4'-Methoxyphenacyl-Assisted Synthesis of β-Kdo Glycosides

Marcelina Mazur (1, 2) , Barbara Barycza (2, 1) , Hanitra Andriamboavonjy (1) , Serge Lavoie (3) , Marielle Tamigney Kenfack (1) , Anaïs Laroussarie (1) , Yves Blériot (1) , Charles Gauthier (4, 3, 1)

1 IC2MP [Poitiers] - Institut de chimie des milieux et matériaux de Poitiers [UMR 7285]
2 Wroclaw University of Environmental and Life Sciences
3 UQAC - Université du Québec à Chicoutimi
4 INRS-IAF - Institut Armand Frappier

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.

Domaines: Sciences du Vivant [q-bio]

Marcelina Mazur, Barbara Barycza, Hanitra Andriamboavonjy, Serge Lavoie, Marielle Tamigney Kenfack, et al.. 4'-Methoxyphenacyl-Assisted Synthesis of β-Kdo Glycosides. Journal of Organic Chemistry, 2016, 81 (22), pp.10585-10599. ⟨10.1021/acs.joc.6b01431⟩. ⟨pasteur-01421190⟩