The application of lipase mediated resolutions to the synthesis of the optical isomers of bufuralol and methadone
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 cytochro...
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University of Edinburgh
2000
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| Online Access: | http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.652705 |
| Summary: | 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. |
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