Thesis (PH. D.)--University of Nebraska, 1938. / eContent provider-neutral record in process. Description based on print version record. Bibliography: p. 38-41.

Dissertation--Hamburg, 1925. / Lebenslauf.

The reaction of various 2-nitrobenzaldehyde derivatives with methyl vinyl ketone (MVK) in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) has afforded the Baylis-Hillman adducts in moderate to good yield. Dissolution of the catalyst in the solvent before the addition of the aldehyde was observed to improve the yield. Reduction of the Baylis-Hillman adducts was effected by catalytic hydrogenation using a 10% palladium-on- carbon catalyst in ethanol to give quinoline and quinoline-N-oxide derivatives and, in some cases, acyclic reduction products. All products were characterised using NMR and, where appropriate, HRMS methods. Selected quinoline-N-oxides were successfully converted to their corresponding quinoline derivatives using phosphorus tribromide (PBr₃) and DMF as solvent. Conjugate addition of the benzylamine and piperidine nucleophiles to the Baylis-Hillman adducts was also investigated but proved problematic, with one of the substrates undergoing a retro-Baylis-Hillman reaction to afford the aldehyde in ca. 40% yield, but seemingly only traces of the required product. Perkin-type coupling of two 2-methylquinolines with benzaldehyde was successfully effected to afford the desired styrylquinoline derivatives confirming the potential of the Baylis-Hillman approach to the construction of the analogues of known HIV-1 integrase inhibitors. Three ¹³C NMR chemical shift prediction programmes, viz., Chem Window, neural network and HOSE (hierarchically ordered spherical description of environment) methods were applied to selected representative compounds prepared in the project. The results from the three programmes correlated reasonably well with the experimental carbon-13 chemical shift data for each of the selected compounds.

The molecular events in cells exposed to mutagenic and oncogenic quinoline N-oxides were examined by analyzing single-strand breakage of DNA. Secondary cultures of embryonic Syrian-hamster cells and a line of BHK-21 cells were used. The choice of nitroquinoIine N-oxides afforded a series of water-soluble chemicals with three relative degrees of oncogenicity: highly oncogenic 4-nitroquinoIine 1-oxide (4NQO), weakly oncogenic 3-methyI-4-nitroquinoIine 1-oxide (3-methyI-4NQO), and the non-oncogenic 3-nitroquinoIine 1-oxide (3NQO) and 8-nitroquinoIine 1-oxide (8NQO). The detection of subtle alterations in DNA sedimentation velocity was greatly improved by a double-label procedure. Cells treated for 2 hours with the various nitroquinoIine N-oxide compounds were prelabelled with 0.05 uCi/ml ¹⁴C-thymidine for 24 hours. Untreated control cells were labelled with 0.25 uCi/ml ³H-thymidine for 24 hours. Aliquots of quinoline N-oxide treated and untreated cells were mixed, layered on the alkaline sucrose gradient, centrifuged at 25,000 rpm for 300 minutes, and the amount of ¹⁴C (treated) and ³H(untreated) radioactivity in each fraction of the gradient was determined. The alkaline sucrose gradient technique was modified in the following ways: (1) a PBS cell suspension was layered directly onto a 2% sucrose solution overlay, on the gradient, to reduce DNA-shearing forces believed previously encountered with a 0.5M NaOH overlay, (2) cell lysis and centrifugation were carried out at 4° rather than room temperature, and (3) the number of cells layered per gradient was reduced to 12,000. A correlation between the degree of oncogenicity of nitroquinoline N-oxides and their capacity to induce DNA single-strand breakage was indicated, although limited because of the low sensitivity of the sucrose gradient technique. Single-strand breaks of DNA occurred when celIs were treated for 2 hours with 5x10⁻⁶M 4NQO but were not detectable when exposed to 4NQO at a 1x10⁻⁶M concentration or less. However, when cells were treated with the weakly oncogenic 3-methyI-4NQO (5x10⁻⁶M) or the non-oncogenic 3NQO and 8NQO (5x10⁻⁶M) there were either no singIe-strand breaks produced or the frequency was too small to be recognized. The repair of single-strand breaks was measured by sampling 4NQO-exposed cells after various periods post-treatment and estimating the amount of ¹⁴C(treated)-DNA (in percent of total ¹⁴C counts) over and above the amount of ³H(untreated)-DNA (in percent of total ³H counts) occurring in the top half of each gradient. Substantial repair at 24 hours was indicated by less than 4% ¹⁴C-DNA above ³H-DNA as opposed to 29% ¹⁴C-DNA above ³H-DNA at 0 hours post-treatment incubation. Caffeine (1,3,7-trimethyIxanthine), added at a concentration of 4x10⁻³M to cell cultures, greatly reduced DNA single-strand breaks induced by 4NQO (4x10⁻⁶M). Attempts were made to correlate the capacity of synthetic quinoline N-oxides to induce DNA single-strand breaks with their capacity to invoke charge-transfer complexes with one or more DNA nucleotides, and so this study suggests approaches by which biological phenomena can be interpreted, ultimately, in terms of relative electron charge densities of molecules. / Medicine, Faculty of / Medical Genetics, Department of / Graduate

Chromans and quinolines can be found in the core structures of many biologically active natural products. Recognizing new and efficient ways to synthesize these useful compounds is vital to modern drug design. Calyxin I, Calyxin J and Epicalyxin J are three natural products that have been shown to have antiproliferative activity against two cancer cell lines. The core tetrahydropyranochromene ring system that is common among all three compounds was synthesized. The preferred diastereomer in this synthesis was the syn conformer, which was confirmed by a 2-D NOESY experiment. Theoretical MP2 calculations showed that a favorable pi-pi stacking interaction could be responsible for the diastereoselectivity. A two-step synthesis of tetrahydro-2Hurochromenones was achieved. This synthesis involved the cyclopropanation of 2H-chromenes using diazo compounds or iodonium ylides and a rhodium catalyst. In the presence of a Lewis acid, the cyclopropane intermediate underwent acid-catalyzed rearrangement to a gamma-lactone. The stereochemistry of the lactones was based on X-ray crystallography. Lactonization of 2H-chromenes could be important in the construction of larger flavonoids or biflavonoids in the future. 4-Arylquinolines and 2,4-diarylquinolines were produced using a [4+2] cycloaddition reaction as the key step in their synthesis. An array of N-aryl and N-protected 1-azadienes were constructed from their corresponding cinnamaldehydes or chalcones. A 1,4-dihydroquinoline cycloadduct was prepared from a [4+2] cycloaddition reaction of a 1-azadiene with benzyne. Among the N-protected cycloadducts, the N-tosyl derivatives were used to generate various quinolines. Also, a short synthesis of 3-O-methylviridicatin from one of the N-tosyl cycloadducts is presented.

No description available.

Aromatic oligoamide foldamers possess a high potential for mimicking the secondary structures of biopolymers. These oligomers are efficiently designed, easy to synthesize, and allow one to reach a wide range of stable folded states.Thus far, we want to utilize stable states of these oligomers and a variety of groove binding agents combining together , and then study their influence on DNA.

Aromatic oligoamide foldamers has high potential to mimic the secondary structures of biopolymers. These oligomers by using intramolecular hydrogen bonds and £k-£k interaction of aromatic rings to form a stable foldamer. We use the helical form of these oligomers and combine to the groove binding agents, then study the influence on DNA .

Thesis (M.S.)--University of North Carolina Wilmington, 2009. / Title from PDF title page (February 16, 2010) Includes bibliographical references (p. 66-67)

No description available.