Improved Synthesis of 2,3,4,6-tetra-О-acetyl-?-D-glucopyranosylhalogenes and 2,3,4,6-tetra-О-acetyl-?,?-D-glucopyranose – Glycosylating Agents of Biologically Active Compounds
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-?-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-?-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 ?,?-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.
1. Schramm S., Dettnerb K., Unverzagta C. Chemical and enzymatic synthesis of buprestin A and B–bitter acylglucosides from Australian jewel beetles (Coleoptera: Buprestidae) // Tetrahedron Letters. 2006. Vol. 47. Р. 7741–7743. DOI: https://doi.org/10.1016/j.tetlet.2006.08.119
2. Huang S., Zhu Y., Pan Y., Wu S. Science Letters: Synthesis of arbutin by two-step reaction from glucose // Journal of Zhejiang University SCIENCE. 2004. Vol. 5 (12). P. 1509–1511.
3. Bundle D. R., Gerken M., Peter T. Synthesis of antigenic determinants of the Brucella a antigen, utilizing methyl 4-azido-4,6-didooxy-?-D-mannopyranoside effi ciently derived from D-mannose // Carbohydrate Research. 1988. Vol. 174. P. 239–251. DOI: https://doi.org/10.1016/0008-62158885094-8
4. Aspinall G. O., Khare N. K., Sood R. K., Chatterjee D., Rivoire B., Brennan P. J. Structure of the glycopeptidolipid antigen of serovar 20 of the Mycobacterium avium serocomplex, synthesis of allyl glycosides of the outer di- and tri-saccharide units of the antigens of serovars 14 and 20, and serology of the derived neoglycoproteins // Carbohydrate Research. 1991. Vol. 216. P. 357–373. DOI: https://doi.org/10.1016/0008-62159284173-P
5. Utkina N. S., Eliseeva G. I., Nikolaev A. V., Shibaev V. N. Fragments of biopolymers containing glycosyl phosphate residues. Russian Journal of Bioorganic Chemistry, 1993, vol. 19, no. 2, pp. 228–235 (in Russian).
6. Cao Z., Qu Y., Zhou J., Liu W., Yao G. Stereoselective Synthesis of Quercetin 3-O-Glycosides of 2-Amino-2- Deoxy-d-Glucose Under Phase Transfer Catalytic Conditions // Journal of Carbohydrate Chemistry. 2015. Vol. 34. P. 28–40.
7. Halen P. K., Murumkar P. R., Giridhar R., Yadav M. R. Prodrug Designing of NSAIDs // Mini-Reviews in Medicinal Chemistry. 2009. Vol. 9. Р. 124–139. DOI: https://doi.org/10.2174/138955709787001695
8. Khan M. S. Y., Khan R. M. Synthesis of the prodrug ibuprofen - D-glucopyranoside and its biological evaluation as a better moiety than the parent drug // Indian Journal of Chemisrty. 2002. Vol. 41B. Р. 1052–1055.
9. Sahu J. K., Kaushik A., Banerjee L. Anti-infl ammatory, analgesic and ulcerogenic activity of ketoprofen glucopyranoside conjugates // International Journal of Pharmaceutical Sciences and Research. 2010. Vol. 1. Р. 96–101.
10. Brito-Arias M. Synthesis and Characterization of Glycosides. 2nd ed. Switzerland : Springer International Publishing, 2016. Chapter 1, 2. DOI: https://doi.org/10.1007/978-3-319-32310-7
11. Vogel A. I. Textbook of Practical Organic Chemistry. 4th ed. L. : Longman, 1987. 1540 p.
12. Jansson K., Noori G., Magnusson G. 2-(Trimethylsilyl) ethyl Glycosides. Transformation into Glycopyranosyl Chlorides // Journal of Organic Chemistry. 1990. Vol. 55. P. 3181–3185. DOI: https://doi.org/10.1021/jo00297a038
13. Eliseeva G. I., Ivanova I. A., Nikolaev A. V., Shibaev V. N. Fragments of biopolymers containing glycosyl phosphate residues. Hydrogen phosphate synthesis of glycosylphosphosugars. Russian Journal of Bioorganic Chemistry, 1991, vol. 17, no. 10, pp. 1401–1411 (in Russian).
14. Zandanel С., Mioskowski C., Baati R., Wagner A. Permethacrylated carbohydrates : synthesis and reactivity in glycosidation reaction // Tetrahedron Letters. 2009. Vol. 65. Р. 9395–9402.
15. Cai T. B., Lu D., Tang X., Zhang Y., Landerholm M., Wang P. G. New Glycosidase Activated Nitric Oxide Donors: Glycose and 3- Morphorlinosydnonimine Conjugates // Journal of Organic Chemistry. 2005. Vol. 70, № 9. Р. 3518–3524. DOI: https://doi.org/10.1021/jo050010o