Abstract
This thesis is divided into three sections. Chapter 1 describes the kinetics of exchange of tritium from labelled diethyl malonate and sodium acetate. The rate of detritiation of diethyl malonate has been measured as a function of the base strength of the catalyst; the reaction was not catalysed by acids. Labelled sodium acetate was found to be stable in both acid and alkali solutions and no detritiation could be detected over the course of 6 days, In chapter 2, the application of tritium nuclear magnetic resonance spectroscopy to the determination of the position and distribution of the labelled atoms in tritiated organic compounds, has been reported. The compounds were prepared by base catalysed homogeneous exchange in solution using tritiated water as a source of label, A direct correlation between triton and proton chemical shifts was observed, thus enabling the predic- tion and assignment of [3]H n.m.r. spectra by reference to the large compilations of proton chemical shifts available in the literature. Chapter 3 describes the first successful application of [3]H n.m.r. spectroscopy to the elucidation of the biosynthesis of penicillic acid, a metabolite of Penici-Ilium cyclopium. The distribution of tritium obtained from the incorporation of acetate-T, showed stereospecific labelling of the C-5 methylene protons of penicillic acid, This observation suggests that the known inter- mediate orsellinic acid, undergoes 4,5 cleavage of the aromatic ring, A direct demonstration of this has also been made using [3,5-T]orsellinic acid. The extent of detritiation during biosynthesis of penicillic acid from acetate-T has been determined by an isotope tracer technique employing doubly labelled acetate ([14]CH[2]TCOO[-]) It has been inferred from the pattern of labelling obtai ned when using malonate-T, that the biosynthesis of penicillic acid involves condensation of 1 acetate unit with 3 malonate units, since no labelling of C-7 methyl protons was observed, A biosynthetic mechanism involving an oxepin intermediate has been proposed, which is consi stent with these findings. Finally in an appendix some aspects of the radiation safety in handling high levels of tritium have been described.