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.