Synthesis of methyl α-d-glucopyranosyl-(1→4)-α-d-galactopyranoside and methyl α-d-xylo-hex-4-ulopyranosyl-(1→4)-α-d-galactopyranoside Original Research Article

The syntheses of methyl α-d-glucopyranosyl-(1→4)-α-d-galactopyranoside (1) and methyl α-d-xylo-hex-4-ulopyranosyl-(1→4)-α-d-galactopyranoside (4) are reported. The keto-disaccharide 4 is of interest in our design, synthesis, and study of pectate lyase inhibitors. The key step in the syntheses was the high-yielding, stereospecific formation of methyl 4,6-O-benzylidene-2′,3′-di-O-benzyl-α-d-glucopyranosyl-(1→4)-2,3,6-tri-O-benzyl-α-d-galactopyranoside (15), which was accomplished by reacting 2,3-di-O-benzyl-4,6-O-benzylidene-d-glucopyranosyl trichloroacetimidate (10) with methyl 2,3,6-tri-O-benzyl-α-d-galactopyranoside (14) in the presence of a catalytic amount of tert-butyldimethylsilyl trifluoromethane sulfonate (TMSOTF). Compound 15 was either hydrogenolyzed to yield disaccharide 1 or treated with NaBH3CN–HCl in 1:1 tetrahydrofuran–ether to yield methyl 2,3,6-tri-O-benzyl-α-d-glucopyranosyl-(1→4)-2,3,6-tri-O-benzyl-α-d-galactopyranoside (2). The free 4′-OH of compound 2 was oxidized to a carbonyl group by a Swern oxidation, and the protecting groups were removed by hydrogenolysis to yield keto-disaccharide 4. These synthetic pathways were simple, yet high yielding.