Synthesis of Alkaloids and Kinetic Studies with Diamine Oxidase

This thesis covers two main topics of research: (1) the use of 1-pyrroline and 1-piperideine aimed towards the synthesis of alkaloids and analogues; and (2) the inhibition of diamine oxidase. (1) The Use of 1-Pyrroline and 1-Piperideine aimed towards the Synthesis of Alkaloids and Analogues. 1-Pyrroline is an unstable oil but can be complexed with zinc iodide to form a stable solid. This complex can be reacted, as a source of 1-pyrroline, with a range of beta-ketoacids to give acylpyrrolidines in high yield. 1-Pyrroline was also found to form stable solid complexes with zinc chloride, zinc bromide and cadmium iodide. Attempts to use the zinc iodide complex as a source of 1-pyrroline in cycloaddition reactions proved unsuccessful. The complexation of 1-piperideine with zinc iodide also proved unsuccessful, though 1-piperideine was reacted with beta-ketoacids to form acylpiperidines. 1-Piperideine and piperidine have been used in the construction of quinolizidine and tetracyclic quinolizidine alkaloids. (2) The Inhibition of Diamine Oxidase. A range of cyclic diamines was synthesised and tested as inhibitors of diamine oxidase using a spectrophotometric assay. This is a peroxidase-coupled assay which monitors the production of hydrogen peroxide during diamine oxidation. Although many of the compounds synthesised lack a primary amino group they are substrate analogues and could bind well to the enzyme. The majority of the compounds synthesised, inhibited the diamine oxidase catalysed oxidation of cadaverine, and they were shown to be competitive inhibitors. A range of Ki values was obtained for the compounds tested