Synthesis of methyl alpha-D-glucopyranosyl-(1 -> 4)-alpha-D-galactopyranoside and methyl alpha-D-xylo-hex-4-ulopyranosyl-(1 -> 4)-alpha-D-galactopyranoside

The syntheses of methyl alpha -D-glucopyranosyl-(1 -->4)-alpha -D-galactopy ranoside (1) and methyl alpha -D-xylo-hex-4-ulopyranosyl- (1 -->4)-alpha -D -galactopyranoside (4) are reported. The keto-disaccharide 4 is of interest in our design, synthesis, and study of pectate lyase inhibitors. The key s tep in the syntheses was the high-yielding, stereospecific formation of met hyl 4,6-O-benzylidene-2 ' ,3 ' -di-O-benzyl-alpha -D-glucopyranosyl-(1 -->4 )-2,3,6-tri-O-benzyl-alpha -D-galactopyranoside (15), which was accomplishe d by reacting 2,3-di-O-benzyl-4,6-O-benzylidene-D-glucopyranosyl trichloroa cetimidate (10) with methyl 2,3,6-tri-O-benzyl-alpha -D-galactopyranoside ( 14) in the presence of a catalytic amount of tert-butyldimethylsilyl triflu oromethane sulfonate (TMSOTF). Compound 15 was either hydrogenolyzed to yie ld disaccharide 1 or treated with NaBH3CN-HCl in 1:1 tetrahydrofuran-ether to yield methyl 2,3,6-tri-O-benzyl-alpha -D-glucopyranosyl-(1 -->4)-2,3,6-t ri-O-benzyl-alpha -D-galactopyranoside (2). The free 4 ' -OH of compound 2 was oxidized to a carbonyl group by a Swern oxidation, and the protecting g roups were removed by hydrogenolysis to yield keto-disaccharide 4. These sy nthetic pathways were simple, yet high yielding. (C) 2001 Elsevier Science Ltd. All rights reserved.