Intra‐ and Intermolecular Glycosylation of d ‐Idopyranosyl and 6‐Deoxy‐ d ‐ ido ‐heptopyranosyl Donors: Toward the Repeating Unit of Campylobacter jejuni HS:4c Capsular Polysaccharide

The synthesis of disaccharide mimics of Campylobacter jejuni HS:4c capsular polysaccharide, a major pathogen associated with campylobacteriosis, is challenged by the presence of a 1,2‐ cis ‐β‐linked 6‐deoxy‐ d ‐ ido ‐heptopyranoside. Herein, the development of a synthetic route to orthogonally protected d ‐ ido ‐hexo‐ and 6‐deoxy‐ d ‐ ido ‐heptopyranosyl donors is reported bearing diverse anomeric leaving groups, which represents, to the best of knowledge, the second direct access to 6‐deoxy‐ d ‐ ido ‐heptopyranosides from ido ‐configured precursors. These donors were evaluated in intramolecular aglycon delivery (IAD) and intermolecular glycosylation protocols. While IAD enabled complete β‐stereoselectivity with hexosyl donors, it failed with the heptosyl analog. Intermolecular glycosylation provided mixtures of anomers, but the use of a 7‐ O ‐acetyl‐protected heptosyl donor allowed access to the disaccharide in good yield, with chromatographic separation of the α‐ and β‐anomers. Structural analysis revealed unexpected conformational behavior, with the α‐disaccharide adopting the 1 C 4 chair conformation. This work establishes a foundation for the synthesis of C. jejuni HS:4c disaccharides and represents a step toward well‐defined sugar‐based vaccines candidates against campylobacteriosis.