SYNTHESIS AND ANTIRADICAL ACTIVITY OF CONJUGATES OF URACIL DERIVATIVES WITH AMINO ACIDS

Two synthesis schemes for obtaining new derivatives of 5-hydroxy-1,3,6-trimethyluracil with fragments of protected natural amino acids are proposed. Synthesis includes two ways of ob-taining products - chlorohydride, consisting of the protection of amino acids with phthalic acid and further production of chlorohydrides with their subsequent condensation in methylene chlo-ride with uracil derivative, as well as carbodiimide, with tert-butoxycarbonyl protection of amino acids by amino group, also carried out in methylene chloride in the presence of a water-removing agent N,N'-dicyclohexylcarbodiimide. Both methods of placing protective groups in amino acid molecules are described. New compounds were obtained with yields of 65-98%. Also, by the method of N-alkylation with ethylene chlorohydrin, a linker was introduced into the 6-methyluracil mole-cule with subsequent separation of N1-and N3-derivatives. The reaction was optimized, and the ratio of reagents was revealed, at which the highest yield of the product alkylated at the N3-position is achieved. Successful attempts to attach amino acid fragments to the resulting N3-(2-hydroxy-ethyl)-6-methyluracil during boiling in ethyl alcohol are described. Due to the high biological ac-tivity of all the starting substances, the authors predicted the presence of possible reaction products. The article presents the results of studies of the antiradical (antioxidant) activity of 6-methyluracil derivatives based on the inhibition of the free radical 2,2-diphenylpicrylhydrazine by solutions of specified compounds with different concentrations. It was found that the synthesized conjugates, in particular N3-(2-hydroxyethyl)-6-methyluracil with the amino acid methionine attached via a linker, have increased values of the specified activity in comparison with the initial 6-methyluracil, which makes it possible for their further study. The newly obtained compounds were characterized by the methods of 1H and 13C nuclear magnetic resonance.