Access to Galectin3 Inhibitors from Chemoenzymatic Synthons

Chemo-enzymatic strategies are useful to provide both regio-and stereoselective access to bioactive oligosaccharides. We show herein that a glycosynthase mutant of a Thermus thermophilus -glycosidase can react with unnatural glycosides such as 6-azido-6-deoxy-D-glucose/glucosamine to lead to -D-galactopyranosyl-D-glucopyranoside or -D-galactopyranosyl-2-acetamido-2-deoxy-D-glu-copyranoside 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.