SYNTHESIS AND BIOLOGICAL-ACTIVITY OF N-4-METHYL-5-AZACYTIDINES

Protected N-4-methyl and N-4,N-4-dimethyl derivatives of 5-azacytidine 3 and 4 were prepared by selective aminolysis of benzoylated y-1-(bet a-D-ribofuranosyl)-1,3,5-triazin-2(1H)-one 5, by glycosylation of sily lated N-4-methyl- or N-4,N-4-dimethyl-5-azacytosines 7 and 8 with 2,3, 5-tri-O-benzoyl-alpha,beta-D-ribofuranosyl chloride (11) or by several modifications of the isocyanate method. By the isocyanate approach, a lso the alpha-D anomer of protected N-4-methyl-5-azacytidine 17 was ob tained as a minor product. The protected dimethyl derivative 4 was als o obtained by the reaction of isobiuret 22 with dimethylformamide dime thyl acetal. The free nucleosides 1 and 2 were obtained either by amin olysis of the free methoxy nucleoside 23 with methylamine or dimethyla mine, respectively, or by methanolysis or ammonolysis of the correspon ding benzoyl derivatives 3 and 4. The free alpha-D anomer 23 was obtai ned by methanolysis of its tribenzoate 17. Nucleosides 1 and 2 exhibit ed a lower antibacterial, antitumor and antiviral activity than the un substituted 5-azacytidine.