Glycosyl Sulfonates for the Construction of Difficult Glycosidic Linkages

Tufts University, Medford MA

Investigators

Abstract

With this award, the Chemical Synthesis Program of the NSF Chemistry Division is supporting the research of Professor Clay Bennett of Tufts University who is developing ways to make sugar molecules attach to each other at specific locations without forming mixtures of products. Being able to control the attachment of sugar molecules is important because it influences the reactivity of these compounds in different systems. Chains of sugar molecules are called oligosaccharides and are found on the surfaces of cells, are structural components of plants, and often control biological processes. Professor Bennett and his research group will determine which components of sugar molecules match best with a reagent to help form the desired connections. They will then test what they learn from these studies by making a known antibiotic compound. Determining how to make sugar molecules link together at specific locations will increase efficiency in oligosaccharide synthesis and decrease waste associated with separating mixtures of products. The results of this research impact all areas of activity that require carbohydrate synthesis, including agricultural, chemical, and pharmaceutical industries. This project also involves outreach activities to high school chemistry students to introduce the chemistry of sugar molecules. The Bennett lab is using sulfonyl chloride promoters to control the stereochemical outcome of glycosylation reactions of deoxysugars. These reactions are difficult to control due to the lack of a directing group so finding ways to achieve this selectivity is important. Three specific areas of investigation are being pursued: 1) monitoring the reactivity of different deoxy sugars and sulfonyl chlorides to create a database cataloging which promoter is best for which sugar, 2) determining the chemical interactions that control these transformations, and 3) demonstrating the utility of the method with the synthesis of saccharomicin B. Lessons learned from these studies may allow for the synthesis of challenging oligosaccharides without the need for wasteful separation procedures. This program will provide an excellent training environment for a diverse group of graduate, undergraduate, and high school students. 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.