Synthesis and conformational analysis of vicinally branched trisaccharide β-d-Galf-(1 → 2)-[β-d-Galf-(1 → 3)-]-α-Galp from Cryptococcus neoformans galactoxylomannan

Abstract

The synthesis of a vicinally branched trisaccharide composed of two D-galactofuranoside residues attached via β-(1 → 2)- and β-(1 → 3)-linkages to the α-D-galactopyranoside unit has been performed for the first time. The reported trisaccharide represents the galactoxylomannan moiety first described in 2017, which is the capsular polysaccharide of the opportunistic fungal pathogen Cryptococcus neoformans responsible for life-threatening infections in immunocompromised patients. The NMR-data reported here for the synthetic model trisaccharide are in good agreement with the previously assessed structure of galactoxylomannan and are useful for structural analysis of related polysaccharides. The target trisaccharide as well as the constituent disaccharides were analyzed by a combination of computational and NMR methods to demonstrate good convergence of the theoretical and experimental results. The results suggest that the furanoside ring conformation may strongly depend on the aglycon structure. The reported conformational tendencies are important for further analysis of carbohydrate–protein interaction, which is critical for the host response toward C. neoformans infection.