Acinetobacter baumannii is currently posing a serious threat to global health. Lipopolysaccharide (LPS) is a potent virulence factor of pathogenic Gram-negative bacteria. To explore the antigenic properties of A. baumannii LPS, four Kdo-containing inner core glycans from A. baumannii strain ATCC 17904 were synthesized. A flexible and divergent method based on the use of the orthogonally substituted α-Kdo-(2!5)-Kdo disaccharides was developed. Selective removal of different protecting groups in these key precursors and elongation of sugar chain via αstereocontrolled coupling with 5,7-O-di-tert-butylsilylene or 5-O-benzoyl protected Kdo thioglycosides and 2-azido-2deoxyglucosyl thioglycoside allowed efficient assembly of the target molecules. Glycan microarray analysis of sera from infected patients revealed that the 4,5-branched Kdo trimer was a potential antigenic epitope, which is attractive for further immunological research to develop carbohydrate vaccines against A. baumannii.

An expedient synthesis of the nonreducing hexasaccharide fragment of axinelloside A has been completed via a linear stepwise glycosylation approach. Challenges involved in the synthesis include the highly stereoselective construction of five consecutive 1,2-cis-glycosidic linkages and the formation of a sterically crowded 2,3-disubstituted L-fucoside subunit. Protecting group-directing glycosylation strategies such as the remote participation effect of the benzoyl substituent and the stereocontrolling effect of the 4,6-O-benzylidene group were employed for the synthesis of the desired 1,2-cis-glycosidic linkages. Moreover, the 2,3branched L-fucoside framework was established through a 3-O and then 2-O glycosylation sequence in which the 3-hydroxyl group of the core L-fucose unit was glycosylated first and then the 2-hydroxyl. The synthetic hexasaccharide is properly protected, so it can be employed as a precursor to synthesize its natural form.

Acinetobacter baumannii is currently posing a serious threat to global health. Lipopolysaccharide (LPS) is a potent virulence factor of pathogenic Gram-negative bacteria. To explore the antigenic properties of A. baumannii LPS, four Kdo-containing inner core glycans from A. baumannii strain ATCC 17904 were synthesized. A flexible and divergent method based on the use of the orthogonally substituted α-Kdo-(2!5)-Kdo disaccharides was developed. Selective removal of different protecting groups in these key precursors and elongation of sugar chain via αstereocontrolled coupling with 5,7-O-di-tert-butylsilylene or 5-O-benzoyl protected Kdo thioglycosides and 2-azido-2deoxyglucosyl thioglycoside allowed efficient assembly of the target molecules. Glycan microarray analysis of sera from infected patients revealed that the 4,5-branched Kdo trimer was a potential antigenic epitope, which is attractive for further immunological research to develop carbohydrate vaccines against A. baumannii.