4'-Methoxyphenacyl-Assisted Synthesis of β-Kdo Glycosides.
3-Deoxy-β-d-manno-oct-2-ulosonic acid (β-Kdo) glycosides are mainly found in capsular polysaccharides and extracellular exopolysaccharides from Gram-negative bacteria. These compounds have profound biological implications in immune response and act as virulence factors. We have developed a novel methodology for the stereoselective synthesis of β-Kdo glycosides via the use of a 4'-methoxyphenacyl (Phen) auxiliary group at the C1 position of a peracetylated β-Kdo thioglycoside. Under the promotion of NIS/AgOTf in acetonitrile, a series of Kdo glycosides was synthesized in good yield and β-selectivity while minimizing the formation of undesirable glycals. Stereoselectivity of the glycosylation was shown to be modulated by various factors such as promotor, solvent, anomeric ratio of donor, nature of acceptor, and Phen substitution. Chemoselective cleavage of the Phen group was performed under the action of Zn/HOAc. DFT calculations together with experimental results suggested that α-triflate and a six-membered α-spiroPhen are plausible intermediates of the reaction, accounting for the enhanced formation of β-Kdo glycosides. The developed methodology could be applied to the synthesis of β-Kdo-containing glycans from pathogenic bacteria.
Institut de Chimie IC2MP, CNRS-UMR 7285, Équipe Synthèse Organique, Université de Poitiers , 4 rue Michel Brunet, 86073 Poitiers Cedex 9, France.|Department of Chemistry, Wroclaw University of Environmental and Life Sciences , Norwida 25, 50-375 Wroclaw, Poland.
Marcelina
M
Mazur
Institut de Chimie IC2MP, CNRS-UMR 7285, Équipe Synthèse Organique, Université de Poitiers , 4 rue Michel Brunet, 86073 Poitiers Cedex 9, France.|Department of Chemistry, Wroclaw University of Environmental and Life Sciences , Norwida 25, 50-375 Wroclaw, Poland.
Barbara
B
Barycza
Institut de Chimie IC2MP, CNRS-UMR 7285, Équipe Synthèse Organique, Université de Poitiers , 4 rue Michel Brunet, 86073 Poitiers Cedex 9, France.
Hanitra
H
Andriamboavonjy
Laboratoire LASEVE, Département des Sciences Fondamentales, Université du Québec à Chicoutimi , 555 boul. de l'Université, Chicoutimi (Québec), Canada G7H 2B1.
Serge
S
Lavoie
Institut de Chimie IC2MP, CNRS-UMR 7285, Équipe Synthèse Organique, Université de Poitiers , 4 rue Michel Brunet, 86073 Poitiers Cedex 9, France.
Marielle
M
Tamigney Kenfack
Institut de Chimie IC2MP, CNRS-UMR 7285, Équipe Synthèse Organique, Université de Poitiers , 4 rue Michel Brunet, 86073 Poitiers Cedex 9, France.
Anaïs
A
Laroussarie
Institut de Chimie IC2MP, CNRS-UMR 7285, Équipe Synthèse Organique, Université de Poitiers , 4 rue Michel Brunet, 86073 Poitiers Cedex 9, France.
Yves
Y
Blériot
Institut de Chimie IC2MP, CNRS-UMR 7285, Équipe Synthèse Organique, Université de Poitiers , 4 rue Michel Brunet, 86073 Poitiers Cedex 9, France.|Laboratoire LASEVE, Département des Sciences Fondamentales, Université du Québec à Chicoutimi , 555 boul. de l'Université, Chicoutimi (Québec), Canada G7H 2B1.|INRS-Institut Armand-Frappier, Université du Québec , 531 boul. des Prairies, Laval (Québec), Canada H7V 1B7.
Charles
C
Gauthier
D066241:Carbon-13 Magnetic Resonance Spectroscopy; D006027:Glycosides / Q000138:chemical synthesis*; D006031:Glycosylation; D011134:Polysaccharides / Q000737:chemistry; D066244:Proton Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization
D006027:Glycosides; D011134:Polysaccharides