Epoxides carcinogens and biological oxidation

Figure 14.14 Benzenoid aromatic hydrocarbons. Some polycyclic aromatic hydrocarbons (PAHs), such as dibenzo[a,Qpyrene, are carcinogenic. (See "The Chemistry of. . . Epoxides, Carcinogens, and Biological Oxidation" in Section 11.14.)...

Methods for the synthesis of the biologically active dihydrodiol and diol epoxide metabolites of both carcinogenic and noncarcinogenic polycyclic aromatic hydrocarbons are reviewed. Four general synthetic routes to the trans-dihydrodiol precursors of the bay region anti and syn diol epoxide derivatives have been developed. Syntheses of the oxidized metabolites of the following hydrocarbons via these methods are described benzo(a)pyrene, benz(a)anthracene, benzo-(e)pyrene, dibenz(a,h)anthracene, triphenylene, phen-anthrene, anthracene, chrysene, benzo(c)phenanthrene, dibenzo(a,i)pyrene, dibenzo(a,h)pyrene, 7-methyl-benz(a)anthracene, 7,12-dimethylbenz(a)anthracene, 3-methylcholanthrene, 5-methylchrysene, fluoranthene, benzo(b)fluoranthene, benzo(j)fluoranthene, benzo(k)-fluoranthene, and dibenzo(a,e)fluoranthene. 

The stereoselective metabolism of benzo(a)pyrene to an ultimate carcinogen has been well documented, and the metabolic pathway follows the sequence BP BP-7,8-oxide BP-7,8-dihydrodiol BP-7,8-diol-9,10-epoxide (Figure 4.8). The enantioselective toxicities of BP-7,8-dihy-drodiol and BP-7,8-diol-9,10-epoxide have already been discussed, but in order to study the biological effects of (+)- and (—)-benzo(a)pyrene 4,5-oxide, a synthesis of these molecules has been developed based on... 

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