Synthesis of Campylobacter jejuni capsular oligosaccharides and identification of a potential O-antigen against campylobacteriosis

The vaccines against campylobacteriosis are urgently needed because of the rising multidrug resistance of patho genic Campylobacter jejuni. The capsular polysaccharides of these bacteria, containing unique 6- deoxy- β- d- ido- heptopyranosyl or l- glycero- β- d- ido- heptopyranosyl residues, have emerged as attractive antigens. Expeditious assembly of the oligosaccharides derived from these glycans is challenging because β- d-idopyranosidic linkages are formidable to directly construct. Furthermore, whether the synthetic C. jejuni oligosaccharides could induce sufficient immunogenicity as the potential antigens remains unexplored. Here, we report a protocol for directly forming β- d- idopyranosidic bonds using α- d-6-deoxy-ido-heptopyranosyl, α- d-idopyranosyl, and d-/l- glycero- α- d- ido- heptopyranosyl ortho- hexynylbenzoates as glycosylating agents under gold(I) catalysis. To demonstrate the versatility of these methods, concise synthesis of conjugatable C. jejuni capsular di-/tetra-/hexa-/octasaccharides, having a backbone of [→3)-6-deoxy-β- d- ido-heptopyranosyl-(1→4)-2-acetamido-2-deoxy-β- d-glucopyranosyl (1→], has been achieved. The immunogenicity assessment of the glycoconjugates, prepared by conjugating the synthesized oligosaccharides to cross- reactive material 197, reveals the disaccharide as a potential O-antigen for developing vaccines against campylobacteriosis. This work should facilitate development of synthetic vaccines against Campylobacter infections. © 2025 the Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. no claim to original U.S. Government Works. distributed under a creative commons Attribution noncommercial license 4.0 (cc BY- nc).