Site- and stereo-selective functionalization of sugars by C-H activation: the fucose case

Chemical modification of carbohydrates is significant for several scientific fields like biotechnology, medicine, materials science, and plays a crucial role in drug design and development. The modification of carbohydrate backbones through C-H activation is an emerging powerful approach for the non-enzymatic synthesis of rare sugars, many of which are found in naturally occurring antibiotics and other pharmaceuticals.1 It also holds a great potential in the context of designing glycomimetic ligands for lectin proteins. The ability to preserve the hydroxy group pattern of the anchor monosaccharide is critical for recognition, while the presence of additional functional groups is essential for enhancing affinity.2 Indeed, this allows to target secondary binding sites in lectins and/or to create multivalent ligand presentations, thus expanding the toolbox for glycomimetic development. Some work has been recently developed in this field,3 but selective activation of the C-5 position was never achieved. Here we report the development of an efficient method for the regio- and stereoselective C-5 modification of fucose via photo-mediated C-H activation to produce modified monosaccharides that we employed for molecular recognition in lectins.4