Doctor of Philosophy (PhD)
This dissertation focuses on analog synthesis for biological evaluation and visible light promoted method development. Chapter 1 centers upon the synthesis of Caenorhabditis elegans dauer pheromone analogs. C. elegans is a nematode which, in times of environmental stress, enters a dauer stage. Two highly conserved pathways, which play important roles in some diseases in higher organisms, monitor dauer formation: TGF-β and IGF-1. Dauer formation is triggered by the nematode’s chemosensation of the dauer pheromone, consisting of a group of previously-isolated ascarosides. These compounds differ in chain length, saturation, terminal functionality of side chain, ω vs. ω-1 oxygenation and presence of an indole-3-carboxyl protecting group. The roles that these various functionalities play in dauer formation are poorly understood. Therefore, analogs containing these functionalities are targeted for synthesis and biological evaluation in dauer formation assays to determine their structure-activity relationships. Chapter 2 concentrates on the synthesis of the infective juvenile (IJ) hormone of Heterorhabditis bacteriophora. This nematode exists in the soil as a robust infective juvenile, a “non-aging” and nonfeeding stage, homologous to the dauer stage of C. elegans. The hormone responsible for IJ formation and accumulation is isolated via bioassay-guided fractionation. This hormone’s structure is then elucidated, synthesized and evaluated for IJ formation activity. In Chapter 3 of this dissertation, a new method for seleno- and tellurofunctionalization is demonstrated. Selenocyclization has proven to be invaluable in the synthesis of complex natural products. However, it often involves the use of PhSeX (X = Br or Cl), which is a class of water-sensitive and toxic compounds. As a result, a visible light-promoted method is developed in which PhSeBr is generated in situ from the reaction of Ph2Se2 and CBr4, as determined by 77Se NMR. Selenofunctionalizations using this novel method with an array of substrates, including the total synthesis of Amaryllidaceae alkaloid, γ-lycorane, is accomplished in excellent yields. Chapter 4 describes the formation of an organic thin film using photocatalysis and aryl iodides. Most commonly, organic thin films are generated using thiol precursors. However, these thin films are often unstable to oxidation and thermal desorption. To circumvent these issues, a visible light photocatalytic method is developed where aryl radicals generated from aryl iodides are grafted to gold surfaces. The resulting thin films are extremely stable, due to the strength of the covalent carbon-gold bond. The multilayers were characterized using atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and water contact angle measurements.
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Balapitiya, Elizabeth Susan Conner, "I. Synthesis of Ascarosides for Biological Evaluation and II. Development of Visible Light-Promoted Selenofunctionalization and Grafting of Aryl Iodides" (2015). LSU Doctoral Dissertations. 637.