Synthesis of pentopyranosyl-containing thiodisaccharides. Inhibitory activity against β-glycosidases

Add time:09/07/2019    Source:sciencedirect.com

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).

We also recommend Trading Suppliers and Manufacturers of Methyl 3-deoxy-β-L-erythro-pentopyranoside (cas 19773-91-2). Pls Click Website Link as below: cas 19773-91-2 suppliers

Prev:Synthesis of glycosides of 3-deoxy-4-thiopentopyranosid-2-uloses and their reduction products: 3-deoxy-4-thiopentopyranosides
Next:[43] - Amino Sugars and Amino Cyclitols via Cyclization of Dialdehydes with Nitromethane: 1,4-Diamino-1,4-dideoxy-neo-inositol, Methyl 3-Amino-3-deoxy-β-d-gluco- and β-d-galactopyranoside, and Methyl 3-Amino-3-deoxy-α-d-mannopyranoside Hydrochloride)