5-Methylchrysene carcinogenic activity

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 Suzuki cross-coupling reaction is recognized as a novel, abbreviated method for the synthesis of 2-hydroxychrysene, 2-hydroxy-5-methylchrysene, and 8-hydroxy-5-methyl-chrysene from easily accessible reactants (Eq. (8)) [23]. These phenolic compounds constitute precursors for the synthesis of dihydrodiol and bay-region diol epoxide derivatives of chrysene and 5-methylchrysene, which are implicated as the active forms of carcinogenic polynuclear aromatic hydrocarbons. 

In studies on the metabolic activation of 5-MeC (Fig. 9), in vitro metabolism was coupled with mutagenicity and carcinogenicity assays. This work illustrates some techniques which may be used to elucidate structure and determine active metabolites. The metabolic activation of 5-MeC was of interest because of its high carcinogenicity and mutagenicity compared with the other methylchrysene isomers (183). In addition, 5-MeC has two dissimilar bay regions available for formation of bay region dihydrodiol epoxides. 

The pyrolytic oils from municipal solid waste contain substantial concentration of PAH consisting mainly of naphthalene, fluorene and phenanthrene and their alkylated substituents. Some species were of known carcinogenic or mutagenic activity, e.g., methylfluorenes, phenanthrenes, chrysene, and methylchrysene. The PAH were formed via Diels Alder and deoxygenation secondary reactions. Increase in reactor temperature and residence time increased PAH concentration [382]. 

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