SYNTHESIS OF THE FJORD-REGION CIS-AMINO AND TRANS-AMINO TRIOL DERIVATIVES OF THE CARCINOGENIC HYDROCARBON BENZO[G]CHRYSENE AND UTILIZATION FOR THE SYNTHESIS OF A DEOXYADENOSINE ADDUCT LINKED TO THE N6-AMINO GROUP

Efficient syntheses of the complete set of four diastereomeric fjord-region amino triol derivatives of benzo[g]chrysene in which the amino group in the 14-position and the adjacent 13-hydroxyl group are trans or cis to one another (trans- and cis-5 and 6) is described. This is the first description of the syntheses of the bay- or fjord-region cis-amino triol derivatives of any carcinogenic polycyclic aromatic hydrocarbon(PAH). The amino triols are key synthetic precursors of PAH-oligonucleotide adducts in which the PAH moiety is covalently linked to the exocyclic amino groups of deoxyadenosine or deoxyguanosine. Formation of adducts of this type via reaction of a PAH diol epoxide metabolite with DNA is believed to be a critical step in the mechanism of PAH carcinogenesis. The synthetic amino triol isomers may be used to synthesize PAH-oligonucleotides needed for site-directed mutagenesis studies to relate isomer structural differences to their effects on DNA replication.