SYNTHESIS OF POTENTIALLY CARCINOGENIC HIGHER OXIDIZED METABOLITES OF DIBENZ[A,J]ANTHRACENE AND BENZO[C]CHRYSENE

Bis(dihydrodiols) and other higher oxidized metabolites are implicated as active carcinogenic metabolites of polycyclic aromatic hydrocarbon s, such as dibenz[a,j]anthracene, that possess more than one bay regio n in the molecule. The bis(dihydrodiol) metabolites may potentially un dergo further metabolism to mono- or diepoxides that combine covalentl y with DNA, or undergo conversion to bis(catechols) that enter into a redox cycle with O-2 to form reactive oxygen species that attack DNA. This paper reports convenient syntheses of the terminal ring bis(dihyd rodiol) derivatives of dibenz[a,j]anthracene (5) and benzo[c]chrysene (6) via routes that involve in the key steps double oxidative photocyc lization of tetramethaxy-substituted diolefins. The latter are synthes ized via double Wittig reaction of a bis(phosphonium) salt with 2,3-di methoxybenzaldehyde. Demethylation of the bis(catechol) products follo wed by acetylation and reduction with NaBH4 in the presence of O-2 aff ords the bis(dihydrodiol) products. Several additional higher oxidized derivatives of dibenz[a,j]anthracene, specifically the 3,11-diphenol (14a), the 11-hydroxy-3,4-quinone (15), and the 11-hydroxy-trans-3,4- dihydro diol (2 c), are obtained by an alternative synthesis entailing the re action of the lithium salt of 1,4-dimethoxy-1,4-cyclohexadiene with 1,3-bis(iodoethyl)benzene to furnish a bis-alkylated diketone wh ich undergoes acid-catalyzed cyclization to 3,1 l-diketododecahydrodib enz[a,j]anthracene.