| Summary: | 博士 === 靜宜大學 === 應用化學系研究所 === 81 === Nitro-polycyclic aromatic hydrocarbons (nitro-PAHs) are a class of mutagenic environmental pollutants. A number of nitro-PAHs have been found carcinogenic in experimental animals. It has been demonstrated that metabolic activation occurs either via nitro-reduction or ring-oxidation. Thus, it is important to determine the mechanism(s) by which nitro-PAHs initiate cancer.
1-,3- and 6-nitrobenzo[a]pyrene (nitro-BaPs) are nitrated derivatives of the potent carcinogen benzo[a]-pyrene (BaP). In vitro metabolism of 1- and 3-nitro-BaPs has been found to generate multiple pathways for mutagenic activation. The formation of the corresponding trans-7,8-dihydrodiols and 7,8,9,10-tetrahydrotetrols suggests that 1- and 3-nitro-BaP trans-7,8-diol-anti-9,10-epoxides are ultimate metabolitesof the parent nitro-BaPs. Under anaerobic conditions, 1- and 3-nitro-BaPs undergo nitro-reduction to give 1- and 3-amino-BaPs which are potent direct-acting mutagens.
Because only minute amount of metabolites can be obtained via metabolism, it is important to prepare these compounds by organic synthesis. In this thesis, we report the synthesis of the metabolites of 1- and 3-nitro-BaPs, including 1-nitro-BaP trans-7,8-dihydrodiol(1), 1-nitro-BaP trans-7,8-9-10-tetrahydrotetrol (3), 3-nit
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