This thesis describes the application of lipase mediated kinetic resolutions in the synthesis of two biologically active and pharmaceutically important compounds :- Bufuralol has activity as a beta-blocker and recently it has become useful in metabolism studies as a substrate for a specific cytochrome P450 enzyme. Chapter three details how bufuralol, formerly marketed as a racemate, can be conveniently prepared in optically enriched form with a lipase resolution of a precursor as the key step. Methadone is currently used worldwide as a treatment in the maintenance of patients with addictions to opiates. It is mainly administered as a racemic mixture although the activity of the drug is due to the levorotatory isomer only. Levo-methadone can be efficiently prepared by employing a lipase in the resolution of 1-dimethylamino-2-propanol which is an inexpensive starting material for the synthesis of methadone. This is described in chapter four. Since both isomers of 1-dimethylamino-2-propanol are isolated from the resolution dextro-methadone may also be prepared and although it shows little or no activity itself, dextro-methadone may be converted in two steps to levo-α-acetylmethadol which is used in the U.S. as a longer acting alternative to methadone.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:652705 |
| Date | January 2000 |
| Creators | Hull, Jonathan David |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/15056 |
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