The preparation of drug molecules is usually achieved by running a series of reactions one after the other. When the active ingredient of a drug is prepared, the first intermediate is prepared and isolated, and then taken on to a second step, where an additional conversion takes place. Several separate steps are used to prepare the final compound, and at each stage there is likely to be a loss of material as well as the lack of efficiency of this approach. However, Nature can create incredibly complex molecules within a single species - the anti-cancer drug Taxol is an example where the Yew tree makes a compound which is a formidable synthetic challenge to chemists in the laboratory. The taxol is naturally synthesised by a series of reactions which take place sequentially without the isolation of intermediates - a luxury that the laboratory chemist doesn't normally have available to them.By designing and developing flow reactors, this project will allow chemical reactions to be preformed without a conventional isolation procedure until the desired final structure has been prepared. The project will develop methods for allowing chemicals to react as they flow through pipes rather than in standard laboratory apparatus. As the reacting compounds flow through they will be converted into the next compound in the synthetic sequence, and then on to the next until the entire synthesis has been completed.One of the potential drawbacks of the continuous flow apparatus is that the individual reactions may require very different conditions from each other - very cold steps followed by hot steps, changes to the concentration of intermediates may be required, or even a change in solvent. These problems will be addressed by careful design of the reactor modules, and can involve microwave heating for example. We will develop continuous flow reactions for a series of organic reactions and then develop ways to couple the individual steps together. These coupled steps will then be developed to provide case study preparations of some well know pharmaceutical drugs. In particular, we will prepare Tamoxifen, which the leading drug for the treatment of breast cancer, as well as Effexor which a leading pharmaceutical for the treatment of depression, along with Benadryl (Nytol) which is a well-known anihistamine and sedative.
|Effective start/end date||1/07/09 → 16/05/13|
- Engineering and Physical Sciences Research Council
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