Stereoselective synthesis of 3-deoxy-4-S-(1→4)-thiodisaccharides and their inhibitory activities towards β-glycoside hydrolases
The sulfur linkage of β-(1→4)-thiodisaccharides was constructed with excellent diastereoselectivity by Michael addition of 2,3,4,6-tetra-O- acetyl-1-thio-β-D-galactose (2) or its β-D-glucose isomer (3) to sugar-derived (2S, 6S)-6-acetoxymethyl-2-(2-propyloxy)-2H-pyran-3(6H)-one (1). These reactions...
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todo:paper_1434193X_v_n1_p162_Uhrig2023-10-03T16:14:16Z Stereoselective synthesis of 3-deoxy-4-S-(1→4)-thiodisaccharides and their inhibitory activities towards β-glycoside hydrolases Uhrig, M.L. Manzano, V.E. Varela, O. Carbohydrates Enzyme inhibition Glycoside hydrolases Michael addition Thiodisaccharides The sulfur linkage of β-(1→4)-thiodisaccharides was constructed with excellent diastereoselectivity by Michael addition of 2,3,4,6-tetra-O- acetyl-1-thio-β-D-galactose (2) or its β-D-glucose isomer (3) to sugar-derived (2S, 6S)-6-acetoxymethyl-2-(2-propyloxy)-2H-pyran-3(6H)-one (1). These reactions led to the per-O-acetyl glycosides of 3-deoxy-4-S- glycopyranosyl-4-thiohexopyranosid-2-ulose (4 and 5, respectively). Similar conjugated addition to the enone 1 of the isothiouronium salts 6 or 7, precursors in the synthesis of 2 or 3, also afforded the thiodisaccharides 4 or 5, respectively, with exclusive formation of the isomer that has an R configuration for the C-4 stereocenter of the reducing-end. The carbonyl function of 4 and 5 was reduced, and the resulting products were O-deacetylated to give the free 4-S(1→4)-thiodisaccharides 10, 11, 14, and 15, which have a deoxy functionality adjacent to the thio group. These compounds were tested as inhibitors of glycoside hydrolases. Thus 11, the 3-deoxy-4-thiomimetic of Galβ(1→4)Gal, proved to be a competitive inhibitor of the β-galactosidase from E. coli (K i = 0.16 mM). © Wiley-VCH Verlag GmbH & Co. KGaA, 2006. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_1434193X_v_n1_p162_Uhrig |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Carbohydrates Enzyme inhibition Glycoside hydrolases Michael addition Thiodisaccharides |
| spellingShingle |
Carbohydrates Enzyme inhibition Glycoside hydrolases Michael addition Thiodisaccharides Uhrig, M.L. Manzano, V.E. Varela, O. Stereoselective synthesis of 3-deoxy-4-S-(1→4)-thiodisaccharides and their inhibitory activities towards β-glycoside hydrolases |
| topic_facet |
Carbohydrates Enzyme inhibition Glycoside hydrolases Michael addition Thiodisaccharides |
| description |
The sulfur linkage of β-(1→4)-thiodisaccharides was constructed with excellent diastereoselectivity by Michael addition of 2,3,4,6-tetra-O- acetyl-1-thio-β-D-galactose (2) or its β-D-glucose isomer (3) to sugar-derived (2S, 6S)-6-acetoxymethyl-2-(2-propyloxy)-2H-pyran-3(6H)-one (1). These reactions led to the per-O-acetyl glycosides of 3-deoxy-4-S- glycopyranosyl-4-thiohexopyranosid-2-ulose (4 and 5, respectively). Similar conjugated addition to the enone 1 of the isothiouronium salts 6 or 7, precursors in the synthesis of 2 or 3, also afforded the thiodisaccharides 4 or 5, respectively, with exclusive formation of the isomer that has an R configuration for the C-4 stereocenter of the reducing-end. The carbonyl function of 4 and 5 was reduced, and the resulting products were O-deacetylated to give the free 4-S(1→4)-thiodisaccharides 10, 11, 14, and 15, which have a deoxy functionality adjacent to the thio group. These compounds were tested as inhibitors of glycoside hydrolases. Thus 11, the 3-deoxy-4-thiomimetic of Galβ(1→4)Gal, proved to be a competitive inhibitor of the β-galactosidase from E. coli (K i = 0.16 mM). © Wiley-VCH Verlag GmbH & Co. KGaA, 2006. |
| format |
JOUR |
| author |
Uhrig, M.L. Manzano, V.E. Varela, O. |
| author_facet |
Uhrig, M.L. Manzano, V.E. Varela, O. |
| author_sort |
Uhrig, M.L. |
| title |
Stereoselective synthesis of 3-deoxy-4-S-(1→4)-thiodisaccharides and their inhibitory activities towards β-glycoside hydrolases |
| title_short |
Stereoselective synthesis of 3-deoxy-4-S-(1→4)-thiodisaccharides and their inhibitory activities towards β-glycoside hydrolases |
| title_full |
Stereoselective synthesis of 3-deoxy-4-S-(1→4)-thiodisaccharides and their inhibitory activities towards β-glycoside hydrolases |
| title_fullStr |
Stereoselective synthesis of 3-deoxy-4-S-(1→4)-thiodisaccharides and their inhibitory activities towards β-glycoside hydrolases |
| title_full_unstemmed |
Stereoselective synthesis of 3-deoxy-4-S-(1→4)-thiodisaccharides and their inhibitory activities towards β-glycoside hydrolases |
| title_sort |
stereoselective synthesis of 3-deoxy-4-s-(1→4)-thiodisaccharides and their inhibitory activities towards β-glycoside hydrolases |
| url |
http://hdl.handle.net/20.500.12110/paper_1434193X_v_n1_p162_Uhrig |
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| _version_ |
1782030148042752000 |