Reagent Controlled Selective Glycosylation Reactions with Deoxy-Sugar Donors

Tufts University, Medford MA

Investigators

Abstract

In this project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Clay S. Bennett of the Department of Chemistry at Tufts University will examine the development of methods for the stereoselective construction of deoxy-sugar linkages using shelf stable glycosyl donors. While approaches to deoxy-sugar construction do exist, they frequently rely on the use of temporary directing groups to control selectivity. This introduces multiple additional steps in their synthesis. The proposed research will involve developing a set of reagents to activate deoxy-sugar donors in such a fashion that they undergo SN2-like reactions, thereby eliminating the need for directing groups. Through proper choice of reagent it will be possible to selectively synthesize either diastereomer of a deoxy-sugar starting from the same glycosyl donor. Nuclear magnetic resonance spectroscopy studies directed at understanding the mechanism of these reactions will also be undertaken. The proposed research could lead to the creation of a modular set of reagent combinations for the facile construction of stereodefined glycosidic linkages with a broad set of substrates. By streamlining oligosaccharide construction, this chemistry will eliminate chemical waste arising from multiple solution-phase manipulations of temporary prosthetic groups and difficult purifications of diastereomers. Thus, it will also provide a more environmentally benign approach to these molecules. Importantly, the insights gained from mechanistic studies will guide the application of these methods to other classes of monosaccharides. Successful development of the methodology will impact all areas of activity that requires carbohydrate synthesis, including the pharmaceutical, chemical, agricultural industries, and the biological and chemical research communities. This project will also provide training for pre-undergraduate through graduate students, including students from groups that are historically underrepresented in the sciences.