Synthesis of multivalent b-1-thiogalactosides through azide-symmetric alkyne Ru(II)-catalyzed cycloaddition

JOSÉ KOVENSKY; ALEJANDRO JAVIER CAGNONI; VARELA, OSCAR; MARÍA LAURA UHRIG

Sorrento

Congreso; 16th european Carbohydrate Symposium; 2011

International Carbohydrate Organization

As part of our ongoing project on the synthesis of multivalent glycoclusters designed to be hydrolytically stable in biological media, we describe here the synthesis of multi-thiogalactosides using as key step the Ruthenium(II)-catalysed cycloaddition of azidosugars and a disubstituted (internal) alkyne chain carrying two thiogalactoside residues. A symmetric divalent 1-beta-thiogalactoside precursor (1) has been synthesized from an diethyleneglycol-type linker functionalized with an internal triple bond. On the other hand, azide-containing scaffolds as 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl azide and the per-O-acetyl-6,6?-diazidotrehalose 2 were prepared by previously reported methods. Coupling of 1 to the selected sca# olds was achieved by Ru(II) catalyzed cycloaddition, using chloro(pen tamethylcyclopentadienyl) (cyclooctadiene)ruthenium(II) complex as catalyst, in dioxane as solvent. Glycoclusters containing two or four residues of 1-beta-thiogalactose have been obtained in good yields. deacetylation with Et3N/MeOH/H2O led to the $ nal products. After complete characterization by NMR spectroscopy and HR-MS techniques, these new multivalent ligands have been evaluated as inhibitors of E. coli beta-galactosidase. These compounds are interesting as potential modulators of lectin-mediated processes.