Stereoselective syntheses of a di-, tri-, and tetra-saccharide fragment of Shigella dysenteriae type 1 O-antigen using 3,4,6-tri-O-acetyl-2-azido-2-deoxy-alpha-D-glucopyranosyl chloride as a glycosyl donor.
Methyl 2,4-di-O-benzoyl-alpha-L-rhamnopyranoside (1) furnished a crystalline 3-O-bromoacetyl derivative that was treated with the dichloromethyl methyl ether-ZnCl2 reagent to give 2,4-di-O-benzoyl-3-O-bromoacetyl-alpha-L-rhamnopyranosyl chloride (3). Compounds 1 and 3 were condensed under the conditions of base-deficient, silver trifluoromethanesulfonate-mediated glycosylation to give a fully protected rhamnobioside, which on O-debromoacetylation afforded the disaccharide nucleophile 10. Similar condensation of 3 with methyl 3-O-benzoyl-4,6-O-benzylidene-alpha-D-galactopyranoside, followed by O-debromoacetylation and condensation of the thus formed methyl O-(2,4-di-O-benzoyl-alpha-L-rhamnopyranosyl)-(1----2)-4,6-O-benzylidene- 3-O-benzoyl-alpha-D-galactopyranoside again with 3, gave the trisaccharide glycoside. Subsequent O-debromoacetylation gave 17, having only HO-3(3) unsubstituted. Silver perchlorate-mediated glycosylations of 1, 10, and 17 with 3,4,6-tri-O-acetyl-2-azido-2-deoxy-alpha-D-glucopyranosyl chloride afforded, with high alpha stereoselectivity, protected di-, tri-, and tetra-saccharide glycosides. Subsequent hydrogenation, followed by N-acetylation and O-deacylation, afforded three oligosaccharide glycosides having nonreducing terminal 2-acetamido-2-deoxy-alpha-D-glucopyranosyl residues and comprising successively larger portions of the repeating unit of Shigella dysenteriae type 1 O-antigen.
Pavliak
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National Institutes of Health, Bethesda, MD 20892.
Kovác
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Glaudemans
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D001386:Azides / Q000737:chemistry*; D002240:Carbohydrate Sequence; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000737:chemistry; D006031:Glycosylation; D015335:Molecular Probes; D008969:Molecular Sequence Data; D015394:Molecular Structure; D019081:O Antigens; D009844:Oligosaccharides / Q000138:chemical synthesis*; D011135:Polysaccharides, Bacterial / Q000737:chemistry*; D012762:Shigella dysenteriae / Q000276:immunology*; D014312:Trisaccharides / Q000138:chemical synthesis*
D001386:Azides; D015335:Molecular Probes; D019081:O Antigens; D009844:Oligosaccharides; D011135:Polysaccharides, Bacterial; D014312:Trisaccharides; C070424:1,3,4,6-tetra-O-acetyl 2-azido-2-deoxyglucopyranosylchloride; D003847:Deoxyglucose