Synthesis of 5-oxymethyl-1,2,4-triazole-3-carboxamides

Objectives. A key step in the synthesis of natural nucleoside analogs is the formation of a glycosidic bond between the carbohydrate fragment and the heterocyclic base. Glycosylation methods differ in terms of regio- and stereoselectivity. A promising method for the highly specific synthesis of new...

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Main Authors: L. E. Grebenkina, A. N. Prutkov, A. V. Matveev, M. V. Chudinov
Format: Article
Language:Russian
Published: MIREA - Russian Technological University 2022-09-01
Series:Тонкие химические технологии
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Online Access:https://www.finechem-mirea.ru/jour/article/view/1859
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author L. E. Grebenkina
A. N. Prutkov
A. V. Matveev
M. V. Chudinov
author_facet L. E. Grebenkina
A. N. Prutkov
A. V. Matveev
M. V. Chudinov
author_sort L. E. Grebenkina
collection DOAJ
description Objectives. A key step in the synthesis of natural nucleoside analogs is the formation of a glycosidic bond between the carbohydrate fragment and the heterocyclic base. Glycosylation methods differ in terms of regio- and stereoselectivity. A promising method for the highly specific synthesis of new pharmacologically active compounds involves an enzymatic reaction catalyzed by genetically engineered nucleoside phosphorylases. This study is devoted to the synthesis of a library of analogs of nucleoside heterocyclic bases—5-oxymethyl-1,2,4-triazole- 3-carboxamides—in order to investigate the substrate specificity of genetically engineered nucleoside phosphorylases.Methods. A method of cyclization of acylamidrazones obtained from the single synthetic precursor β-N-tert-butyloxycarbonyl-oxalamidrazone was used to parallel-synthesize new 5-alkoxy/ aryloxymethyl-1,2,4-triazole-3-carboxamides. Silica gel column chromatography was used to isolate and purify the synthesized compounds. A complex of physicochemical analysis methods (nuclear magnetic resonance spectroscopy, chromatography, and mass spectrometry) confirmed the structure of the compounds obtained in the work.Results. 5-alkoxy/aryloxymethyl-1,2,4-triazole-3-carboxamides were obtained to study the substrate specificity of genetically engineered nucleoside phosphorylases. The possibility of obtaining new nucleoside analogs by the chemico-enzymatic method was demonstrated on the basis of preliminary assessment results.Conclusions. The physicochemical characteristics of a series of novel 5-alkoxy/aryloxymethyl- 1,2,4-triazole-3-carboxamides were studied along with their potential to act as substrates for the transglycosylation reaction catalyzed by nucleoside phosphorylases.
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spelling doaj-art-5955fd175ddb48e6a88e8459c8296d112025-08-20T02:59:43ZrusMIREA - Russian Technological UniversityТонкие химические технологии2410-65932686-75752022-09-0117431132210.32362/2410-6593-2022-17-4-311-3221686Synthesis of 5-oxymethyl-1,2,4-triazole-3-carboxamidesL. E. Grebenkina0A. N. Prutkov1A. V. Matveev2M. V. Chudinov3MIREA - Russian Technological University (M.V. Lomonosov Institute of Fine Chemical Technologies)MIREA - Russian Technological University (M.V. Lomonosov Institute of Fine Chemical Technologies)MIREA - Russian Technological University (M.V. Lomonosov Institute of Fine Chemical Technologies)MIREA - Russian Technological University (M.V. Lomonosov Institute of Fine Chemical Technologies)Objectives. A key step in the synthesis of natural nucleoside analogs is the formation of a glycosidic bond between the carbohydrate fragment and the heterocyclic base. Glycosylation methods differ in terms of regio- and stereoselectivity. A promising method for the highly specific synthesis of new pharmacologically active compounds involves an enzymatic reaction catalyzed by genetically engineered nucleoside phosphorylases. This study is devoted to the synthesis of a library of analogs of nucleoside heterocyclic bases—5-oxymethyl-1,2,4-triazole- 3-carboxamides—in order to investigate the substrate specificity of genetically engineered nucleoside phosphorylases.Methods. A method of cyclization of acylamidrazones obtained from the single synthetic precursor β-N-tert-butyloxycarbonyl-oxalamidrazone was used to parallel-synthesize new 5-alkoxy/ aryloxymethyl-1,2,4-triazole-3-carboxamides. Silica gel column chromatography was used to isolate and purify the synthesized compounds. A complex of physicochemical analysis methods (nuclear magnetic resonance spectroscopy, chromatography, and mass spectrometry) confirmed the structure of the compounds obtained in the work.Results. 5-alkoxy/aryloxymethyl-1,2,4-triazole-3-carboxamides were obtained to study the substrate specificity of genetically engineered nucleoside phosphorylases. The possibility of obtaining new nucleoside analogs by the chemico-enzymatic method was demonstrated on the basis of preliminary assessment results.Conclusions. The physicochemical characteristics of a series of novel 5-alkoxy/aryloxymethyl- 1,2,4-triazole-3-carboxamides were studied along with their potential to act as substrates for the transglycosylation reaction catalyzed by nucleoside phosphorylases.https://www.finechem-mirea.ru/jour/article/view/1859nucleoside analogs5-oximethyl-1,2,4-triazole-3-carboxamidesparallel synthesisnucleoside phosphorylasesubstrate specificity
spellingShingle L. E. Grebenkina
A. N. Prutkov
A. V. Matveev
M. V. Chudinov
Synthesis of 5-oxymethyl-1,2,4-triazole-3-carboxamides
Тонкие химические технологии
nucleoside analogs
5-oximethyl-1,2,4-triazole-3-carboxamides
parallel synthesis
nucleoside phosphorylase
substrate specificity
title Synthesis of 5-oxymethyl-1,2,4-triazole-3-carboxamides
title_full Synthesis of 5-oxymethyl-1,2,4-triazole-3-carboxamides
title_fullStr Synthesis of 5-oxymethyl-1,2,4-triazole-3-carboxamides
title_full_unstemmed Synthesis of 5-oxymethyl-1,2,4-triazole-3-carboxamides
title_short Synthesis of 5-oxymethyl-1,2,4-triazole-3-carboxamides
title_sort synthesis of 5 oxymethyl 1 2 4 triazole 3 carboxamides
topic nucleoside analogs
5-oximethyl-1,2,4-triazole-3-carboxamides
parallel synthesis
nucleoside phosphorylase
substrate specificity
url https://www.finechem-mirea.ru/jour/article/view/1859
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AT anprutkov synthesisof5oxymethyl124triazole3carboxamides
AT avmatveev synthesisof5oxymethyl124triazole3carboxamides
AT mvchudinov synthesisof5oxymethyl124triazole3carboxamides