| 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 glycosyl 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-alpha 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-beta 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. |
