Kuryanov V. Glucosaminides: synthesis, structure, properties

Dissertation is devoted to development of new approaches of the glycoside bond formation in 2-acetamido-2-deoxy sugars. Research object: 2-acetamido-2-deoxy-D-glucose and its glycosides. The purpose of the study: the development of highly efficient and highly stereoselective method for bulding of O-, S- and N-glycoside bond in the 2-acetamido-2-deoxy sugars, the study of a wide range of properties of the synthesized glucosaminides. Methods: organic synthesis, thin layer chromatography, NMR1H and 13C-H spectroscopy, high performance liquid chromatography, X-ray analysis, biological studies in vitro and in vivo. On the basis of experimental data, it was concluded that the phase transfer catalytic substitution on the anomeric center of a-D-glucosaminyl chloride flows through SN2 reaction. A study of the influence of the nature of N-nucleophiles on the direction of the reaction a-D-glucosaminyl chloride with primary and secondary amines are allowed to offer a mechanism for the formation of O-glucosaminyl hydroxylamine. A simple synthetic method of 1-O-, S- and N-b-derivatives of N-acetyl-D-glucosamine, which allows to obtain different glucosaminides was developed. Several glucosaminides showing significant antibacterial activity against M. luteum and St. aureus, are promising antibacterial drugs. Carbohydrate-amino acid conjugates are promising neurotropici agents, NSAIDs and analgesics. It was proposed a general method for preparing of glycosides of 2-acetamido-2-deoxy-D-glucose, by the crown ethers catalyzed reaction with O-, S-, N-nucleophiles in the "solid base - organic solvent" phase transfer system. As compared with known methods, proposed phase transfer glycosylation except the use of excess of reagent and provides a higher degree of conversion of glycosyl-donor and reduce the role of secondary processes of by-products formation. The proposed approach is easily scalable and allows for industrial of thin organic synthesis and in the synthesis of combinatorial libraries, making the obtained compounds to be available for researches. The differences in the catalytic properties of various crown ethers related to lipophility, dentate and the spatial structure of the macrocycles. It was found that acylhydrazones of formyl phenyl glucosaminides in oxidative cyclization become oxadiazoles, which is an alternative synthetic route to obtaining the corresponding glucosaminides. A study of the influence of the nature of N-nucleophiles in the direction of the reaction glucosaminyloxy succinimide with primary and secondary amines carried out. A simple way to obtaining a per O-acetylated glucosaminyl hydroxylamine was proposed. Spectrum of biological activity of glucosaminides was studied. The effect of structural features on the direction of the biological action was determined.