Access To Galectin-3 Inhibitors From Chemoenzymatic Synthons

Chemoenzymatic strategies are useful for providing both regio- and stereoselective access to bioactive oligosaccharides. We show herein that a glycosynthase mutant of a Thermus thermophilus alpha-glycosidase can react with unnatural glycosides such as 6-azido-6-deoxy-D-glucose/glucosamine to lead to beta-D-galactopyranosyl-(1 -> 3)-D-glucopyranoside or beta-D-galactopyranosyl-(1 -> 3)-2-acetamido-2-deoxy-D-glucopyranoside derivatives bearing a unique azide function. Taking advantage of the orthogonality between the azide and the hydroxyl functional groups, the former was next selectively reacted to give rise to a library of galectin-3 inhibitors. Combining enzyme substrate promiscuity and bioorthogonality thus appears as a powerful strategy to rapidly access to sugar-based ligands.