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Browsing by Author "McNaughton, Brian R., committee member"

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    Development of electrochemical imaging methods using micro-electrode arrays and microfluidic networks
    (Colorado State University. Libraries, 2016) Wydallis, John B., author; Henry, Charles S., advisor; Van Orden, Alan, committee member; Barisas, B. George, committee member; McNaughton, Brian R., committee member; Dandy, David S., committee member
    Distribution of molecules over space and time drive a multitude of macroscopic and microscopic biological processes. There is a need to design novel imaging techniques that can map molecular distributions with spatiotemporal resolution. In this thesis, new electrochemical approaches to provide spatiotemporal imaging are presented. The bulk of this work utilizes high-density platinum micro-electrode arrays fabricated using complementary metal oxide semiconductor (CMOS) fabrication techniques as well as microfluidics and carbon-based electrodes fabricated using soft lithography fabrication techniques. The systems described in this dissertation focus on quantification of biologically relevant neurotransmitters, mainly catecholamines and nitric oxide with concentration ranges from nM to mM. The pitch, or resolution between two "pixels" of electrochemical data, was 250 µm for microfluidic based sampling methods and 12.5 µm for the CMOS based sensors. Descriptions of fabrication methods for the carbon based electrodes and CMOS electrodes are described in this work. Finally, potential future directions of this technology is discussed in the final chapter.
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    Efforts toward the total synthesis of quinine, synthesis of largazole analogs, and progress toward potential biosynthetic intermediates of taxol
    (Colorado State University. Libraries, 2012) Bubb, Jennifer Marie, author; Williams, Robert M., advisor; Wood, John L., committee member; McNaughton, Brian R., committee member; Prieto, Amy L., committee member; Ishii, Douglas N., committee member
    Herein we discuss our work involving three different projects, namely (1) efforts toward the total synthesis of quinine, (2) synthesis of largazole analogs, and (3) progress toward potential biosynthetic intermediates of taxol. Our efforts toward the synthesis of quinine have led us toward a route toward a pipecolic acid derivative that was further elaborated to a late-stage intermediate. Following an intramolecular cyclization and deoxygenation protocol, a formal synthesis of quinine could be realized. In the second project, we have successfully synthesized and tested analogs of the known HDAC inhibitor, largazole. These analogs have demonstrated good potency towards a series of HDAC isoforms. In the third project, efforts have been made to synthesis potential biosynthetic intermediates of taxol. Utilizing highly oxygenated intermediates isolated from the heartwood of the Japanese yew tree, we have explored the reactivities of these complex natural products in hope of devising a method to construct mono-acetylated derivatives.
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    Organocatalytic, Michael-Stetter reaction and rhodium(I)-catalyzed hydroheteroarylation of acrylates with benzoxazoles: reaction development and investigations into origins of enantioselectivity
    (Colorado State University. Libraries, 2015) Filloux, Claire M., author; Rovis, Tomislav, advisor; McNaughton, Brian R., committee member; Prieto, Amy L., committee member; Crans, Debbie C., committee member; Hentges, Shane T., committee member
    The chapters that follow describe two independent investigations. Both relay the development of experimental methods for the catalytic, asymmetric addition of carbon-hydrogen bonds to alkenes. In the first chapter, nucleophilic amine and N-heterocyclic carbene cocatalysts cooperate in the organocatalytic, cascade synthesis of benzofuranone products in good yields and high enantioselectivities. Importantly, the cascade protocol is found to outperform a two-pot procedure in which reaction intermediates are isolated and purified before the second step. Mechanistic studies reveal that additives and geometry of an olefin intermediate crucially influence reaction enantioselectivity. In the second method, a bulky Rh(I)-bisphosphine complex catalyzes the asymmetric, intermolecular addition of benzoxazoles to methacrylate derivatives in fair to excellent yields and good to excellent enantioselectivities. Detailed deuterium labeling and epimerization studies provide considerable insight into the reaction mechanism: C-H activation is reversible; migratory insertion is likely enantiodetermining; and the bulky- bisphosphine ligand likely boosts reactivity and selectivity by discouraging deleterious ligation of benzoxazole starting materials to on- or off-cycle rhodium complexes and by impeding coordination-induced product epimerization.