Stereocontrolled Glycosylation under Cooperative Catalysis

Saint Louis University, Saint Louis MO

Investigators

Abstract

With the support of the Chemical Synthesis Program in the Division of Chemistry, Professor Alexei Demchenko of Saint Louis University will study new methods for glycosylation. Glycosylation is a reaction that connects simple carbohydrates together into oligomeric networks called glycans. Although glycans are desirable molecules for biological, medical, and industrial communities, complex carbohydrates are challenging targets for organic chemists. This research aims to investigate mechanistic and practical aspects of new glycosylation reactions discovered by the Demchenko group, thereby broadening their utility. The overall goal of this project is the invention of efficient approaches for the formation of critical glycosidic bonds in a highly selective manner. The project lies at the interface of organic, carbohydrate, and mechanistic chemistry. The development of such highly selective chemical reactions would provide access to structurally defined glycans for fundamental studies in chemical biology as well as for potential applications in developing diagnostic and therapeutic agents. Integral to the success of this program is the active participation of students of all levels including middle school researchers, who will receive solid training in research methods. This research program will provide opportunities for trainees to engage, learn, and grow through interactions with people from different backgrounds and education levels. The proposed study will investigate mechanistic and practical aspects of two new chemical reactions discovered by the Demchenko group during previous funding periods, Cooperatively catalyzed Koenigs-Knorr (4K) reaction and H-bond-mediated Aglycone Delivery (HAD) reaction. Under the scope of Objective A, the 4K reaction is to be improved and streamlined to yield a universal method for the direct activation of thioglycosides and other stable glycosyl donors under cooperative catalysis. Under the scope of Objective B, the 4K reaction and the HAD reaction will be combined into one universal “4K-HAD” platform in an effort to develop a superior method for stereoselective glycosylation. The methods under development have the potential to streamline the synthesis of all common glycosidic linkages and a broad range of biologically relevant glycan targets. Successful completion of the proposed research will not only advance the field of glycosylation but will also improve access to defined glycosylated systems for biological, and biomedical study. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.