Chapter 1 provides a general introduction to organofluorine chemistry and focuses on recent developments in fluorination techniques. It also details how the C–F bond influences conformational and physiochemical properties of organic molecules. Chapter 2 highlights the biological role of the telomere, telomerase and quadruplex DNA in cells. It discusses the inhibition of telomerase with small molecules that stabilise quadruplex DNA as a treatment for cancer. An overview of the development of structurally related telomerase inhibitors and recent X-ray crystallographic structural data with BSU6039 and BRACO-19 telomeric DNA is presented. Chapter 3 discusses the synthesis of fluorinated BSU6039 analogues for the investigation of the conformational effects of fluorine in 5-membered rings and its influence on binding with quadruplex DNA. These compounds have been successfully co-crystallised with telomeric DNA and their relative stabilisation of telomeric DNA has been assessed. The latter half of this chapter focuses on the co-crystal structures between (S,S)- and (R,R)-144 with Oxytricha nova telomeric DNA, discussing the key differences between the two stereoisomers. Chapter 4 details the synthesis of fluorinated BRACO-19 analogues. The syntheses of such fluorinated analogues were achieved through a base mediated coupling between 3,6-diaminoacridone and an α-fluorinated-β-amino ester. The α-fluorinated-β-amino ester was synthesised through a deoxyfluorination-mediated approach, using the stereochemistry of natural amino acids. Chapter 5 describes the stereo- and regio- selectivity of deoxyfluorination reactions with dipeptides bearing the β-amino alcohol functionality. Understanding this selectivity enabled the development of a method towards α-fluorination of tertiary amides. The application of this fluorination method with an orthogonally protected tertiary amide is described.

In this dissertation, we discuss the development of new phase transfer agents, which are capable of rapid fluorination of silicon. These are 18-C-6 derivatives containing a hydroxyl group in the side arm (podand), also known as C-pivot lariats. The syntheses of these lariats including several that have not been previously reported and their efficient purification are described. The synthesis route leads to a robust and generalized approach to obtain these lariats on the gram scale. These agents were initially designed for applications in positron emission tomography (PET). In this medical imaging modality, tracer agents containing silicon have found promising utility as fluoride receptors for more rapid radiolabeling. Phase transfer agents are generally required for 18F-labeling due to the low solubility in organic reaction media and reactivity of cyclotron-generated [18F]potassium fluoride. We envisioned that 18-C-6 derivatives may serve as both phase transfer agents as well as nucleophilic catalysts (CENCs). In this conception, CENCs were rapidly pre-complexed with KF followed by silicon fluorination, which takes advantage of a previously established silicon dianion mechanism. In collaboration with researchers at the NIH, we studied the effect of various linkers connecting the metal chelating unit to the nucleophilic hydroxyl group on the radiofluorination of silicon under mild condition. A hydrolysis resistant aryl silicon fragment has also been developed that contains various functional groups for convenient attachment to the potential PET radiotracer agents. In a second project, we demonstrate the unique reactivity of γ-silyl allenyl esters. Taking advantage of the silyl group as a fluoride acceptor, these allenoates readily underwent addition to a variety of carbon electrophiles, including aryl fluorides, to afford all-carbon quaternary centers bearing an ethynyl group. Surprisingly, in the presence of aldehydes, exclusive bis-substitution occurs at the γ-position to afford the dicarbinol. Details relating to reaction optimization and substrate scope for both the reactions are presented. Dicarbinol allenes were subsequently converted to highly substituted δ-lactones, a novel 6-hydro-2-pyrone as single diastereomers. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2018. / FAU Electronic Theses and Dissertations Collection

Ce travail porte sur la synthèse et la caractérisation de fluorures divisés obtenus par voiesolvothermale assistée par chauffage micro-ondes pour la réduction des impuretés dans lecycle du combustible nucléaire. / This work deals with the synthesis and characterization of divided fluorides obtained bysolvothermal process assisted by microwave heating to reduce impurities in the nuclear fuelcycle.

La tomographie par émission de positons (TEP) est une technique d'imagerie médicale largement utilisée en oncologie. Cette technique peut, par exemple, fournir des informations sur la localisation de tumeurs dans le corps humain, et le développement de nouvelles méthodes pour la production automatisée de radiotraceurs spécifiques reste un domaine d’actualité. Dans ce contexte, un nouveau type de précurseurs silylés pouvant être fluorés en dernière étape a été développé. La fluoration de ce nouveau motif imidazole-silylé par du [19F]F- puis par du [18F]F- a été validée sur différents bioconjugués. Le greffage de ce motif a ensuite été testé selon plusieurs méthodes. En particulier, une des voies de synthèse a pu montrer que la fluoration de bioconjugués portant ce motif et greffés sur une résine était possible au [19F]F-. Enfin, le produit radiomarqué au [18F]F- a pu être détecté au cours d’essais préliminaires, permettant ainsi de valider la stratégie choisie. / Positron Emission Tomography (PET) is a medical imaging technique widely used in oncology. For example, this technique can provide information on the localization of growing tumors in the human body, and the development of news methods for the automated production of specific radiotracers is still required. In this context, a new silylated precursor, which can be fluorinated in the last step, has been developed. The fluorination of this new imidazole-silylated unit with [19F]F- and with [18F]F- has been validated on various bioconjugates. The grafting of this moiety has been tested following different strategies. In particular, one of the synthetic pathway showed that the fluorination of bioconjugates with resin grafted moiety was possible with [19F]F-. Finally, the [18F] radiolabeled product was observed during preliminary [18F]F- fluorination experiments, thus validating the chosen strategy.

The development of a synthetic method of radiolabelled methylphosphono-fluoridates on a milligram scale is presented. The aim of this method is, besides affording high yield, to choose reaction pathways and reagents so that handling and transfer of labelled toxic substances is minimised, thereby reducing the risk of exposure as much as possible. The only substituent that is stable enough to be labelled is the methyl group, directly bonded to phosphorus. A drawback when labelling the methyl group is that it requires the label to be introduced early in the synthesis since the carbon-phosphorus bond of the methyl substituent usually has to be synthesized a few steps ahead of the final product. Two new classes of reagents for halogenation of phosphorus oxyacids have been developed. Firstly, four different analogues of α-chloroenamines and α-fluoroenamines were evaluated. Secondly, cyanuric fluoride was assessed in solution, but more importantly, as a resin-bound reagent. The reagents are evaluated for halogenation of phosphinic, phosphonic and phosphoric acids. Cyanuric fluoride is also successfully loaded on a polystyrene resin and used as a solid-phase reagent. The reagents produce high yields and low levels of impurities on a milligram scale. Furthermore, a new method for the preparation of mono-alkylated phosphonic acids on a small scale has been developed. The new method utilises the crystal water bound to certain salts to liberate limited amounts of water in a controlled manner. Phosphonic dichlorides are in this way reacted with water to form anhydrides. The anhydride is then cleaved with an appropriate alcohol to produce mono-alkylated phosphonic acids. / Rikard Norlin = Rikard Wärme

The discovery of unique properties of graphene has led to the development of graphene for a variety of applications like integrated circuits, organic electronic devices, supercapacitors, sensors, and composite materials. Fluorination of graphene enables control of its physical, chemical, and electronic properties. Our initial studies demonstrated the viability of sulfur hexafluoride plasmas to fluorinate epitaxial graphene as a safer alternative to the commonly reported techniques of fluorination that include exposures to fluorine and xenon difluoride gas. Formation of carbon-fluorine bonds after SF6 plasma-treatment was confirmed by x-ray photoelectron spectroscopy. Raman spectroscopy and low-energy electron diffraction studies suggest that the framework of sp2-hybridized carbon atoms remains intact after the plasma-treatment. Increase in work function after the fluorination was determined by ultra-violet photoelectron spectroscopy. The findings of our subsequent investigation to controllably modify the work function of epitaxial graphene via plasma-fluorination indicate that the work function of fluorinated epitaxial graphene is controlled by the polarity of carbon-fluorine bonds. Further studies to investigate the effect of the surface topography of epitaxial graphene on the work function of plasma-fluorinated epitaxial graphene were performed using scanning Kelvin probe microscopy (SKPM). The results of SKPM characterization of plasma-fluorinated epitaxial graphene demonstrated that the increase in the work function of epitaxial graphene after plasma-treatment is independent of its surface topography, but non-uniform fluorination may result from non-uniformities in plasma density.

The field of organic electronics has received much attention over the last few years, and engineering of organic crystals to grow with pi-electron systems arranged in a face-to-face motif has been shown to be beneficial in electronic devices. The effects of combining aromatic and perfluorinated aromatic derivatives have shown that the intramolecular stacking pattern can be changed from an edge-to-face arrangement to that of a face-to-face motif. Before the work described herein, there were no reported studies of the supramolecular behavior of fused polycyclic aromatic compounds with partial peripheral fluorination, inducing the desired face-to-face behavior. This is the main focus of the thesis. Furthermore, by exploiting the interactions between the fluorinated and non-fluorinated faces of the molecule, columnar liquid crystalline behavior can be achieved through variations of the alkyl substituents on the molecule.

京都大学 / 新制・課程博士 / 博士(エネルギー科学) / 甲第23999号 / エネ博第435号 / 新制||エネ||82(附属図書館) / 京都大学大学院エネルギー科学研究科エネルギー基礎科学専攻 / (主査)教授 野平 俊之, 教授 萩原 理加, 教授 宇田 哲也 / 学位規則第4条第1項該当 / Doctor of Energy Science / Kyoto University / DFAM

Thesis (Ph. D.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves 115-116). Also available in print.

Les déficiences en transporteur vésiculaire de l'acétylcholine (VAChT) sont l'un des symptômes précoces de perte neuronale lors de la maladie d'Alzheimer, perte fortement corrélée avec la gravité de la démence associée. Comme le (2R,3R)-5-IBVM est le radioligand de référence du VAChT utilisé en imagerie TEMP, la synthèse par fluoro-de-diazenation a conduit à son analogue fluoré, le 5-FBVM, ainsi qu’à ses énantiomères. Par étude 3D-QSAR, confirmée par évaluation in vitro, chaque énantiomère du 5-FBVM montre une affinité pour le VAChT similaire au 5-IBVM. D'autres travaux ont permis d'améliorer le rendement en 5- FBVM par fluoro-de-triazénation du précurseur triazène, le 5-TVB, en utilisant seulement de l’éthérate de trifluorure de bore qui joue le double rôle d’acide de Lewis et d’agent fluorant, dans le tétrachlorure de carbone, sous irradiation micro-onde. L’optimisation de la fluoro-detriazénation en étudiant différents paramètres expérimentaux compatibles avec un radiomarquage a permis d’obtenir le 5-[18F]FBVM. Ce résultat encourageant devrait conduire à l’obtention du 5-[18F]FBVM. / Deficiencies in vesicular acetylcholine transporter (VAChT) are among the earliest neuronal changes preceding clinical symptoms of Alzheimer's disease, and show a strong correlation with the severity of dementia. As (2R,3R)-5-IBVM is the lead and the only SPECT radioligand for VAChT human imaging, we synthesized by fluoro-de-diazoniation its fluoro analog 5-FBVM with corresponding enantiomers, and confirmed by 3D QSAR and in vitro studies that both enantiomers of 5-FBVM are of the same order affinity as 5-IBVM. Furthermore, we greatly improved 5-FBVM yield via fluoro-de-triazenation of the corresponding triazene precursor 5-TBV using boron trifluoride etherate under non-protic acid conditions in tetrachloromethane under optimized microwave irradiation. By testing different reaction parameters in numerous experimental attempts to find fluoro-de-triazenation conditions which can be transposed to radiofluorination, we may accomplished 5-[18F]FBVM. This encouraging result warrants to optimize 5-[18F]FBVM yield via promising methods obtained in cold chemistry.