Efficient Syntheses of the anti- and syn-Diol Epoxide Metabolites of the Carcinogenic Polycyclic Aromatic Hydrocarbon Benzochrysene

Article abstract of DOI:10.1021/jo00124a026

Two new synthetic approaches to the active fjord region anti- and syn-diol epoxide metabolites (3a and 3b) of the potent carcinogenic hydrocarbon benzochrysene are described.The first of these methods entails initial synthesis of the key intermediate 12-hydroxybenzochrysene which is transformed in two steps to trans-11,12-dihydroxy-11,12-dihydrobenzochrysene, the synthetic precursor of 3a and 3b.The second method involves in the key step oxidative photocyclization of a 1,2-diarylethylene having methoxy groups at appropriate sites for subsequent conversion to the dihydrodiol function.These methods allow efficient preparative scale synthesis of the benzochrysene diol epoxides required as starting compounds for the synthesis of specifically alkylated benzochrysene-oligonucleotide adducts needed for site-directed mutagenesis and other studies to elucidate molecular mechanisms of carcinogenesis.