Synthesis of pentopyranosyl-containing thiodisaccharides. Inhibitory activity against β-glycosidases
β-(1→4)-Thiodisaccharides formed by a pentopyranose unit as reducing or non reducing end have been synthesized using a sugar enone derived from a hexose or pentose as Michael acceptor of a 1-thiopentopyranose or 1-thiohexopyranose derivatives. Thus, 2-propyl per-O-acetyl-3-deoxy-4-S-(β-d-Xylp)-4-thi...
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| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_09680896_v17_n17_p6203_Cagnoni |
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todo:paper_09680896_v17_n17_p6203_Cagnoni2023-10-03T15:55:12Z Synthesis of pentopyranosyl-containing thiodisaccharides. Inhibitory activity against β-glycosidases Cagnoni, A.J. Uhrig, M.L. Varela, O. Glycosidase inhibitors Sugar enones Thiodisaccharides Thiopentopyranose 2 propyl per o acetyl 3 deoxy 4 s (beta dextro xylopyranose) 4 thiohexopyranosid 2 ulose benzyl per o acetyl 3 deoxy 4 s (beta dextro galactosylpyranose) 4 thiopentopyranosid 2 ulose beta glucosidase disaccharide thiodisaccharide derivative unclassified drug article concentration response deprotection reaction drug synthesis enzyme inhibitor interaction epimer isomerization reaction analysis structure activity relation beta-Galactosidase beta-Glucosidase Disaccharides Enzyme Inhibitors Stereoisomerism Sulfhydryl Compounds Temperature Escherichia coli β-(1→4)-Thiodisaccharides formed by a pentopyranose unit as reducing or non reducing end have been synthesized using a sugar enone derived from a hexose or pentose as Michael acceptor of a 1-thiopentopyranose or 1-thiohexopyranose derivatives. Thus, 2-propyl per-O-acetyl-3-deoxy-4-S-(β-d-Xylp)-4-thiohexopyranosid-2-ulose (3) and benzyl per-O-acetyl-3-deoxy-4-S-(β-d-Galp)-4-thiopentopyranosid-2-ulose (11) were obtained in almost quantitative yields. The carbonyl function of these uloses was reduced with NaBH4 or K-Selectride, and the stereochemical course of the reduction was highly dependent on the reaction temperature, reducing agent and solvent. Unexpectedly, reduction of 3 with NaBH4-THF at 0 °C gave a 3-deoxy-4-S-(β-d-Xylp)-4-thio-α-d-ribo-hexopyranoside derivative (6) as major product (74% yield), with isomerization of the sulfur-substituted C-4 stereocenter of the pyranone. Reduction of 11 gave always as major product the benzyl 3-deoxy-4-S-(Galp)-4-thio-β-d-threo-pentopyranoside derivative 14, which was the only product isolated (80% yield) in the reduction with K-Selectride in THF at -78 °C. Deprotection of 14 and its epimer at C-2 (13) afforded, respectively the free thiodisaccharides 19 and 18. They displayed strong inhibitory activity against the β-galactosidase from Escherichia coli. Thus, compound 18 proved to be a non-competitive inhibitor of the enzyme (Ki = 0.80 mM), whereas 19 was a mixed-type inhibitor (Ki = 32 μM). © 2009 Elsevier Ltd. All rights reserved. Fil:Cagnoni, A.J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Uhrig, M.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Varela, O. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_09680896_v17_n17_p6203_Cagnoni |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Glycosidase inhibitors Sugar enones Thiodisaccharides Thiopentopyranose 2 propyl per o acetyl 3 deoxy 4 s (beta dextro xylopyranose) 4 thiohexopyranosid 2 ulose benzyl per o acetyl 3 deoxy 4 s (beta dextro galactosylpyranose) 4 thiopentopyranosid 2 ulose beta glucosidase disaccharide thiodisaccharide derivative unclassified drug article concentration response deprotection reaction drug synthesis enzyme inhibitor interaction epimer isomerization reaction analysis structure activity relation beta-Galactosidase beta-Glucosidase Disaccharides Enzyme Inhibitors Stereoisomerism Sulfhydryl Compounds Temperature Escherichia coli |
| spellingShingle |
Glycosidase inhibitors Sugar enones Thiodisaccharides Thiopentopyranose 2 propyl per o acetyl 3 deoxy 4 s (beta dextro xylopyranose) 4 thiohexopyranosid 2 ulose benzyl per o acetyl 3 deoxy 4 s (beta dextro galactosylpyranose) 4 thiopentopyranosid 2 ulose beta glucosidase disaccharide thiodisaccharide derivative unclassified drug article concentration response deprotection reaction drug synthesis enzyme inhibitor interaction epimer isomerization reaction analysis structure activity relation beta-Galactosidase beta-Glucosidase Disaccharides Enzyme Inhibitors Stereoisomerism Sulfhydryl Compounds Temperature Escherichia coli Cagnoni, A.J. Uhrig, M.L. Varela, O. Synthesis of pentopyranosyl-containing thiodisaccharides. Inhibitory activity against β-glycosidases |
| topic_facet |
Glycosidase inhibitors Sugar enones Thiodisaccharides Thiopentopyranose 2 propyl per o acetyl 3 deoxy 4 s (beta dextro xylopyranose) 4 thiohexopyranosid 2 ulose benzyl per o acetyl 3 deoxy 4 s (beta dextro galactosylpyranose) 4 thiopentopyranosid 2 ulose beta glucosidase disaccharide thiodisaccharide derivative unclassified drug article concentration response deprotection reaction drug synthesis enzyme inhibitor interaction epimer isomerization reaction analysis structure activity relation beta-Galactosidase beta-Glucosidase Disaccharides Enzyme Inhibitors Stereoisomerism Sulfhydryl Compounds Temperature Escherichia coli |
| description |
β-(1→4)-Thiodisaccharides formed by a pentopyranose unit as reducing or non reducing end have been synthesized using a sugar enone derived from a hexose or pentose as Michael acceptor of a 1-thiopentopyranose or 1-thiohexopyranose derivatives. Thus, 2-propyl per-O-acetyl-3-deoxy-4-S-(β-d-Xylp)-4-thiohexopyranosid-2-ulose (3) and benzyl per-O-acetyl-3-deoxy-4-S-(β-d-Galp)-4-thiopentopyranosid-2-ulose (11) were obtained in almost quantitative yields. The carbonyl function of these uloses was reduced with NaBH4 or K-Selectride, and the stereochemical course of the reduction was highly dependent on the reaction temperature, reducing agent and solvent. Unexpectedly, reduction of 3 with NaBH4-THF at 0 °C gave a 3-deoxy-4-S-(β-d-Xylp)-4-thio-α-d-ribo-hexopyranoside derivative (6) as major product (74% yield), with isomerization of the sulfur-substituted C-4 stereocenter of the pyranone. Reduction of 11 gave always as major product the benzyl 3-deoxy-4-S-(Galp)-4-thio-β-d-threo-pentopyranoside derivative 14, which was the only product isolated (80% yield) in the reduction with K-Selectride in THF at -78 °C. Deprotection of 14 and its epimer at C-2 (13) afforded, respectively the free thiodisaccharides 19 and 18. They displayed strong inhibitory activity against the β-galactosidase from Escherichia coli. Thus, compound 18 proved to be a non-competitive inhibitor of the enzyme (Ki = 0.80 mM), whereas 19 was a mixed-type inhibitor (Ki = 32 μM). © 2009 Elsevier Ltd. All rights reserved. |
| format |
JOUR |
| author |
Cagnoni, A.J. Uhrig, M.L. Varela, O. |
| author_facet |
Cagnoni, A.J. Uhrig, M.L. Varela, O. |
| author_sort |
Cagnoni, A.J. |
| title |
Synthesis of pentopyranosyl-containing thiodisaccharides. Inhibitory activity against β-glycosidases |
| title_short |
Synthesis of pentopyranosyl-containing thiodisaccharides. Inhibitory activity against β-glycosidases |
| title_full |
Synthesis of pentopyranosyl-containing thiodisaccharides. Inhibitory activity against β-glycosidases |
| title_fullStr |
Synthesis of pentopyranosyl-containing thiodisaccharides. Inhibitory activity against β-glycosidases |
| title_full_unstemmed |
Synthesis of pentopyranosyl-containing thiodisaccharides. Inhibitory activity against β-glycosidases |
| title_sort |
synthesis of pentopyranosyl-containing thiodisaccharides. inhibitory activity against β-glycosidases |
| url |
http://hdl.handle.net/20.500.12110/paper_09680896_v17_n17_p6203_Cagnoni |
| work_keys_str_mv |
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1807321616326066176 |