Divergent Synthesis and Antigenicity Evaluation of Core Oligosaccharides of the Lipopolysaccharides from <i>Acinetobacter baumannii</i> SMAL and ATCC 19606

<i>Acinetobacter baumannii</i> poses a serious threat to human health. Pathogenic bacterial lipopolysaccharides (LPSs) are potent immunogens for the development of antibacterial vaccines. To investigate the antigenic properties of <i>A. baumannii</i> LPS, five well-defined core oligosaccharide fragments from the LPS of <i>A. baumannii</i> SMAL and ATCC 19606 were synthesized. A divergent synthesis strategy based on orthogonally protected α-(2 → 5)-linked Kdo dimer <b>6</b> was developed. Selective exposure of different positions in this key precursor and then elongation of sugar chains via stereocontrolled formation of both 1,2-<i>trans</i> and 1,2-<i>cis</i>-2-aminoglycosidic linkages permitted the efficient synthesis of the targets. The synthetic route also highlights a 4-<i>O</i> and then 7-<i>O</i> glycosylation sequence for assembly of the novel 4,7-branched Kdo framework. Antigenicity assay using the glycan microarray technique disclosed that tetrasaccharide <b>3</b> featuring both 4,7-branch and α-(2 → 5)-Kdo-Kdo structural elements was a potential antigenic determinant.