CAREER: Stereocontrolled Synthesis of 1,2-cis Glycosides

University Of Missouri-Saint Louis, Saint Louis MO

Investigators

Abstract

This research project builds from the discovery of an unprecedented O-2/O-5 cooperative effect in the synthesis of oligosaccharides and glycoconjugates. Novel aspects of the glycosylation reaction and factors affecting its stereoselectivity will be explored. Major aims include the investigation of the mechanistic aspects of the cooperative effect in glycosylation and exploration of its application in stereocontrolled glycosylations. Bioorganic and carbohydrate chemistry will be incorporated as central components in the chemistry curriculum and in a variety of outreach activities at all levels. These activities include development and implementation of new organic chemistry courses, improvement of the laboratory curriculum, and establishment of regular symposia dedicated to glycosciences. With the support of this CAREER award from the Organic and Macromolecular Chemistry Program, Professor Alexei V. Demchenko, of the Department of Chemistry and Biochemistry at the University of Missouri at St. Louis, is developing new methods for the synthesis of organic molecules containing carbohydrate (sugar) units. Elucidation of the mechanisms of carbohydrate involvement in the pathogenesis of many human diseases is made difficult by the complexity and relatively low availability of relevant natural carbohydrate-based molecules. The main conceptual difference between oligosaccharides and other natural biopolymers, proteins and DNA, is in the nature of the sugar-sugar bond, which represents a new site requiring three-dimensional control of structure. The necessity to form such "glycosidic" linkages with complete structural control is a primary reason oligosaccharides remain amongst the most significant synthetic challenges of the 21st century. Professor Demchenko will also develop and implement new organic chemistry courses and revitalize the laboratory curriculum, incorporating central themes from bioorganic and carbohydrate chemistry, and will establish regular symposia dedicated to glycosciences.