Degree Type

Dissertation

Date of Award

2009

Degree Name

Doctor of Philosophy

Department

Chemistry

First Advisor

Nicola L. Pohl

Abstract

This dissertation describes 1) the synthesis of disaccharide standards for mass spectrometry-based carbohydrate sequencing and 2) the automated iterative solution-phase synthesis of beta-glucans. Two libraries of mass-identical disaccharides were synthesized. Varying in linkage position and the identity of the non-reducing end monosaccharide residue, these compounds served as synthetic standards for systematic study by tandem mass spectrometry. These disaccharides were analyzed by mass spectrometry in the laboratories of Professors Edward Yeung and Young-Jin Lee. The varying degrees of fragmentation observed in the MS-MS spectra of several of these disaccharides were used to produce classification functions that were capable of correctly classifying the linkage position and identity of the non-reducing end monosaccharide residue. These results provide insight that will ultimately contribute to the development of faster carbohydrate sequencing methods.

The second portion of this dissertation describes the automated solution-phase syntheses of branched and linear beta-glucans. A fluorocarbon-based tag on the growing sugar chain allows for facile purification of intermediates by automated fluorous solid-phase extraction (FSPE), and also provides a means of noncovalent attachment to a fluorinated glass slide for the direct formation of carbohydrate microarrays. Our synthetic approach allows for traditional solution-phase kinetics, reaction monitoring, and chromatographic purification, techniques that are not possible with solid-phase oligosaccharide synthesis. Several new glucosyl trichloroacetimidate building blocks were synthesized and subsequently utilized for the automated synthesis of branched and linear beta-glucan fragments. Finally, conditions were developed to fully deprotect our synthetic glucans, rendering them suitable for NMR binding studies and biological assays. These studies established automation protocols that can be used for the synthesis of larger, more complex beta-glucan structures.

Copyright Owner

Steven Michael Brokman

Language

en

Date Available

2012-04-30

File Format

application/pdf

File Size

296 pages

Included in

Chemistry Commons

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