title: Efficient Iterative Synthesis of O-Acetylated Tri- to Pentadecasaccharides Related to the Lipopolysaccharide of Shigella flexneri Type 3 a through Di- and Trisaccharide Glycosyl Donors.
abstract: Protection against bacterial infections, including shigellosis, can be achieved by antibodies against the bacterial surface polysaccharide. In line with our efforts to develop vaccine candidates for shigellosis, we report herein the synthesis of penta-, deca-, and pentadecasaccharides as well as tri-, octa-, and tridecasaccharides as the endchain and intrachain fragments, respectively, of the surface polysaccharide of Shigella flexneri 3 a, a prevalent serotype. The syntheses relied on the efficiency of the trichloroacetimidate glycosylation chemistry, whereby iteration with di- and trisaccharide building blocks provided fragments made of up to three mono-O-acetylated polysaccharide repeating units. Pd(OH)2-mediated hydrogenation/hydrogenolysis enabled the concomitant removal or conversion of up to 31 protecting groups of 4 different origins to provide the targets as propyl glycosides. Oligosaccharides comprising the octasaccharide segment were shown to display high conformational similarities in solution.
authors.affiliation: Chemistry of Biomolecules, Institut Pasteur, 28 rue du Dr. Roux, 75724, Paris Cedex 15, France.|CNRS UMR 3523, Institut Pasteur, 28 rue du Dr. Roux, 75015, Paris, France.
authors.forename: Zhaoyu
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Chemistry of Biomolecules, Institut Pasteur, 28 rue du Dr. Roux, 75724, Paris Cedex 15, France.|CNRS UMR 3523, Institut Pasteur, 28 rue du Dr. Roux, 75015, Paris, France.|Dextra Laboratories Ltd., Science and Technology Centre, Earley Gate, Reading, RG6 6BZ, U. K.
authors.forename: Aileen F
authors.initials: AF
authors.lastname: Bongat White
authors.affiliation: Chemistry of Biomolecules, Institut Pasteur, 28 rue du Dr. Roux, 75724, Paris Cedex 15, France.|CNRS UMR 3523, Institut Pasteur, 28 rue du Dr. Roux, 75015, Paris, France.
authors.forename: Laurence A
authors.initials: LA
authors.lastname: Mulard
mesh_terms: D000117:Acetylglucosamine / Q000737:chemistry; D002236:Carbohydrate Conformation; D004187:Disaccharides / Q000737:chemistry; D006031:Glycosylation; D006834:Hydrazines / Q000737:chemistry; D008070:Lipopolysaccharides / Q000737:chemistry*; D011134:Polysaccharides / Q000138:chemical synthesis* / Q000737:chemistry; D012763:Shigella flexneri / Q000737:chemistry*; D014312:Trisaccharides / Q000737:chemistry
chemical_list: D004187:Disaccharides; D006834:Hydrazines; D008070:Lipopolysaccharides; D011134:Polysaccharides; D014312:Trisaccharides; C029424:hydrazine; D000117:Acetylglucosamine
keywords: carbohydrates; glycosylation; lipopolysaccharides; protecting groups; vaccines