Thesis (M.S.)--Tennessee Technological University, 2008. / Title from title page screen (viewed on May 12, 2010). Bibliography: leaves 54-58.

Inaug.-diss.--Zürich. / Lebenslauf. Includes bibliographical references.

Inaug.-diss.--Zürich. / Lebenslauf. Includes bibliographical references.

Thesis (Ph. D.)--University of Chicago, Dept. of Chemistry. / Includes bibliographical references. Also available on the Internet.

Thesis (Ph.D.) -- University of Rhode Island, 2007 / Typescript. Includes bibliographical references (leaves 144-148).

Thesis (Ph. D.)--University of Chicago, 1932. / Lithoprinted. "Private edition, distributed by the University of Chicago libraries, Chicago, Illinois." Description based on print version record. Bibliographical foot-notes.

This thesis describes expansion of the ability of isothioureas to act as organocatalysts in formal [2+2]-, [3+2]- and [4+2]-cycloadditions between carboxylic acids and various acceptors via Type I ammonium enolate intermediates. Chapter 2 describes the optimisation and investigation of [2+2]-cycloadditions from ammonium enolates and N-sulfonylimines as the two components. The development of this methodology allows successful access to highly stereodefined β-lactams and, following in situ ring-opening, β-aminoesters. The products are obtained from either preformed homoanhydrides or directly from carboxylic acids, using open flask conditions, from simple, bench-stable starting materials and is scalable. A variety of anti-β-lactams (21 examples, 46-68% yield, up to >95:5 dr, 21->99% ee) and β-aminoesters (9 examples, 44-74% yield, up to >95:5 dr, 68-92% ee) were accessed in moderate yield, excellent diastereo- and good enantioselectivity. This represents an improved route to anti-β-lactams over previously described ketene and N-triflyl imine based methods. Chapter 3 subsequently describes studies focussed on the use of ester surrogates in the formal [4+2]-cycloaddition reactions of isothiourea generated Type I ammonium enolates. Iso-propylphosphonate 163 proved highly effective as the four-component in this process, which following the in situ ring-opening of the initial dihydropyranone product allowed isolation of a range of novel diester products which were previously unobtainable using this methodology. The products were accessed in moderate to excellent yields, excellent diastereo- and enantiocontrol (9 examples, 12-63% yield, up to >95:5 dr, 67-99% ee) with this process also amenable to a large scale. Furthermore, selective reduction and acid-catalysed cyclisation allowed access to δ-lactone products in good yield with retention of stereocontrol. Finally, Chapter 4 describes work on isothiourea-catalysed formal [3+2]-cycloadditions of oxaziridines and acetic anhydrides gave access to stereodefined five-membered oxazolidin-4-one heterocycles. In this case, the use of preformed homoanhydrides and an inorganic base was imperitive to avoid reduction of the oxaziridine starting material. The oxazolidin-4-one products could be accessed in excellent yield and ee however poor dr (13 examples, 63-96% yield, up to 59:41 dr anti:syn, up to >99% ee for both diastereoisomers). Following isolation, reduction of these heterocycles allowed access to enantioenriched diols with little loss in stereocontrol. Mechanistic analysis has shown that an improvement in diasterocontrol can be obtained by the use of an enantioenriched oxaziridine, demonstrating the stereospecificity of this process.

No description available.

@font-face { font-family: "Arial"; }@font-face { font-family: "ＭＳ 明朝"; }@font-face { font-family: "Calibri"; }p.MsoNormal, li.MsoNormal, div.MsoNormal { margin: 0in 0in 0.0001pt; text-indent: 0.5in; line-height: 200%; font-size: 11pt; font-family: "Times New Roman"; }p.MsoBodyText, li.MsoBodyText, div.MsoBodyText { margin: 0in 0in 6pt; text-indent: 0.5in; line-height: 200%; font-size: 11pt; font-family: "Times New Roman"; }span.BodyTextChar { font-family: Calibri; }div.Section1 { page: Section1; } A 60 kDa monomeric protein isolated from the defensive purple ink secretion of the sea hare Aplysia californica has broad antimicrobial activity in tryptone peptone rich medium. This protein, which we call ‘escapin’, belongs to an L-amino acid oxidase family. The goals of my project were 1) to determine the products of escapin’s oxidation of its main substrate L-lysine, 2) to characterize the antimicrobial effects of escapin’s products, and 3) determine bactericidal mechanisms of action of these products. Escapin is a powerful bactericidal agent against several bacteria species including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Vibrio harveyi. Escapin operates through a two-step process: 1) deamination of L-amino acids (especially L-lysine) by enzymatic activity to produce escapin intermediate products of L-lysine (EIP-K), hydrogen peroxide, and ammonia; and 2) EIP-K simultaneously reacts with hydrogen peroxide to generate escapin end products (EEP-K). EIP exists as an equilibrium mixture of the linear a-keto analogue of lysine and its cyclic forms, and the relative amount of the linear form increases with pH decreases. The powerful bactericidal effect of escapin requires the simultaneous presence of hydrogen peroxide and EIP-K in weak acidic conditions, which suggests that linear form of EIP-K with hydrogen peroxide is responsible for the bactericidal effect of escapin. Using E. coli MC4100 as a model, the mechanism of action of escapin was examined. Brief treatment with EIP-K + H2O2, but not EIP-K or H2O2 alone, causes irreversible DNA condensation with a time course similar to the bactericidal effect. A mutant strain resistant to EIP-K + H2O2 was isolated, and a single point mutation was found in the oxidative stress regulator gene (oxyR). Through a complementary assay, it was shown that wild type E. coli is conferred resistance to EIP-K + H2O2 by carrying mutated oxyR plasmid. Furthermore, in this bactericidal effect, heat or cold shock does not substitute for hydrogen peroxide induced oxidative stress. Thus, escapin’s powerful bactericidal effect may be through irreversible DNA condensation mediated through hydrogen peroxide generating an oxidative stress response, but the pathway mediating EIP-K’s synergistic effect is still unclear.

No description available.