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Publicly Available Published by De Gruyter November 19, 2011

Synthesis of lipid A and inner-core lipopolysaccharide (LPS) ligands containing 4-amino-4-deoxy-L-arabinose units

  • Alla Zamyatina , Ralph Hollaus , Markus Blaukopf and Paul Kosma

Attachment of 4-amino-4-deoxy-L-arabinose (Ara4N) to phosphates or sugar hydroxyl groups of lipopolysaccharide (LPS) contributes to bacterial resistance against common antibiotics. For a detailed study of antigenic properties and binding interactions, Ara4N-containing inner-core ligands related to Burkholderia and Proteus LPS have been synthesized in good yields. Glycosylation at position 8 of allyl glycosides of oct-2-ulosonic acids (Ko, Kdo) has been accomplished using an N-phenyltrifluoroacetimidate 4-azido-4-deoxy-L-arabinosyl glycosyl donor followed by azide reduction and global deprotection. The β-L-Ara4N-(1 → 8)-α-Kdo disaccharide was further extended into the branched β-L-Ara4N-(1 → 8)[α-Kdo-(2 → 4)]-α-Kdo trisaccharide via a regioselective glycosylation of a protected triol intermediate. Synthesis of Ara4N-modified lipid A part structure occurring in the LPS of Burkholderia, Pseudomonas, and Klebsiellla strains was accomplished using the H-phosphonate approach. The stereocontrolled assembly of the phosphodiester linkage connecting glycosidic centers of two aminosugars was elaborated employing an anomeric H-phosphonate of cyclic silyl-ether protected 4-azido-4-deoxy-β-L-arabinose, which was coupled to the hemiacetal of the lipid A GlcN-disaccharide backbone. Conditions for global deprotection, which warrant the integrity of “double anomeric” phosphodiester linkage, were successfully developed. Introduction of thiol-terminated spacer at the synthetic ligands allows both coupling to bovine serum albumin (BSA) and immobilization on gold nanoparticles as well as generation of glycoarrays.


European Carbohydrate Symposium (Eurocarb-16), 16th, Sorrento, Italy, 2011-07-03–2011-07-07


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Online erschienen: 2011-11-19
Erschienen im Druck: 2011-11-19

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