Stable and Easily Activated Thioglycosides for the Stereoselective Synthesis of Oligosaccharides

Louisiana State University, Baton Rouge LA

Investigators

Abstract

The Chemical Synthesis Program of the Chemistry Division supports the project by Professor Justin Ragains. Professor Ragains is a faculty member in the Department of Chemistry at Louisiana State University. He is developing synthetic methods for bonding monosaccharides to each other. These methods are critical for the synthesis of oligosaccharides. Oligosaccharides, in turn, play important roles in biology, most of which are poorly understood. Because of difficulties in isolation and purification, obtaining serviceable quantities of oligosaccharides for biological studies requires chemical synthesis. The synthesis of oligosaccharides suffers from a number of technological shortcomings including poor stability of chemical intermediates and technically challenging procedures; these limitations are being addressed by the current project. Scientific advances from this work result in improved syntheses of oligosaccharides, which in turn facilitate discoveries in biology and enable the development of oligosaccharide vaccines and therapeutics. Professor Ragains is committed to the scientific training of women and underrepresented minorities in the sciences and underprivileged students at all levels of education. Public outreach activities include summer chemistry lab activities for Baton Rouge high school students from underprivileged backgrounds. This project involves the development of 4-aryl-3-butenylthioglycosides (ABTGs) as a class of O-glycosylation electrophiles that combine the stability of thioglycosides with the straightforward activation of glycosyl trichloroacetimidates using catalytic acids. O-Glycosylation methods using ABTGs derived from sugars that are commonly found in mammalian oligosaccharides are under investigation. In addition, 1,2-cis-selective glycosylations with ABTGs that exploit their unusual mechanism of activation are being developed. Finally, a synthesis of the human milk oligosaccharide lacto-N-neotetraose using ABTGs as key intermediates is underway. This research program provides a series of O-glycosylation electrophiles in ABTGs that can be utilized by scientists with little training in chemical synthesis. The well-established utility of Boc- and Fmoc-protected amino acids has placed polypeptide synthesis within the reach of non-experts. Similarly, the ABTGs saccharides, when fully developed, place the synthesis of oligosaccharides in the hands of scientists who require these compounds for the study of glycobiology. The educational plan involves outreach to underprivileged high school students, many of whom are women and underrepresented minorities. Outreach activities include summer chemistry lab activities geared toward the development of laboratory skills that assist these students in college-level laboratory courses. Carbohydrate chemistry is a particular focus of these outreach activities.