On the reactivity and selectivity of donor glycosides in glycochemistry and glycobiology

Abstract

The processes of glycosidic bond formation and destruction are a central theme in glycochemistry and glycobiology, and form the basis of the research described in this Thesis. In the first part, studies towards the stereoselective construction of two complex bacterial oligosaccharide fragments are described. These fragments contain mannuronic acid residues connected through a beta-linkage, which is amongst the most challenging linkages to construct synthetically. In the second part, the use of mannuronic acid building blocks in the automated synthesis of alginates using solid-phase chemistry is presented. Using a second-generation carbohydrate synthesizer, alginate fragments up to 12 residues were assembled with high stereoselectivity. Using the same automated set-up, fragments of hyaluronic acid of up to 15 residues were synthesized. In the third part, 2-deoxy-2-fluoroglucosides are investigated as activity-based probes for glucocerebrosidase, a retaining beta-glucosidase enzyme.NWO, TI PharmaUBL - phd migration 201