Toward a User-Friendly Stereoselective Glycosylation Strategy
Abstract: All oligosaccharides are assembled from their corresponding
monosaccharide residues via glycosidic bonds. In chemical synthesis, these linkages are
formed by chemical glycosylation reactions. This dissertation studies the two fundamental
aspects of chemical glycosylations: 1): Stereocontrolled formation of glycosidic linkages
and 2): Design of chemical promoters to achieve user-friendly ... read moreglycosyl donor activations.
Chapter 1 first covers an overview of the biological relevance of carbohydrate molecules as
well as the important applications of synthetic chemistry in advancing glycobiology.
Following these background introduction, the second part of Chapter 1 reviews general
mechanisms of chemical glycosylations, and further discusses the respective
advantages/disadvantages of currently employed glycosyl donor activation approaches.
Chapter 2 discusses our contributions in tackling 1,2-cis-α glycosides. The synthetic
preparation of these linkages has long been considered a daunting task in glycochemistry.
The work in this dissertation resulted in the development of a new directing group-free
stereoselective glycosylation strategy. As these glycosidic linkages also commonly serve as
pathogenic determinants, we believe that this methodology will find broad applications in
synthetic vaccine projects. Chapter 3 and 4 are focused on the development of user-friendly
glycosylations with a new class of thiophilic promoter. Unlike most contemporary
approaches, the procedures developed here are characterized by their particular operational
simplicity. Later elaboration of these methods further accomplished 1,2-trans-β selectivity
without invoking the traditional neighboring acyl group participations. We anticipate that
these user-friendly glycosylation methodologies will ultimately lead to the development of
"glycosylation kits" that can be adopted by the wide chemical biology community, thereby
permitting the routine construction of carbohydrate samples.
Thesis (Ph.D.)--Tufts University, 2016.
Submitted to the Dept. of Chemistry.
Advisor: Clsy Bennett.
Committee: David Walt, Samuel Thomas, and Isaac Krauss.
Keywords: Chemistry, and Organic chemistry.read less