Synthesis of a common trisaccharide fragment of glycoforms of the outer core region of the Pseudomonas aeruginosa lipopolysaccharide

The first synthesis of the common trisaccharide of glycoforms of the outer core region of the Pseudomonas aeruginosa lipopolysaccharide is reported. A fully protected trisaccharide precursor was prepared via a highly efficient α-(1→4)-glucosylation of a β-(1→3)-linked 6-O-benzyl-2-azido-2-deoxy-3-O-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)-α-d-galactopyranoside. In contrast, an alternative sequence of glycosylations, which involves β-glucosylation of an α-(1→4)-linked Glc-GalN3 unit, did not lead to the target trisaccharide backbone. Further O-deacetylation, azido group reduction and debenzylation of the protected trisaccharide precursor gave the corresponding trisaccharide amine. The latter structure was used in the synthesis of a series of trisaccharides bearing an acetyl group, an l-alanine or an N-acetylated l-alanine residue on its amino group at C-2 of GalN.

Graphical abstractThe first synthesis of a 3,4-vicinally branched trisaccharide related to glycoforms of the outer core region of the Pseudomonas aeruginosa lipopolysaccharide and its N-acylated, N-alanylated and N-(N-acetyl-alanylated) derivatives is described.Download full-size image