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This thesis focuses on the requirement for new methodologies to incorporate 11C into biologically active compounds for Positron Emission Tomography (PET). The use of PET has expanded over recent years as a valuable imaging technique for the study of drug delivery as well as the study of neurological diseases and oncology. The short half-life of 11C (20.4 min) limits its use to approximately 1 hour therefore rapid chemistry is required to radiolabel tracer molecules before use in vivo. Chapter 1 includes an overview of the literature in the areas of PET radiochemistry, transition metal-catalysed carbonylation, N-heterocyclic carbenes, hemilabile ligands, titanium and zirconium imido complexes and nickel-/palladium-catalysed carboxylations. Chapters 2 and 3 detail the investigations of a palladium-catalysed carbonylation reaction for the formation of amides commonly found in biologically active compounds. N-benzylbenzamide was synthesised in a model reaction which tested a range of diphosphine ligands and N-heterocyclic carbenes. The best performing systems were taken forward to be tested with [11C]CO in the radiochemistry laboratories at the GSK Clinical Imaging Centre at Hammersmith Hospital with excellent radiochemical purities of [11C]N-benzylbenzamide (99 %) and good radiochemical yields (55 %). Hemilabile phosphorus-thioether (P-S) and phosphorus-ether (P-O) bidentate ligands were also investigated in the synthesis of N-benzylbenzamide and compared to diphosphine ligands in this reaction and new palladium catalysts were prepared with novel P-S ligands. [11C]CO2 was examined as a potentially useful source of [11C] for radiolabelling as research into transition metal-mediated processes to activate CO2 for environmental reasons has grown in recent years. Chapter 4 investigates some recent literature detailing nickel- and palladium-catalysed carboxylation of organozinc halides in the synthesis of carboxylic acids. Titanium and zirconium imido complexes were synthesised with the intention of forming [11C]isocyanate precursors - this work is described in Chapter 5. A range of work has been carried out and potential future studies in all these areas are specified at the end of the thesis. |
