Reagent Controlled Selective Dehydrative Glycosylation Reactions

Tufts University, Medford MA

Investigators

Abstract

In this project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Professor Clay S. Bennett of the Department of Chemistry at Tufts University is developing new, efficient chemical approaches to combine single sugar molecules into chains of sugars called oligosaccharides. Oligosaccharides are found on the surfaces of cells and are important in mediating immune system responses. Reagent kits are being developed for the general construction of well-defined oligosaccharides much faster than is currently possible and with the production of less waste. This research program impacts science and technologies that utlize oligosaccharides, including agriculture, biotechnology and pharmaceutical science. Professor Bennett's group has an ongoing commitment to training undergraduate and graduate students in chemistry research methods. They are also involved in outreach to Somerville, MA high school students by providing them with an introduction to organic chemistry and how it can be used to create biologically relevant molecules. The community of Somerville is diverse, so this program reaches many students from groups that are historically underrepresented in STEM fields. Prof. Bennett is studying how to place the stereochemical outcome of a glycosylation reaction entirely under control of the promoter. For beta-selective glycosylations this involves activating hemiacetals with sulfonyl chlorides, while alpha-linked deoxy-sugars can be synthesized from hemiacetals using cyclopropenium cation promoted glycosylations. Three areas of investigation are being pursued: 1) an examination of the generality of this chemistry by exploring its compatibility with an array of deoxy-sugar coupling partners. 2) A study of the utility of this chemistry in the linear and convergent synthesis of penta- and hexasaccharides from natural products. 3) Studies to determine if this chemistry can be applied to the construction of beta-rhamnosides, an important class of carbohydrate linkages that currently cannot be synthesized directly in a single chemical transformation. Together, these studies may result in methods for the reliable stereoselective construction of difficult to access glycosidic linkages. Lessons learned from these studies also may permit the application of this chemistry to other classes of glycosides or even oligosaccharide and glycoconjugate libraries. Such libraries would open up new avenues for drug discovery and accelerate the pace of research in the field of glycobiology.