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Spiridonova A. V., Krasnikova N. V., Krasnikov S. V. Improved Synthesis of 2,3,4,6-tetra-О-acetyl-α-D-glucopyranosylhalogenes and 2,3,4,6-tetra-О-acetyl-α,β-D-glucopyranose – Glycosylating Agents of Biologically Active Compounds . Izvestiya of Saratov University. New series. Series: Chemistry. Biology. Ecology, 2020, vol. 20, iss. 2, pp. 131-136. DOI: https://doi.org/10.18500/1816-9775-2020-20-2-131-136


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Improved Synthesis of 2,3,4,6-tetra-О-acetyl-α-D-glucopyranosylhalogenes and 2,3,4,6-tetra-О-acetyl-α,β-D-glucopyranose – Glycosylating Agents of Biologically Active Compounds

Abstract

O,N-Glycosylation reactions are used for the synthesis of prodrugs based on various pharmaceutical substances. This, in turn, can significantly improve their pharmacokinetic and pharmacodynamic parameters, as well as reduce toxic effects. In current study, the objective was to propose new variants of the synthesis of active glycosylating agents, superior to the previously known ones in terms of the use of highly toxic substances, the anomeric composition of the products and the reaction time. In the first case, in order to achieve the result, 1,2,3,4,6-α-D-pentaacetate glucose with high stereoselectivity and yield was brominated in a mixture of acetic acid and methylene chloride with hydrogen bromide, which was obtained separately using the reaction of tetralin and bromine (4 mole of hydrogen bromide per 1 mole of tetralin) and added directly into the reaction mixture. In the second case, 1,2,3,4,6-α-D-pentaacetate glucose with high stereoselectivity and yield was chlorinated on the glycoside atom with a pre-prepared mixture of thionyl chloride and acetic acid, which allowed us to reduce the reaction time by 4 times. In the third case, to prepare α,β-D-tetraacetoglucose, diethylamine was used, which has stronger nucleophilic properties in contrast to the previously used primary amines, so that the reaction proceeded with full conversion 2.5 times faster. The structures and the variants of the obtained compounds are determined by a set of methods of IR, 1H NMR spectroscopy and GC/MS analysis.

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