No description available.

No description available.

No description available.

No description available.

This thesis describes the reactions of some highly fluorinated aromatic and heteroaromatic compounds, in particular derivatives of naphthalene, quinoline and isoquinoline. Chapter 1 provides a general introduction to the preparation, reactions and applications of fluorine containing organic materials. Chapter 2 describes the reactions of some quinoline- and isoquinoline- thiolates with dimethyl acetylenedicarboxylate in an attempt to form six membered heterocycles. Chapter 3 describes nucleophilic substitution reactions of heptafluoro- quinoline and -isoquinoline with sulphur and oxygen nucleophiles. The sulphur nucleophiles are found to attack the 6- site in the isoquinoline and the 4- site in the quinoline. The oxygen nucleophiles attack the 1- site in the isoquinoline and 2- and 4- sites in the quinoline. Chapter 4 describes competition experiments of heptafluoro-quinoline and -isoquinoline with nucleophiles. Relative rates of attack at the 1- position and 6- position in the isoquinoline are determined for a variety of nucleophiles. The relative rates of two nucleophiles are determined for 4- attack in the quinoline. The relative reactivities of the two heterocycles are determined for two different nucleophiles. Chapter 5 describes the pyrolysis of heptafluoro-2-naphtiiyl propynoate which yield two difluoro-butenone derivatives. These decarbonylate under further pyrolysis to yield a 1,1-difluorocyclopropene. All the products were identified by X-ray crystallography. Chapter 6 gives experimental details for Chapter 2 to Chapter 5.

The work described in the dissertation is concerned mainly with organo-tin chemistry. In the first part, I describe the investigation of the stereochemistry of intramolecular electrophilic attack on a tin-carbon bond. The react ion of a number of cS - and � -s tanny 1 a lcoho 1 s and 0-stannyl acid chlorides was investigated, but stereochemical information was obtained only with the reaction of a 0-stannyl aldehyde to give a cyclopentanol, which proceeded largely with retention of configuration at the tin-bearing carbon, unlike the reaction of cS -stannyl alcohols, which give cyclopropanes with inversion. The second piece of work is a regio- and stereo-specific synthesis of allyl stannanes. s-stannyl ester enolates were treated with aldehydes to give alcol products with fairly good stereoselectivity: (~) and (~) enolates gave major products with different aldol relative stereochemistry. These aldols could be converted to s - hydroxy acids, then treatment with d imethy 1 formamide dimethyl acetal gave allyl stannanes stereospecifically, where steric and reactivity effects allowed. Thirdly, an investigation of the reaction of a tin cuprate with allenes is described. The cuprate reacts with 1,1-dimethyl allene followed by aqueous work up to give an allyl stannane, or the intermediate copper species can be quenched with a number of different ele,ctrophiles to give further substituted allyl stannanes. Similarly, allene itself reacts to give either vinyl or allyl stannanes, depending on the conditions used. Unfortunately, the factors governing the regiochemistry of the reaction with allene are not yet fully understood, and mixtu r es of products often result. Finally, I describe efforts to perform a kinetic resolution of a racemic Grignard reagent in which the chiral centre is the meta 1-bear ing carbon. It was hoped that react ion of the Gr ignard with half an equivalent of an optically active carbonyl compound would leave the remaining Gr ignard partially reso 1 ved. However, this did not prove to be successful.

No description available.

La circulation des cellules, du sang vers les tissus, est guidée par des molécules exprimées spécifiquement au niveau des cellules endothéliales constituant les vaisseaux sanguins. Les molécules conférant la spécificité de la localisation sont différentes selon l'organe et le microenvironnement considérés. A partir de lignées endothéliales spécifiques d'organes, les études menées sur le rôle des chimiokines et de leurs récepteurs dans la spécificité de l'endothélium ont montré que l'activité biologique de certaines chimiokines est restrictive à une lignée endothéliale en terme de recrutement des lymphocytes et par leur capacité à augmenter la formation de vaisseaux sanguins (angiogénèse) in vitro. De plus, notre modèle d'inflammation cutanée basé sur les cellules endothéliales de la peau, a permis des études plus appliquées mettant en évidence des molécules anti-inflammatoires vis-à-vis de l'endothélium de la peau en collaboration avec la Société BioEurope du groupe Solabia.

Nature has evolved the ability to form a C-F bond, as exemplified by the bacterium Streptomyces cattleya, which elaborates fluoroacetate (FAc) and 4-fluorothreomne (4- FT). The mechanism of this bond formation are unknown. This thesis probes the biosynthesis of fluoroacetate and 4-fiuorothreonine and in doing so explores the C-F bond forming process. Feeding stable isotope enriched primary metabolites to S. cattleya, followed by (^19)F NMR and GCMS analysis of the resultant fluorometabolites, highlights the role of the glycolytic pathway in delivering a substrate for fluorination. 3-Fluoro-l- hydroxypropan-2-one was synthesised and feeding studies eliminate this as the initial product of fluorination. Fluoroacetaldehyde was identified as a common fluorinated intermediate in the biosynthesis of both FAc and 4-FT. Whole cell studies demonstrate the rapid oxidation of fluoroacetaldehyde to FAc. 4-FT is produced in low quantities by S. cattleya incubated with fluoroacetaldehyde. The synthesis and feeding of [1-(^2)H]- fluoroacetaldehyde provide evidence that the resultant 4-FT is biosynthesised from fluoroacetaldehyde. The biotransformation from fluoroacetaldehyde to FAc was shown in cell free studies to be mediated by an aldehyde dehydrogenase, requiring NAD(^4) as a co-factor. The substrate specificity of fluoroacetaldehyde dehydrogenase was probed by spectrophotometrically monitoring the production of NADH in the presence of different aldehydes. Further cell free experiments probed the biosynthetic origins of fluoroacetaldehyde. Glycolaldehyde phosphate and various phosphorylated glycolytic intermediates were incubated with cell free extracts of S. cattleya and a plethora of co-factors. In the absence of observing fluorination activity, it was shown that the cell free extract acts to dephosphorylate the substrates. The putative role of glycolaldehyde phosphate was explored by feeding isotopically labelled glycolaldehydes to whole cells of the bacterium. The results were not consistent with direct conversion from glycolaldehyde phosphate to fluoroacetaldehyde.

The work described is an extension of the ligand-transfer reactions of substituted cyclobutadienes and cyclopentadienyls previously carried out by Maitlis et al. Efforts were directed particularly to ligand-­transfer reactions of n-allyl-transition metal complexes. The reactions of organic halides with metal carbonyls were also studied in attempts to isolate new organometallic derivatives. / Thesis / Master of Science (MS)