mutagenic potency of P[3,4-b]T and P[4,3-b]T, we require these thia-PAHs and their dihydrodiol derivatives for investigating their metabolism and mutagenic/carcinogenic activity. In these studies, we have investigated the Suzuki cross-coupling reaction for an abbreviated synthesis of P[3,4-b]T, P[4,3-b]T, and their dihydrodiol derivatives from easily available reagents.

Keywords:

• metabolites
• phenanthro[3,4-b]thiophene
• phenanthro[4,3-b]-thiophene
• polynuclear sulfur heterocycles
• Suzuki reaction

Acknowledgments

This research was supported by a grant awarded by Philip Morris U.S.A., Inc.