Synthesis of 3-Azidopropyl-Functionalized GalNAc-β-(1→4)-Gal Natural Disaccharide

Oligosaccharides such as the GalNAc-β-(1→4)-Gal disaccharide are involved in host-pathogen interactions and their synthesis is a continuing challenge for organic chemists. Only a few reports have discussed the synthesis of functionalized GalNAc-β-(1→4)-Gal for its further conjugation and applications in glycobiology. The synthetic route described here is taking advantage of (1) a simple and affordable GlcNAc donor which is epimerized to the more expensive GalNAc donor and (2) a 1,6-anhydro-galactose acceptor exalting the reactivity at the 4-position of galactose. The allyloxycarbonyl (Alloc) protecting group used at the 2-position of the GalNAc residue was important (1) for a successful epimerization of the GlcNAc residue into the corresponding GalNAc donor but also (2) for the stereoselective β-glycosylation through anchimeric assistance. The key disaccharide intermediate was further transformed to a trichloroacetimidate donor which could then be glycosylated with any alcohol. The example chosen here is the 3-azidopropyl aglycon for the design of multivalent glycoclusters.