1. Synthetic mucin fragments: methyl 3-O-(2-acetamido-2-deoxy-beta-D-galactopyranosyl-beta-D- 3-O-(2-acetamido-2-deoxy-3-O-beta-D-galactopyranosyl- beta-D-glucopyranosyl)-beta-D-galactoyranoside. pyranosyl)-beta-D-galactopyranoside
K Kohata, S A Abbas, K L Matta Carbohydr Res. 1984 Sep 1;132(1):127-35. doi: 10.1016/0008-6215(84)85070-3.
Methyl 2,4,6-tri-O-benzyl-beta-D-galactopyranoside (5) was obtained crystalline by way of its 3-O-allyl derivative, which was in turn obtained by ring-opening of a presumed 3,4-O-stannylene derivative of methyl beta-D-galactopyranoside, followed by benzylation. Condensation of 5 with 2-methyl-(2-acetamido-3,4,6-tri-O-acetyl-1,2-dideoxy-beta-D-glucopyra no)-[2,1-d]-2-oxazoline in 1,2-dichloroethane in the presence of p-toluenesulfonic acid afforded the disaccharide derivative methyl 3-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D-glucopyranosyl)-2, 4,6-tri-O-benzyl-beta-D-galactopyranoside (6) Deacetylation of 6 in methanolic sodium methoxide afforded the disaccharide derivative 7, which was acetalated with alpha, alpha-dimethoxytoluene to afford the 4',6'-O-benzylidene acetal (10). Catalytic hydrogenolysis of the benzyl groups of 7 afforded the title disaccharide 8. Glycosylation of 10 with 2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl bromide in 1:1 benzene-nitromethane in the presence of mercuric cyanide gave the fully protected trisaccharide derivative 12. Systematic removal of the protecting groups of 12 then furnished the title trisaccharide 14. The structures of 5, 8, and 14 were all confirmed by 13C-n.m.r. spectroscopy. The 13C-n.m.r. chemical shifts for methyl alpha- and beta-D-galactopyranoside, and also those of their 3-O-allyl derivatives, are recorded, for the sake of comparison, in conjunction with those of compound 5.
2. Synthesis of O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-(1----3)-O-beta-D- galactopyranosyl-(1----4)-2-acetamido-2-deoxy-D-glucopyranose and two related trisaccharides containing the "lacto-N-biose II" unit
R L Thomas, R Dubey, S A Abbas, K L Matta Carbohydr Res. 1987 Nov 15;169:201-12. doi: 10.1016/0008-6215(87)80251-3.
Condensation of 3-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D- glucopyranosyl)-2,4,6-tri-O-acetyl-alpha-D-galactopyranosyl bromide (1) with benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-alpha-D-glucopyranoside in boiling benzene and in the presence of mercuric cyanide afforded a trisaccharide that was O-deacetylated to give benzyl O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-(1----3)-O-beta-D- galactopyranosyl-(1----4)-3,6-di-O-benzyl-2-deoxy-alpha-D-glucopyranosid e, the benzyl groups of which were cleaved by catalytic hydrogenolysis to furnish the title trisaccharide. Alternatively, bromide 1 was allowed to react with 2-acetamido-1,6-anhydro-3-O-benzyl-2-deoxy-beta-D-glucopyranose in 1:1 benzene-nitromethane in the presence of mercuric cyanide, followed by O-deacetylation, column chromatography, and reacetylation to give O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D- glucopyranosyl)-(1----3)-O-(2,4,6-tri-O-acetyl-beta-D-galactopyranosyl)- (1----4)-2-acetamido-1,6-anhydro-3-O-benzyl-2-deoxy-beta-D-glucopyranose . Acetolysis, followed by catalytic hydrogenation and subsequent O-deacetylation furnished the title trisaccharide. A similar condensation of bromide 1 with 4-nitrophenyl 2-acetamido-2-deoxy-4,6-O-(4-methoxybenzylidene)-beta-D-glucopyran oside and 2-nitrophenyl 2-acetamido-2-deoxy-4,6-O-(4-methoxybenzylidene)-alpha-D-galactopy ranoside produced two trisaccharide derivatives, the acetal groups of which were cleaved in hot, 60% aqueous acetic acid, and the resulting diol intermediates O-deacetylated to furnish the desired trisaccharides 4-nitrophenyl O-(2-acetamido-2-deoxy-beta-D- glucopyranosyl)-(1----3)-O-beta-D-galactopyranosyl)-(1----3)-2-acetamido -2- deoxy-beta-D-glucopyranoside and 2-nitrophenyl O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl-(1----3)-O-beta- D-galactopyranosyl-(1----3)-2-acetamido-2-deoxy-beta-D-galactopyranoside .
3. Stereoselective Syntheses of the Conjugation-Ready, Downstream Disaccharide and Phosphorylated Upstream, Branched Trisaccharide Fragments of the O-PS of Vibrio cholerae O139
Sameh E Soliman, Pavol Kováč J Org Chem. 2015 May 15;80(10):4851-60. doi: 10.1021/acs.joc.5b00562. Epub 2015 May 4.
N-Bromosuccinimide-mediated 4,6-O-benzylidene ring opening in 8-azido-3,6-dioxaoctyl 4,6-O-benzylidene-2-deoxy-2-trichloroacetamido-β-D-glucopyranoside afforded the corresponding 4-O-benzoyl-6-bromo-6-deoxy analogue, which was coupled with 3,4,6-tri-O-acetyl-2-O-benzyl-α-D-galactopyranosyl chloride to give the 1,2-cis α-linked disaccharide as the major product. Conventional hydroxyl group manipulation in the latter and products of further conversions gave the desired, functionalized disaccharide α-D-GalpA-(1→3)-β-D-QuipNAc. The rare, foregoing sequence forms the downstream end in the O-specific polysaccharide of both Vibrio cholerae O22 and O139. Halide-assisted glycosylation at 4(I)-OH in 8-azido-3,6-dioxaoctyl 6-O-benzyl-2-deoxy-3-O-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-2-trichloroacetamido-β-D-glucopyranoside, obtained by regioselective reductive opening of the acetal ring in the parent 4(I),6(I)-O-benzylidene derivative, with 2,4-di-O-benzyl-α-colitosyl bromide, gave exclusively the α-linked trisaccharide. The latter was sequentially deacetylated and selectively benzylated to give 8-azido-3,6-dioxaoctyl 2,4-di-O-benzyl-3,6-dideoxy-α-L-xylo-hexopyranosyl-(1→4)-[3-O-benzyl-β-D-galactopyranosyl-(1→3)]-6-O-benzyl-2-deoxy-2-trichloroacetamido-β-D-glucopyranoside. Subsequent selective phosphorylation of the triol, thus obtained, with 2,2,2-trichloroethyl phosphorodichloridate afforded isomeric (R,S)-(P)-4(II),6(II)-cyclic phosphates, which were both obtained in crystalline form and fully characterized. Each of the latter was globally deprotected by catalytic (Pd/C) hydrogenation/hydrogenolysis to give the desired, amino-functionalized, spacer-equipped, phosphorylated upstream trisaccharide fragment of the O-PS of V. cholerae O139.
