STUDY OF CHEMICAL CARCINOGENESIS .19. SYNTHESIS AND MUTAGENICITY OF 5,11-DIMETHYLCHRYSENE AND SOME METHYL-OXIDIZED DERIVATIVES OF 5-METHYLCHRYSENE

A series of compounds structurally related to the carcinogen and mutagen 5-methylchrysene (1) was synthesized and tested for mutagenicity toward S. typhimurium TA 100. The compounds prepared were 5, 11-dimethylchrysene (2), 5-(hydroxymethyl)chrysene (3), 5-(acetoxymethyl)chrysene (4), 5-carbomethoxychrysene (5), 5-(hydroxymethyl)-l, 2, 3, 4-tetrahydrochrysene (6), 5-carbomethoxy-l, 2, 3, 4-tetrahydrochrysene (7), and 5H-chryseno[4, 5-fccd]pyran-5-one (31). When tested in the presence of rat liver homogenate, 1 and 2 were active while 3-7 were less mutagenic than 1; 31 was highly mutagenic. The mutagenicity of 1 and 2 contrasts with the low activity of 5, 12-dimethylchrysene, which supports the generalization that the structural requirements favoring activity are a hay-region methyl group and a free peri position, both adjacent to an unsubstituted angular ring. The low activity of 3-7 indicates that methyl oxidation is not an important activation process for 1. This agrees with previous studies in which the major proximate mutagen and carcinogen of 1 was identified as l, 2-dihydro-l, 2-dihydroxy-5-methylchrysene. © 1979, American Chemical Society. All rights reserved.