Degree
Doctor of Philosophy (PhD)
Department
Chemistry
Document Type
Dissertation
Abstract
The symbiotic relationship between humans and their microbiota is essential for health, with imbalances in the complex microbiota ecosystem linked to a variety of disorders ranging from neurodegenerative to gastrointestinal diseases. Bacteria within the human microbiota, comprising over 1000 known species, are densely and diversely coated with oligosaccharides crucial for functions like cell recognition, communication, signaling, adhesion, proliferation, and pathogenic inhibition. However, studying the structure-activity relationships of these sugars which are also secreted by bacteria is challenging due to difficulties in obtaining homogenous samples from natural sources.
Chemical synthesis offers a solution by enabling the production of well-defined oligosaccharides in reliable, homogenous quantities, which are invaluable as biochemical tools and therapeutics. Despite their abundance as the third most common monosaccharide in bacterial oligosaccharides, 1,2-cis glucosides are particularly difficult to synthesize due to complex protocols, hazardous reagents, poor stereoselectivity, cryogenic conditions, and the need for specialized protecting and leaving groups. My research addresses these challenges by developing simpler and more effective methods for the synthesis of 1,2-cis glucosides, advancing our ability to study and utilize these important molecules.
In Chapter 1, I discuss the background and significance of 1,2-cis glucosides and how synthetic glycans have benefited society as biochemical tools and therapeutics. In Chapter 2, I discuss various approaches for 1,2-cis-selective glycosylation and present my findings in using electron-withdrawing protecting groups for a highly selective 1,2-cis-selective glucosylation. This method demonstrates applicability under a variety of reaction conditions. In Chapter 3, I introduce a novel stereoinverted glycosylation method using simple benzyl chalcogenoglycoside donors and benzyne. Utilizing Kobayashi reagent as a benzyne precursor, this distinct approach achieves exceptionally high 1,2-cis stereoselectivity without the need for specialized protecting groups, leaving groups, and cryogenic temperatures. In Chapter 4, I detail the development of a visible-light photochemical glycosylation method involving selenoglycoside donors and Umemoto reagent to form electron donor-acceptor complexes. This method produces high yields, moderate to high 1,2-cis selectivity, and is suitable for flow chemistry. Evidence for non-covalent interactions and discovery of an alternative mode of visible-light-activated glycosylation is also presented.
Date
7-16-2024
Recommended Citation
Alvarez Valenzuela, Erik Giovanni, "Advances in Stereoselective Glycosylation: Electron-Withdrawing Groups, Benzyne-Mediated Stereoinversion, and Visible-Light Photochemistry for 1,2-cis O-Glycosylation" (2024). LSU Doctoral Dissertations. 6573.
https://repository.lsu.edu/gradschool_dissertations/6573
Committee Chair
Justin Ragains