Chemical characteristics of the imidazole moiety of deoxyguanosine

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Carcinogens such as arylamines and nitroarens generate mainly C8-arylaminodeoxyguanosine adduct in DNA when they were treated to cells. For the formation of the adduct, a possible mechanism that N7-arylaminodeoxyguanosine is an intermediate was proposed. In order to clear the mechanisms, we used a series of 1-methylbenzimidazole derivatives as models of the imidazole moiety of deoxyguanosine, and intended to synthesize a series of 1-methyl-3-phenylaminobenzimidazoles, the equivalent products of N7-phenylaminodeoxyguanosinium salt. Chemical characteristics of 1-methyl-3-phenylaminobenzimidazoles were also examined. Syntheses of 1-methyl-3-phenylaminobenzimidazoles are as follows. 4-Substituted (CHィイD23ィエD2, H, F, CFィイD23ィエD2, or NOィイD22ィエD2)-2-aminobenzanilide was allowed to react with nitrosobenzene and subsequent removal of the benzoyl group gave 4-substituted-2-phenylazoaniline. This compound was allowed to react with formic acid to give 5-substituted-1-methylbenzimidazoles. Methylation of this compound with MeI proceeded selectively at the N of another side and formed the desired 5-substituted-1-methyl-3-phenylaminobenzimidazolium salts (BI). Heating BI in MeOH/HィイD22ィエD2O produced 5-substituted-1-methyl-2-oxobenzimidazole only in the case of BI with a strongly electron-withdrawing substituent, CFィイD23ィエD2 and NOィイD22ィエD2. alkaline treatment of BI produced 4-substituted-NィイD11ィエD1-methyl-2-phenylazoaniline derivatives in all cases. For comparison between the amino and phenylamino groups, 3-(amino and phenylamino)-1-methyl-5-trifluorobenzimidazoles were used and their reactivity was studied. It was found that phenylamino derivative was more reactive. On the other hand, 7-aminoguanosine is so reactive and formed 2-oxoguanosine so easily. These results suggested that the chemical reactivity of benzimidazole skeleton is quite different from that of benzimidazole.