A click chemistry approach to glycomimetics: Michael addition of 2,3,4,6-tetra-O-acetyl-1-thio-β-d-glucopyranose to 4-deoxy-1,2-O-isopropylidene-l-glycero-pent-4-enopyranos-3-ulose – a convenient route to novel 4-deoxy-(1→5)-5-C-thiodisaccharides

The base catalyzed conjugate Michael addition of the 1-thiosugar, 2,3,4,6-tetra-O-acetyl-β-d-glucopyranose, 1, to a new highly reactive enone 4-deoxy-1,2-O-isopropylidene-l-glycero-pent-4-enopyranos-3-ulose, 2, proceeds steroselectively with formation of adduct 3 in 94% yield. Convenient stereoselective reduction of the C-3 keto function of 3 with L-Selectride® followed by in situ acetylation produces thiodisaccharide 4 in good 82% yield. Cleavage of the 1,2-O-isopropylidene protecting group with p-toluenesulfonic acid in methanol, followed by de-O-acetylation, produced an inseparable anomeric mixture of methyl 4-deoxy-5-C-(β-d-glucopyranosyl)-thio-α/β-l-ribo-pyranoside 5 in 72% overall yield. This approach constitutes a new general two-step click chemistry route to the previously unknown class of 4-deoxy-(1→5)-5-C-thiodisaccharides as stable and biologically important glycomimetics.

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