Design and Investigation of Highly Practical Glycosylation on the Development of Selectin Antagonist

Current progress on glycobiology and glycotechnology urge the development of various new drugs. As an example of the applicable studies based on the carbohydrate chemistry, there is the drug design of selectin antagonists which block the interaction between the selectin and its natural ligand, sialyl Lewis X (sLe^X). The highly effective synthesis of sLe^X is one of the important things for the investigation of selectin antagonists, for example, to establish a high-throughput screening (HTS) of active compounds. As a result, we succeeded the highly practical synthesis of sLe^X pentasaccharide and discovered a potent selectin antagonist, GSC-150, using the HTS. In addition, in order to establish a large scale synthesis of GSC-150, a one-pot glycosylation characterized by "Armed-Disarmed Coupling" was developed. This glycosylation was an applicable method for the synthesis of various Le^X analogs.