Synthetic methods of phosphinic acids and bicyclic aza-beta and gamma-lactams has been described.

Synthetic methods of phosphinic acids and bicyclic aza-beta and gamma-lactams has been described.

The aim of this work was studying of the coordination properties of TACN macrocyclic derivatives with aminophosphinate pendant arms. Two ligands were prepared, one with two pendant arms NODPam and one with three pendant arms NOTPam. Because of degradation of ligand NODPam during its synthesis, only the ligand NOTPam was studied further. Acid-base properties of ligand and termodynamic stability of aluminium and gallium complexes were studied. Formation and disociation studies were performed with the complexes. Coordination of fluoride ions to aluminium complex was studied using ion selective fluoride electrode. Finally coordination of complex AlFx with ligand NOTPam was studied using 19F and 27Al NMR spectroscopy. Selected experiments were made also with ligand NOTA. Key words: macrocyclic complexes, positron emission tomography, phosphinic acids

The syntheses and characterisation of di(cyclohexylmethyl), di(2-cyclohexylethyl), di(2-methylcyclohexyl) and di(4-methylcyclohexyl) phosphoric acids; cyclohexylmethyl phosphonic acid monocyclohexylmethyl ester, di(cyclohexylmethyl), di(4-methylcyclohexyl), di(4-tert- butylcyclohexyl), di(3-methylcyclohexyl), di(3,5-dimethylcyclohexy) and di(2-methylcyclohexyl) phosphinic acids are reported. Problems encountered and how they were resolved during the preparation of the above organophosphorus acids are reported and discussed in detail. These acids are then evaluated as potential hydrometallurgical extractants, for the separation of cobalt from nickel in acid leach liquors, and compared with two commercially available extractants, namely di(2-ethylhexyl)phosphoric acid (D2EHPA) and di(2,4-4- trimethylpentyl)phosphinic acid (Cyanex 272). The effects of variablest such as metal feed solution concentration, extractant concentration, diluent, modifier and temperature are examined experimentally in order to determine which factors are important for optimisation of an extraction system. The extraction characteristics for each acid as a function of pH are presented graphically and the pHO 5 values, distribution coefficients and separation factors are calculated. The dialkylphosphinic acids are found to exhibit much greater selectivity, for cobalt over nickel, than the dialkylphosphoric acids. It is postulated, that steric crowding of the phosphorus atom, by the hydrocarbon groups attached to the phosphorus, increases the selectivity of an extractant. This effect is particularly apparent in the dialkylphosphinic acids with di(2-methylcyclohexyl)phosphinic acid giving the best selectivity; much better than the commercially available Cyanex 272. Several of the dialkylphosphinic acids, evaluated as extractants in this thesis, are protected by a British Patent Application.

The syntheses and characterisation of di(cyclohexylmethyl), di(2-cyclohexylethyl), di(2-methylcyclohexyl) and di(4-methylcyclohexyl) phosphoric acids; cyclohexylmethyl phosphonic acid monocyclohexylmethyl ester, di(cyclohexylmethyl), di(4-methylcyclohexyl), di(4-tert- butylcyclohexyl), di(3-methylcyclohexyl), di(3,5-dimethylcyclohexy) and di(2-methylcyclohexyl) phosphinic acids are reported. Problems encountered and how they were resolved during the preparation of the above organophosphorus acids are reported and discussed in detail. These acids are then evaluated as potential hydrometallurgical extractants, for the separation of cobalt from nickel in acid leach liquors, and compared with two commercially available extractants, namely di(2-ethylhexyl)phosphoric acid (D2EHPA) and di(2,4-4- trimethylpentyl)phosphinic acid (Cyanex 272). The effects of variablest such as metal feed solution concentration, extractant concentration, diluent, modifier and temperature are examined experimentally in order to determine which factors are important for optimisation of an extraction system. The extraction characteristics for each acid as a function of pH are presented graphically and the pHO 5 values, distribution coefficients and separation factors are calculated. The dialkylphosphinic acids are found to exhibit much greater selectivity, for cobalt over nickel, than the dialkylphosphoric acids. It is postulated, that steric crowding of the phosphorus atom, by the hydrocarbon groups attached to the phosphorus, increases the selectivity of an extractant. This effect is particularly apparent in the dialkylphosphinic acids with di(2-methylcyclohexyl)phosphinic acid giving the best selectivity; much better than the commercially available Cyanex 272. Several of the dialkylphosphinic acids, evaluated as extractants in this thesis, are protected by a British Patent Application. / Science and Engineering Research Council

No description available.

Le glutamate est le principal neurotransmetteur excitateur du système nerveux central. Il est responsable de la majorité des transmissions synaptiques. En revanche, cet acide aminé naturel est aussi impliqué dans de nombreuses neuropathologies notamment en cas de surconcentration au niveau des synapses. Les récepteurs métabotropiques du glutamate, capables de moduler la transmission synaptique, constituent des cibles thérapeutiques prometteuses. Ces récepteurs sont divisés en trois groupes et notre laboratoire s’est focalisé sur ceux du groupe III et particulièrement le sous-type 4 qui présente des caractéristiques intéressantes dans le traitement symptomatique de la douleur et de la maladie de Parkinson. Le manque d’outils pharmacologiques de ce récepteur nous a poussé à synthétiser de nouveaux agonistes orthostériques à partir du composé référence, le LSP4-2022. Cette molécule est issue de nombreuses optimisations chimiques du (S)-PCEP provenant lui d’un screening virtuel. Durant ces trois années de doctorat, nous avons pu peaufiner la relation structure-activité autour du LSP4-2022 en synthétisant des nouveaux analogues fluorés et hétérocycliques. En parallèle, une seconde étude nous a permis d’attribuer la configuration des deux diastéréomères constituants tous les composés testés à ce jour / Glutamate is the major excitatory neurotransmitter in the central nervous system. It is responsible of the majority of synaptic transmissions. In contrast, this natural amino acid is also involved in numerous neuropathologies and particularly in case of glutamate overconcentration in the synapse. Metabotropic glutamate receptors, that can modulate synaptic transmission, thus constitute promising therapeutic targets. These receptors are divided in three groups and our laboratory has been focused in group III and especially subtypes 4 which own interested properties in symptomatic treatment of pain and Parkinson Disease. The lack of pharmacological tools targeting this receptor prompts us to synthesize novel orthosteric agonist from the hit compound LSP4-2022. This molecule was obtained after several chemical optimizations from (S)-PCEP discovered from virtual screening. During my Ph.D., we could refine the structure-activity relationship of LSP4-2022 synthesizing new fluorinated and heterocyclic derivatives. Besides, a second study was carried out to identify the configuration of the two diastereomers which form tested compounds