Synthesis of the Angular Ring Tetrahydro Epoxides of the Carcinogens 7- and 12-Methylbenzanthracene and 7,12-Dimethylbenzanthracene

Article abstract of DOI:10.1021/jo00265a025

Tetrahydro epoxide derivatives at the 1,2-and 3,4-positions on the angular ring of carcinogens 7- and 12-methylbenzanthracene (7- and 12-MeBA) and 7,12-dimethylbenzanthracene (7,12-DMBA) have been synthesized in order to probe the basis for the tumorigenicity-enhancing effects of methyl groups on polycyclic aromatic hydrocarbons (PAH).The epoxides were prepared from the corresponding dihydro PAH.For the 7-MeBA and 12-MeBA derivatives, access to the dihydro derivatives was achieved by acetoxylation at the 1- and 4-positions of the tetrahydro ring of 7-and 12-acetoxy-1,2,3,4-tetrahydrobenzanthracene, respectively (Scheme II).For the 7,12-DMBA derivatives, oxidation of 1,2,3,4-tetrahydrobenzanthracene-7,12-quinone afforded the 1- and 4-oxo derivatives, which were converted to the respective dihydro compounds (Scheme III).Alkenes 13 and 22, both of which have a 12-methyl group and C₁-C₂ double bond, were higly susceptible to endoperoxide formation.The dihydro compounds were converted to the epoxides via cyclization of the bromohydrin or bromoacetate derivatives (Scheme IV).The 1,2-bromohydrin and/or bromoacetate derivatives of 3,4-dihydro-12-methylbenzanthracene and 3,4-dihydro-7,12-dimethylbenzanthracene were highly labile and required special handling in order to be purified and converted into the epoxide derivatives.