EFFICIENT SYNTHESES OF THE ANTI-DIOL AND SYN-DIOL EPOXIDE METABOLITES OF THE CARCINOGENIC POLYCYCLIC AROMATIC HYDROCARBON BENZO[G]CHRYSENE

Two new synthetic approaches to the active fjord region anti- and syn-diol epoxide metabolites (3a and 3b) of the potent carcinogenic hydrocarbon benzo[g]chrysene are described. The first of these methods entails initial synthesis of the key intermediate 12-hydroxybenzo[g]chrysene which is transformed in two steps to trans-11,12-dihydroxy-11,12-dihydrobenzo[g]chrysene, 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 benzo[g]chrysene diol epoxides required as starting compounds for the synthesis of specifically alkylated benzo[g]chrysene-oligonucleotide adducts needed for site-directed mutagenesis and other studies to elucidate molecular mechanisms of carcinogenesis.