This dissertation is composed of three different projects, each discussed in a chapter. Following are short descriptions of the contained chapters.Because of the low financial potential gains in antimicrobial drug development, companies have not invested into the area, relying on naturally occurring compounds found within the last twenty to thirty years to keep the microbes at bay. In the mean time, microbes are developing resistance to the most consistently used antimicrobials. Strains such as pseudomonas aeruginosa and methicillin-resistant staphylococcus are becoming more prevalent with the ubiquitous use of antimicrobials in animal feeds, cosmetics, and even medications. In order to contribute to the search for new antibiotics, we searched for antimicrobial lead compounds tapping an easily accessible resource-repurposed laboratory compounds. The first chapter of this dissertation addresses the process of organizing, testing, and analysis of a library for antibacterial assays. A few of the positive antibacterial hits have been analyzed to investigate the mode-of-action of their class.In another study, discussed in chapter two, addresses a total synthesis of Alexine, a polyhydroxylated pyrrolizidine found to exhibit antiretroviral activity. While most syntheses of this family of pyrrolizidines utilized amino acids or sugars as templates, this synthesis relied on an aza-payne rearrangement and a one-carbon homologative relay ring expansion after incorporation of all necessary carbons required in the structure of alexine. This synthesis attempt ends with the formation of the initial pyrrolidine via our methodology and a proposal for the completion of the total synthesis.In the final chapter, for which the dissertation has been titled, new advancements in halofunctionalization that have been uncovered in the Borhan laboratory are further investigated. In particular, the hypothesis regarding the enantioselectivities seen when utilizing (DHQD)2PHAL under optimized conditions suggests that the high enantioselectivities seen in the halofunctionalization of unfunctionalized alkenes done by Borhan and coworkers are due to the rigidity of DHQD ligand-linker bonds C-O-C=N facilitated by the sp2 character of pendant oxygen as it donates into the electron deficient aromatic linker. In order to probe this, a naphthalene linker analogue (DHQD)2NAPH was synthesized and used as a catalyst in the optimized reactions. Computational studies were used to confirm the results and confirm the validity of the hypothesis.
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