| Abstract
| - Dibenzo[c,p]chrysene (DB[c,p]C) is the only hexacyclic polycyclic aromatic hydrocarbon having twofjord regions, both in different chemical environments. Its environmental presence and relativetumorigenic potency are not known due to the lack of synthetic standards. We report here thesynthesis of dibenzo[c,p]chrysene (1), its proximate carcinogens, i.e., trans-1,2-dihydroxy-1,2-dihydro-DB[c,p]C (2) and trans-11,12-dihydroxy-11,12-dihydro-DB[c,p]C (3), and possible ultimate carcinogens, i.e., anti-trans-1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydro-DB[c,p]C (4) and anti-trans-11,12-dihydroxy-13,14-epoxy-11,12,13,14-tetrahydro-DB[c,p]C (5). The syntheses of 1 and the appropriatelymethoxy-substituted DB[c,p]C (12 and 27), key intermediates for the synthesis of its proximateand ultimate metabolites, were tried first using a Suzuki cross-coupling reaction. However, thecyclization of olefins (10 and 11) gave poor yields of the desired products. An alternate method wasthus developed employing a photochemical approach. The in vitro metabolism of DB[c,p]C wasestablished with the S9 fraction of liver homogenate from phenobarbital/β-naphthoflavone-inducedSprague−Dawley rats. The major dihydrodiol formed was identified as the fjord region 11,12-dihydroxy-11,12-dihydro-DB[c,p]C, while the major and minor phenols were identified as 11-hydroxy-DB[c,p]C and 12-hydroxy-DB[c,p]C, respectively. Further, the DNA adduction studies with the calfthymus DNA led to a mixture of dA and dG adducts for both fjord region diol epoxides (4 and 5).Interestingly, the dA to dG ratio for 1,2-dihydroxy-3,4-epoxide was much higher (3.2) compared tothat of 11,12-dihydroxy-13,14-epoxide (0.5).
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