Fluorinated carbohydrates

Fluorination is an extremely useful tool to probe and modulate carbohydrate-protein interactions. We focus on the synthesis of fluorocarbohydrates, especially fluorinated oligosaccharides, and their use as glycomimetic probes of carbohydrate-protein interactions. Our particular interest is to employ fluorinated oligosaccharides as selective ligands for galectins, a biomedically significant class of carbohydrate-binding proteins. We are developing methods for the preparation of fluorinated glycosyl donors and acceptors, and studying their reactivity and stereoselectivity in glycosylation. Systematic regio- and stereoselective fluorination of each position within the sugar skeleton permits to site-selectively decouple each individual carbohydrate hydroxyl from the hydrogen-bonding network within the glycan chain and evaluate its influence on conformation, lipophilicity, and other properties. Similarly, systematic fluorination can reveal the contribution of each position within the oligosaccharide framework to glycan-protein interaction.  In addition, new binding interactions can be introduced by fluorination in some cases. Taking advantage of the favorable NMR properties of the ¹⁹F nucleus, we can investigate carbohydrate-protein interactions through ¹⁹F NMR-based experiments.