Doctor of Philosophy (PhD)
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.
Njeri, Dancan Kamau, "Development of 1,2-cis-Selective Glycosylation Protocols and Multistep Synthesis of Glycans from Acinetobacter baumannii." (2022). LSU Doctoral Dissertations. 5905.