Synthesis of oligosaccharides and conformational analysis by NMR spectroscopy

Abstract: The first part of this thesis describes investigations of the conformations of six N-linked pseudodisaccharides (Paper I), which were synthesized as glycosidase inhibitor candidates, and 10 β-D-xylopyranoside derivatives bearing hydrophobic aglycons (Paper II), by NMR spectroscopic methods. In paper I the ring conformations of 2- and 3-amino-α-D-altropyranosides, and ω torsions of altrosides, glucosides and mannosides were described, in neutral and protonated states. Occurrences of the conformations 4C1, oS2 and 1C4 were found for the altrosides, with large differences from the neutral to charged state observed for the 2-linked structures.The studied xylosides were found to predominantly reside in 4C1 conformation, with some population of 2So (˜5%), with exception of a 3-deoxygenated compound, which was found to be in equilibrium between the 4C1 and 1C4 conformations, and two epimerized compounds. The 3-deoxy compound was studied in further detail. The equilibrium was found to differ with temperature, and an estimate of the activation energy is presented.The second part describes synthesis towards N-glycan oligosaccharides with various fucosylation patterns. The synthesis involves a safe route to a glycosyl azide, a high-yielding conversion of the azide to acetyl amide and a stereoselective β-mannosylation performed by preactivation of the mannosyl donor. The synthesis of an orthogonally protected core trisaccharide is described.