Abstract
This thesis details three different projects. The first project describes the synthesis of tritium-labelled Dickerson's DNA dodecamer, 5'-CGCGAATTCGCG-3', using phosphite triester chemistry. Coupling of the or A5 or A6 2'-deoxyadenosine nucleosides was optimized with only five molar equivalents when using a novel manual apparatus. Tritiated 2'-deoxyadenosine phosphoramidites were prepared from halogenated precursors by catalytic reduction with tritium gas. The NMR spectra of the nucleosides and nucleotides were assigned. The second project describes bovine pancreatic phospholipase Az inhibition as studied by 3H NMR spectroscopy. An unsaturated amide substrate analogue inhibitor was synthesized and site-specifically tritium-labelled by the reduction of an alkene double bond in the inhibitor using tritium gas and Wilkinson's homogeneous catalyst. The chosen reduction method was identified from a range of deuteriation procedures conducted on a model system. The third and final project describes the structure of chromone-2-carboxylates as studied by NMR spectroscopic and X-ray crystallographic methods. Brominated sodium cromoglycate was synthesized for use as a substrate for tritium labelling. Its structure and that of its precursor were determined by X-ray crystallographic, NMR NOE difference and NMR spectroscopic analyses. The structure arrived at differs from that previously published. An 170 NMR spectroscopic investigation of carboxylate derivatised chromone-2-carboxylates in a range of solvents was also undertaken. 1H, and 13C and 17O NMR assignments are given. Oxygen-17 enrichment was achieved by acid-catalysed exchange or acyl chloride hydrolysis with [17O]water. Acid-catalysis gave the product with the endocyclic ?-pyrone oxygen selectively enriched. Isotopic enrichment allowed the acquisition of high quality NMR spectroscopic data of molecules under experimental conditions which were untenable at natural oxygen-17 abundance.