Doctor of Philosophy (PhD)
This dissertation focuses on the synthesis of dauer pheromone analogs for biological evaluation, the development of visible light promoted O-glycosylation methods and the development of an Ir(ppy)3 catalyzed C-H hydroxylation method. Chapter 1 describes the synthesis of dauer pheromone analogs. C.elegans is a small nematode that enters a dauer stage when encountering unfavorable environmental conditions. The dauer stage is initiated by the nematodes chemosensation of the dauer pheromone caused by the down regulation biochemical pathways TGF-â and IGF-1. These biochemical pathways are also seen in Homo Sapiens and play a role in a number of biological processes. Understanding how these pathways work in C.elegans can give us a better understanding of how they function in humans. In order to see the effect structure has on binding to the GCPR’s that initiate dauer formation a series of dauer pheromone analogs differing in chain length and degree of unsaturation were synthesized. These analogous were then tested to see there dauer inducing activity to give a structure to activity relationship. Chapter 2 centers upon the development of an alpha selective glycosylation of alcohols with selenoglycosides using visible light. Selenoglycosides are highly stable glycosyl donors. There stability is useful in oligosaccharide synthesis. This stability, however, requires harsh reaction conditions to activate them. The development of a mild and easily performed O-glycosylation method using selenoglycosides is described here. Chapter 3 focuses on the development of a metal free, visible light promoted O-glycosylation method using thioglycosides. Thioglycosides like selenoglycosides are commonly used in oligosaccharide synthesis. The harsh reaction conditions used to activate them has been a long standing issue in the carbohydrate community. The development of a mild, catalyst free O-glycosylation method using thioglycosides is described here. The method uses 4-methoxyphenyl-3-butenylthioglucoside donors in the presence of easily handled and bench stable Umemoto’s reagent to provide good yields of disaccharides, it is selective for the â-anomer when using the glycosyl donor with an acetate group at the 2- position, and the method is orthogonal. Chapter 4 details the development of a C-H hydroxylation method using fac-Ir(ppy)3 catalyst. 1-6 and 1-7-hydrogen atom transfers from unactivated aliphatics were performed with the aid of a Tzo directing group. The resulting radical then underwent redox chemistry followed by attack of water to give hydroxylated products in moderate yield.
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Spell, Mark Louis, "Visible Light and Electron Transfer Chemistry for O-Glycosylation and Remote Hydroxylation" (2016). LSU Doctoral Dissertations. 2520.