Stereoselective thioglycoside syntheses. Part 4. A new approach to 1,4-linked 1-thio-disaccharides and a synthesis of thiomaltose

Abstract

Two approaches are devised for the preparation of thiomaltose (16). Condensation between the sodium salt of 1-thio-α-D-glucopyranose (3) and methyl 2,3,6-tri-O-benzoyl-4-O-trifluoromethylsulphonyl-α-D-galactopyranoside (5) in hexamethylphosphoramide, leads to the methyl α-thiomaltoside derivative (6). On the other hand, the displacement of the C-4 trifluoromethanesulphonate of 1,6-anhydro-D-galactopyranose diacetate (13) by the sodium salt (3) gave the 1,6-anhydro-thio-disaccharide (14). The precursor of (13), 2,3-di-O-acetyl-1,6-anhydro-β-D-galactopyranose (12) was obtained in near quantitative yield from the known 2-O-acetyl-1,6-anhydro-3,4-O-isopropylidene-β-D-galactopyranose (9) by successive hydrolysis of the acetal group, orthoester formation (11), and selective opening of this intermediate through controlled acidic hydrolysis. Acetolysis of the methyl thio-maltoside (8) or the corresponding 1,6-anhydro-thio-disaccharide (14) followed by de-O-acylation afforded 4-S-α-D-glucopyranosyl-4-thio-D-glucopyranose [thiomaltose (16)] in excellent yields. 1,2,3,6-Tetra-O-acetyl-4-S-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)-4-thio-β-D-glucopyranose (15), a useful precursor of thiomaltotriosyloligosaccharides, is also prepared from the acetolysis reaction.