Thesis (PH. D.)--University of Nebraska, 1930. / Description based on print version record. Bibliography: p. 24.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1927. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 96-98).

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This thesis deals with the structure determination of some natural products in the molecular weight range 700 - 2000 daltons, using a combination of FAB mass spectrometry and proton NMR spectroscopy. Furthermore, the defined structural details have been used to investigate the driving forces behind molecular conformation and intermolecular interaction. The first section involves the structure elucidation of the saccharide portions of four glycosides isolated from a wild plant of potent pharmacological activity. The positive and negative ion FAS MS fragmentation pattern of six glycosides of known structure was investigated in order to ascertain the predictive power of the technique for unknown compounds of this class. With the saccharide sequence information determined using FAB MS studies, high resolution two-dimensional proton NMR spectroscopy was employed to identify the individual monosaccharide units and their order of linkage. In two cases, it was necessary to determine the spatial proximity of protons using spin-locking NMR techniques. In the second section, similar techniques were applied in the structure elucidation of a complex of glycopeptide antibiotics of the vancomycin family. The final structural details, identification of the fatty acyl groups, were resolved using chemical degradation/GCMS methods. In the third section, NMR experiments have been used to investigate the intramolecular determinants of conformation within the mobile regions of vancomycin. This includes exchange and rotational phenomena, and changes in molecular motion as the charge of the antibiotic is varied. The effects of the two protonated amino groups of vancomycin on the binding of models of bacterial cell wall peptides was examined. The amino groups are orientated such that they retain optimum exposure to the solvent whilst interacting with the bound peptide in two ways: <i>via</i> direct electrostatic interaction and <i>via</i> perturbation of the solvent, thus modifying the energetics of hydrophobic interactions. The conformational changes of ristocetin (in aqueous acetonitrile solution) on binding of model peptides were investigated. In addition, it was observed that ristocetin-peptide complexes dimerise at millimolar concentrations, and the geometry of the dimer was determined. The interactions that stabilise the dimer are remarkably similar to those that stabilise the peptide complex itself. Finally, possible roles for the sugars mannose and ristosamine in ristocetin, and vancosamine in canvomycin are discussed, with particular emphasis on the selectivity that they impose on the binding site of these antibiotics.