Degree Type

Dissertation

Date of Award

2013

Degree Name

Doctor of Philosophy

Department

Chemistry

First Advisor

Nicola L. Pohl

Abstract

This document details the efforts towards the automated solution phase synthesis of fragments of the Xcc bacteria's lipopolysaccharide. The target fragment is a trisaccharide consisting of two glucosamine monomers with a 1-6 beta linkage connected to a 2-6 alpha link to 3-Deoxy-d-manno-Octulosonic Acid (KDO). First, the field of glycobiology is introduced and the challenges associated with the advancement of oligosaccharide synthesis highlighted. Then the synthesis of the glucosamine building block is described. Different approaches to the same general building block are investigated for the best possible route to the building block. Approaches that require less reaction steps, cheaper reagents, easier intermediates to handle, easier purification methods and safer reagents are sought and reported.

From the quest to produce easier intermediates, a different type of glycosyl donor, N-aryl trifluoroacetimidate donor is explored. Due to the change in stability observed with changing the substituent on the aryl group, stability studies of different methyl N-aryl trifluoroacetimidates are further studied. From the stability studies, the mechanism of acetimidate activation can be confirmed. Some acetimidates exhibit favorable characteristics and these are further studied for their role and ability as alkylating agents. Since some are crystalline at room temperature some acetimidates are reported for their appropriateness in commercialization.

The other part of the target LPS fragment is KDO and this rare and expensive sugar is synthesized through biosynthesis. Major problems with purification resulted in the chemical synthesis of KDO from oxaloacetic acid and this method also presents the same major problem. Future directions include better purification protocols for KDO and more runs of glucosamine building blocks on the automated solution phase workstation developed in the lab.

Copyright Owner

Sinele Banelile Tsabedze

Language

en

File Format

application/pdf

File Size

134 pages

Included in

Chemistry Commons

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