Synthesis of 1,2,3-triazole-linked galactohybrids and their inhibitory activities on galectins

Abstract

Here a synthesis of novel galactose-1,2,3-triazole conjugates is described. The title compounds were obtained from 3-azido-3-deoxy-1,2:5,6-di-O- isopropylidene-α-D-galactofuranose via a copper catalyzed azide-alkyne 1,3-dipolar cycloaddition reaction. It was demonstrated that the title compounds in their isopropylidene-protected form tend to chelate copper. The copper content can be diminished to 10 ppm by successive treatment with EDTA and Na2S followed by chromatographic purification. Acidic hydrolysis of the acetonide protecting groups provided water soluble galactohybrids that were tested for their affinity towards galectin-1 and galectin-3. The trimeric galactohybrid exhibited a 160-fold preference for galectin-3 binding with Kd 50 μM. One of the obtained disaccharides was characterized by X-ray analysis. © ARKAT-USA, Inc.