Current questions concerning the safety of industrial chemicals requires that many substances be re-evaluated to quantify the significance of their environmental and occupational hazards. A large number of epoxides have been found mutagenic and carcinogenic. However, for many of these epoxides the stereochemical requirements are still undefined. After a general introduction into the toxicology of epoxides (Chapter 1), Chapter 2 reviews the general methods developed, and adopted in the syntheses of chiral epoxides and their precursors. In Chapter 3, the materials, methods and instruments used in this project are outlined. A new synthetic route to optically active epoxides is described in Chapter 4. The acid catalysed ketalisation of D-camphorquinone with racemic 1,2-diols is shown to afford a kinetic resolution from which one diastereoisomer is formed predominantly. This dioxolane was hydrolysed to yield an optically active diol or converted into an epoxide. A general route to chiral 1,2-diols is described. The reaction of the enantiomers of methyloxirane with biological nucleophiles (protected N-acetyl esters of amino-acids containing reactive nitrogens [ histidine imidazole nitrogens ] or sulphur [ cysteine ] and the amino ester of valine) is described in Chapter 5. This chapter determines the structure and stereochemistry of the products, along with enantio- selectivities and kinetic data. This data was used to ascertain the relative rates of nucleophilic attack upon the enantiomeric pairs. For ambifunctional nucleophiles identification of the preferred site of alkylation and the regioselectivity of nucleophilic attack was deduced. A method for deducing the enantioselectivity of nucleophilic groups in peptides using specifically deuterated epoxide racemates is described (Chapter 6). Product mixtures are determined by m.s. The use of this method to deduce enantioselectivities in peptides and proteins is outlined.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:304220 |
| Date | January 1984 |
| Creators | Ellis, Martin Keith |
| Publisher | University of Warwick |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://wrap.warwick.ac.uk/108753/ |
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