| dc.description | The C-polysaccharide is an antigen common to all known Streptococcus pneumoniae bacteria. The repeating unit in the C-polysaccharide is a pentasaccharide, which consists of the following sugars in order: two N-acetyl-D-galactopyranoses (A & B), ribitol phosphate (C), D-glucopyranose (D), and 2-acetamido-4-amino-2,4,6-trideoxy-D-galactopyranose (E), and with phosphorylcholine attached to C-6 of the A and B units (Figure 1.2). Successful syntheses of derivatives of the rare sugar E were developed. Many unsuccessful attempts were made to form the DE unit by two different strategies. Derivatives of the AB disaccharide were synthesized that had the required alpha-linkage between unit A and B and also a linker arm beta-linked to B. Use of solvent participation and careful control of reaction temperature allowed formation of the desired anomeric configurations with excellent stereoselectivity. It was found that phosphorylcholine units could be added regioselectively at both O-6s of the mostly unprotected AB-linker arm dimer. An improved synthetic route was developed to prepare an expensive reagent, D-galactal from D-galactose. The configurations and conformations of glycosyl sulfoxides were studied by X-ray crystallography, nOe experiments and DFT calculations. The evidence presented in this thesis shows that the most stable configurations of glycosyl sulfoxides are those that can adopt conformations with the aglycon exo and the lone pair on sulfur anti to the C1-O5 bond, because of the n → sigma* overlap possible in this orientation. For D-sugars, these are the SS configurations of the alpha-anomers. For glycosyl sulfoxides of alpha-anomers having the kinetically favored RS configurations, the anti conformations were found to be comparable in stability to the exo conformations, a surprising conclusion in view of literature assumptions. The calculations suggest that the anti conformation is stabilized by overlap of a p-type lone pair on the sulfoxide sulfur atom with the C1-O5 sigma* orbital. | en_US |
