This thesis begins with an introduction to inflammation and current antiinflammatory drugs in general, and the new small molecule somatotaxins developed by Fox and colleagues in particular. Chapter 1 describes the evidence used to propose the existence of structurally similar C-terminal lactam peptides that could potentially provide a novel anti-inflammatory pathway in vitro. Chapter 2 describes the synthesis of some C-terminal lactam peptides using solution phase peptide synthesis. Both linear and block syntheses were used. This chapter also describes some of the problems encountered using peptide coupling agents and our attempts to overcome them. Chapter 3 describes our investigations into thioacids for the block synthesis of peptides. The use of isoleucine in model peptides for the quantification of epimerization at the C-terminal amino-acid is also illustrated, and a series of NMR experiments were performed to allow us to differentiate between the relative stereoisomers of isoleucine residues in compounds. Chapter 4 describes the use of these 1H NMR experiments to predict the relative stereochemistry of a C-terminal isoleucine residue in the natural product, azolemycin A. The first total synthesis of azolemycins A and B, and a number of analogues, is then described.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:635583 |
| Date | January 2014 |
| Creators | Anderson, Zoe |
| Publisher | University of Warwick |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://wrap.warwick.ac.uk/65658/ |
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