Synthesis of glucosamine vinyl ether derivative and its deuterated analog
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Brief Communications Synthesis of glucosamine vinyl ether derivative and its deuterated analog* K. S. Rodygin, V. V. Voronin, and M. S. Ledovskaya St. Petersburg State University, 26 Universitetskii prosp., 198504 St. Petersburg, Russian Federation. E-mail: [email protected] The use of calcium carbide (in the presence of H2O) as a source of acetylene in the reaction with methyl 2-amino-4,6-O-benzylidene-2-deoxy-β-D-glucopyranoside under superbasic conditions (KF, KOH, DMSO, 130 C, 3 h) led to the corresponding vinyl ether in 78% yield. The vinylation does not affect other reaction centers. Replacement of water with deuterium oxide in the reaction mixture gave a stable deuterated analog of this vinyl ether in 72% yield. The one-step isotopic enrichment was practically quantitative (isotopic purity >96%). Introduced deuterium atoms can be used as a convenient label in further transformations. Key words: calcium carbide, vinyl ether, glucosamine, deuterium labeling, vinylation.
Glucosamine is a natural amino sugar that is part of many natural glycoconjugates. In particular, glycosaminoglycans of cartilage tissues contain glucosamine residues. Glucosamine hydrochloride is widely used to treat degenerative diseases of cartilage,1 as well as plays an important role in processes of tissue healing.2,3 Reports on anticancer4,5 and antiinflammatory activity6 of glucosamine and its oligo- and polysaccharide derivatives allow them to be classified as promising multifunctional therapeutic agents. Of particular interest are polymers and glycoproteins with glucosamine residues. About half of all natural proteins are glycosylated and belong to glycoconjugates,7 which are involved in key biological processes.8—15 Introduction * Based on the materials of the XXI Mendeleev Congress on General and Applied Chemistry (September 9—13, 2019, St. Petersburg, Russia).
of deuterium label into the composition of such objects can significantly facilitate identification of intermediates or final products. The problem of synthesis of deuteriumlabeled glycoconjugates can be solved by introducing a vinyl group, including that labeled with deuterium, into carbohydrate molecules with subsequent nucleophilic addition to the double bond of, for example, mercapto groups presented in many peptides. The present work describes a pathway for selective introduction of vinyl and trideuterovinyl group into a glucosamine molecule. Vinylation of carbohydrate molecules with several hydroxy groups leads to the formation of vinyl ethers with several vinyl groups,16,17 the further use of which in the synthesis can lead to complex mixtures of products. Monovinylation requires one free hydroxy group. The remaining hydroxy groups were preliminarily protected according to the procedures described in the
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1401—1404, July, 2020. 1066-5285/20/6907-1401 © 2020 Springer Science+Business Media LLC
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Rodygin et al.
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 7, July, 2020
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