Project Summary
The emergence of drug resistant microbial strains has posed a great threat to the global
human health. To prevent bacterial infections and reduce our reliance on antibiotic
treatment, development of alternative effective approaches is extremely urgent. Invasive
bacteria often produce unique and complex cell surface glycans, e.g. capsular
polysaccharides (CPS), whose structures are significantly different from human glycome.
These microbial glycans are essential virulence factors for pathogen invasion and
promising targets for the development of effective vaccines for preventing bacterial
infections. Glycan-based antimicrobial vaccines are often prepared by conjugation of
capsular polysaccharides to a protein carrier. Currently, glycan antigens are mainly
obtained from bacterial fermentation. Hence, it is difficult to control the quality and length
of glycans. In order to prepare homogeneous fully synthetic glycoconjugate vaccines,
chemical synthesis remains as a reliable approach to access sufficient quantities and
good purity of bacterial carbohydrate molecules. Structurally, microbial glycans often
consists of unusual and highly complex monosaccharides as well as challenging
glycosidic linkages. Therefore, their chemical synthesis demands the development of
new efficient glycosylation methods and strategies. In this application, two new catalytic
glycosylation methodologies will be developed including: 1) a cationic gold(I)-catalyzed
glycosylation involving glycosyl N-1,1-dialkylpropargyl carbamate donors, and 2) a
cesium-catalyzed anomeric O-alkylation for stereoselective construction of ß-mannoside
type linkages. Synthesis of representative antigenic oligosaccharide repeating units from
harmful bacteria, such as Salmonella strains, Bacillus anthracis and Bacillus
stearothermophilus will be carried out employing these newly developed glycosylation
methods.