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Browsing by Author "Wood, John L., committee member"

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    Application of metallacycles for the synthesis of small molecules
    (Colorado State University. Libraries, 2011) Williams, Catherine Marie, author; Rovis, Tomislav, advisor; Wood, John L., committee member; Finke, Richard G., committee member; Shores, Matthew P., committee member; McNeil, Michael R., committee member
    A method for the nickel-catalyzed hydrocarboxylation of styrene derivatives has been developed that affords exclusively the branched carboxylic acids in moderate to excellent yields. The reaction scope is tolerant of a variety of electron-deficient ortho-, meta-, and para-styrene analogues containing ester, ketone, nitrile, and halide functionalities. The reaction is remarkably efficient, proceeding well with as little as 1 mol% Ni(acac)2 and 2 mol% Cs2CO3. A system for carbon dioxide sequestration and release in organic polymers has been investigated. Although evidence supporting successful carbon dioxide fixation has been found, the envisioned system is not a practical means of sequestration and release. A rapid approach for the synthesis of Abyssomicin C has been developed utilizing the desymmetrization of meso-dimethylglutaric anhydride. Closely modeled after Sorensen's synthesis, our route bypasses the more inefficient beginning steps to intercept the completed synthesis at the Diels-Alder precursor.
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    Approaches towards the synthesis of saxitoxin alkaloids
    (Colorado State University. Libraries, 2013) Pearson, Aaron Daniel, author; Williams, Robert M., advisor; Wood, John L., committee member; Kennan, Alan J., committee member; Fisher, Ellen R., committee member; Woody, Robert W., committee member
    Zetekitoxin AB is a toxin isolated from the Panamanian golden frog (Atelopus zeteki). The structure and activity of zetekitoxin AB was a mystery for 30 years until 2004 when it was elucidated by Yamashita and coworkers. It was found to be a potent analog of Saxitoxin, a marine neurotoxin. Saxitoxin is a sodium channel blocker and has been used extensively as a research probe. Zetekitoxin AB shows an affinity profile similar to saxitoxin, but is considerably more potent. Due to the endangerment of the Panamanian golden frog there is no source of zetekitoxin AB, preventing further studies. Presented herein is a concise synthesis of 4,5-epi-11-hydroxy-saxitoxinol, which utilizes D-ribose to direct an asymmetric Mannich reaction. This approach allows many modes of reactivity, which can be used to potentially access various analogs of saxitoxin with novel bioactivity.
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    Development of an asymmetric intermolecular stetter reaction and organocatalyst design
    (Colorado State University. Libraries, 2012) Glover, Garrett S., author; Rovis, Tomislav, advisor; Wood, John L., committee member; Kanatous, Shane, committee member
    The intermolecular Stetter represents a powerful carbon-carbon bond forming reaction that involves addition of an acyl anion equivalent to an untethered Michael acceptor. Despite the appeal of rendering the intermolecular reaction asymmetric, this area remains particularly underdeveloped. We describe a catalytic asymmetric intermolecular Stetter reaction for the coupling of 2-pyridinecarboxaldehydes and β-substituted vinyl triflones. In pursuit of increasing the efficiency of this reaction, we developed a series of base-activated NHC pre-catalysts that are capable of catalyzing the intramolecular Stetter reaction without an external base. As an indirect result of our attempts to form activated pre-catalysts, we discovered a catalyst hydration product, that itself generates free-carbene in solution. Additionally, we gathered conclusive evidence for a previously unknown SNAR type decomposition pathway of an electron deficient triazolinylidene catalyst.
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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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    Epidithiodioxopiperazines: synthetic studies of (+)-chetomin and (-)-sporidesmin A
    (Colorado State University. Libraries, 2012) Welch, Timothy R., author; Williams, Robert M., advisor; Rovis, Tomislav, committee member; Wood, John L., committee member; Ackerson, Chris, committee member; Thamm, Douglas H., committee member
    This dissertation documents efforts toward the asymmetric total syntheses of the natural products (+)-chetomin and (-)-sporidesmin A. Synthetic methods have been developed to efficiently construct the dioxopiperazine core of both molecules. Additionally, a simple epidithiodioxopiperazine has been synthesized to demonstrate a general method for the addition of a sulfur bridge to a dioxopiperazine ring. The work described herein, while not totally successful, provides a basis for future completion of the asymmetric total syntheses of these two epidithiodioxopiperazines and other related fungal metabolites.
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    Mechanistic investigations and ligand development for rhodium catalyzed [2+2+2] and zinc catalyzed [4+2] cycloadditions
    (Colorado State University. Libraries, 2013) Dalton, Derek M., author; Rovis, Tomislav, advisor; Wood, John L., committee member; Kennan, Alan J., committee member; Rappé, Anthony K., committee member; Snow, Christopher D., committee member
    Described herein are mechanistic studies and ligand development for Rh(I) catalyzed [2+2+2] cycloaddition reactions of alkene tethered isocyanates and exogenous alkynes. A mechanistic hypothesis has been proposed and supported through experiment. Novel perfluoroaryl Taddol phosphoramidite ligands were developed based on the mechanistic hypothesis. Improvements in product and enantioselectivity were found using the perfluoroaryl Taddol phosphoramidite ligand, CKphos. This catalyst system was studied by NMR, X-ray and DFT calculations. Rh(I)-C6F5 and Co(-1)-C6F5 interactions were found in the course of studying the CKphos catalysts. The Rh-CKphos catalyst system was used in the synthesis of the tricyclic core structure of the cylindricine and lepadiformine alkaloids. Finally a Zn(II)-catalyzed [4+2] cycloaddition of 1- azabutadienes and nitro olefins was discovered and developed as an efficient and selective means to synthesize tetrahydropyridines.
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    N-Heterocyclic carbene catalysis: application to the total synthesis of cephalimysin A, and development of multicatalytic cascade reactions
    (Colorado State University. Libraries, 2011) Lathrop, Stephen Paul, author; Rovis, Tomislav, advisor; Wood, John L., committee member; Crans, Debbie Catharina, committee member; Shores, Matthew P., committee member; Kanatous, Shane B., 1968-, committee member
    Application of the N-Heterocyclic carbene catalyzed Stetter reaction to the total synthesis of 9-epi-cephalimysin A has been realized. The approach centers on the use of an asymmetric catalytic Stetter reaction to access the spirocyclic core of cephalimysin A. Specifically it was found that a photoisomerization/Stetter protocol allows rapid access to an intermediate readily amenable for further functionalization. This intermediate was further elaborated to three stereoisomers of the naturally occurring cephalimysin A. During the investigation of cephalimysin A an interesting side product was observed that led to the development of several multicatalytic cascade reactions utilizing N-heterocyclic carbenes. Specifically the pairing of secondary-amine catalysts with N-heterocyclic carbenes allowed for the synthesis of densely functionalized cyclopentanones in a single step. Moreover, a synergistic relationship was observed between the two catalysts. This partnership allowed for the products to be achieved in higher selectivity than would have been possible if conducting the reactions in a stepwise fashion.
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    Studies on the biosynthesis of the stephacidins and notoamides. Total synthesis of notoamide S and notoamide T. and Progress toward the synthesis of chrysogenamide A
    (Colorado State University. Libraries, 2011) McAfoos, Timothy Jospeh, author; Williams, Robert M., advisor; Kennan, Alan J., committee member; Wood, John L., committee member; Finke, Richard G., committee member; Crick, Dean C., committee member
    Herein I discuss my efforts toward the elucidation of the biosynthesis of the stephacidins and notoamide family of natural products. Notoamide S has been suggested to be the final common precursor between two different fungal strains, Aspergillus sp. and Aspergillus versicolor, before diverging to form enantiomerically opposite natural products (+) and (-)-stephacidin A and (+) and (-)-notoamide B. The synthesis of notoamide S comes from coupling N-Fmoc proline with a 6-hydroxy-7-prenyl-2-reverse prenyl tryptophan derivative synthesized through a late stage Claisen rearrangement. The oxidation of notoamide S affords an achiral azadiene that leads to an intramolecular Diels-Alder providing a new product, notoamide T, containing the bicyclo[2.2.2]diazaoctane ring system with the 6-hydroxy-7-prenyl indole ring of notoamide S. The synthesis of notoamide T is accomplished through a radical addition to the pyran ring of stephacidin A followed by an elimination ring opening event to provide the 6-hydroxy-7-prenyl indole. Chrysogenamide A is the newest member of the marcfortine family of natural products. Herein I discuss the synthesis of 7-prenyl-2-reverse prenyl indole through a thio-Claisen reaction and subsequent Lewis acid mediated sulfide removal. Coupling of a pipecolic acid derivative with the 7-prenyl-2-reverse prenyl tryptophan leads to the dipeptide containing all of the carbons needed in chrysogenamide A. I propose that chrysogenamide A can be synthesized through an unprecedented intramolecular Diels-Alder reaction of a monoketopiperazine by a condensation/tautomerization event leading to the appropriate azadiene for the intramolecular Diels-Alder reaction. A final oxidation of the intramolecular Diels-Alder product would lead to chrysogenamide A and what could be a newly proposed biosynthesis of a monoketopiperazine.
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    Synthetic studies on (-) lemonomycin: construction of the tetracyclic core
    (Colorado State University. Libraries, 2013) Jiménez-Somarribas, Alberto, author; Williams, Robert M., advisor; Wood, John L., committee member; Shi, Yian, committee member; Ladanyi, Branka M., committee member; Crick, Dean C., committee member
    Documented herein are efforts towards the asymmetric total synthesis of (-)-lemonomycin, a member of the tetrahydroisoquinoline antitumor antibiotics family of natural products. We describe a concise route for the assembly of the tetracyclic core of this molecule, which involves a Pictet-Spengler reaction for the construction of the tetrahydroisoquinoline fragment and an azomethine ylide [3+2] dipolar cycloaddition for the construction of the diazabicyclo[3.2.1]octane ring system. The above-described synthetic efforts, while not totally successful, provide the basis for the future completion of the total synthesis of this natural product and other related compounds.
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    Total syntheses of (±)-fawcettimine, (±)-fawcettidine, (±)-lycoflexine, and (±)-lycoposerramine B
    (Colorado State University. Libraries, 2012) Pan, Guojun, author; Williams, Robert M., advisor; Henry, Charles, committee member; MacNeil, Maechael, committee member; Rovis, Tomislav, committee member; Wood, John L., committee member
    The total syntheses of (±)-fawcettimine, (±)-lycoflexine, (±)-fawcettidine, and (±)-lycoposerramine B have been accomplished through an efficient, unified, and stereocontrolled strategy that required sixteen, sixteen, seventeen, and seventeen steps, respectively, from commercially available materials. The key transformations involve: 1) a Diels-Alder reaction between a 1-siloxy diene and an enone to construct the cis-fused 6,5-carbocycles with one all-carbon quaternary center, and 2) a Fukuyama-Mitsunobu reaction to form the azonine ring. Access to the enantioselective syntheses of these alkaloids can be achieved by kinetic resolution of the earliest intermediate via a Sharpless asymmetric dihydroxylation.