Stereoselective Synthesis and Immunological Evaluation of α‐ and β‐Linked Legionaminic Acid Glycoconjugates

Abstract

Legionaminic acid (Leg) is a bacteria‐specific nonulosonic acid that has emerged as a promising target for the development of pathogen diagnostics and vaccines, especially against critical‐priority Acinetobacter baumannii . However, immunological studies of Leg‐containing glycoconjugates remain largely unexplored due to the limited availability of structurally well‐defined Leg glycosides. Herein, we developed an additive‐controlled glycosylation strategy using a 5‐ N ,4‐ O ‐carbonyl‐protected Leg thioglycoside donor, which enabled the stereoselective synthesis of both α‐ and β‐linked Leg glycosides. To assess their immunological properties, these Leg glycosides were further elaborated into two Leg5,7NAc2‐CRM197 glycoconjugates. Immunological evaluation revealed that Leg functions as an antigenic epitope whose antibody specificity is governed by its anomeric configuration.