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

Abstract

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 obtaining products – chlorohydride, consisting of the protection of amino acids with phthalic acid and further production of chlorohydrides with their subsequent condensation in methylene chloride 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 molecule 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-hydroxyethyl)-6-methyluracil during boiling in ethyl alcohol are described. Due to the high biological activity 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. For citation: Khazimullina Yu.Z., Gimadieva A.R. Synthesis and antiradical activity of conjugates of uracil derivatives with amino acids. ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2023. V. 66. N 2. P. 36-44. DOI: 10.6060/ivkkt.20236602.6652.