Degree

Doctor of Philosophy (PhD)

Department

Chemistry

Document Type

Dissertation

Abstract

Access to various oligosaccharides has been made possible by glycosylation reactions. This is mainly through chemical synthesis and enzymatic approaches. Herein, I talk about glycosylation through chemical synthesis. In general, glycosylation reactions lead to a mixture of 1,2-cis and 1,2-trans stereoisomers. Stereoselective access to 1,2-trans isomer is highly developed; it efficiently relies on neighboring group participation. However, efficient access to 1,2-cis selective glycosylation is still a work in progress. In Chapter 1, I highlight notable efforts developed so far that address the 1,2-cis selectivity challenge in glycosylation.

In Chapter 2, I demonstrate how I improved 1,2-cis selectivity using thioglycoside donors developed in our lab. The notable improvement in selectivity emanated from the synergy of electron-withdrawing protecting groups and 1,4-dioxane as solvent.

In Chapter 3, I employ findings from Chapter 2 on the usefulness of electron-withdrawing groups in improving the 1,2-cis selectivity of an already reported 1,2-cis selective protocol. Here, I observed significant improvements in selectivity just by switching from the use of well-known benzyl-protected imidate donors to para-trifluorobenzyl-protected imidate donors. I also show how this strategy is compatible with reactive acceptors.

Chapter 4 introduces Acinetobacter baumannii bacteria which are often resistant to most FDA-approved antibiotics. I describe two syntheses by others of glycans found in A. baumannii strains and how such glycans can be used in developing a vaccine against A. baumannii.

Chapter 5 illustrates my synthesis of a tetrasaccharide repeating unit expressed in A. baumannii strain D78. The synthesis was achieved in 33 steps starting from commercially available materials. The success of this tetrasaccharide assembly arose mainly from a stereoselective 2+2 glycosylation strategy.

Chapter 6 describes my 1+1+1+1+1 linear assembly strategy of a pentasaccharide which is highly expressed in multiple clinically relevant A. baumannii strains. The synthesis was achieved in 48 steps starting from commercially available starting materials. In this synthesis, a successful 3+1 regioselective glycosylation significantly reduced the total number of synthetic steps.

Date

7-16-2022

Committee Chair

Ragains, Justin

Available for download on Friday, July 07, 2023

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