| EPSRC Reference: |
GR/M72647/01 |
| Title: |
THE SYNTHESIS OF CHLORINATED NATURAL PRODUCTS AND THE IDENTIFICATION OF SUBSTRATES FOR CHLORINATING ENZYMES |
| Principal Investigator: |
Willis, Professor C |
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| Department: |
Chemistry |
| Organisation: |
University of Bristol |
| Scheme: |
Standard Research (Pre-FEC) |
| Starts: |
01 October 1999 |
Ends: |
30 September 2002 |
Value (£): |
83,097
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| EPSRC Research Topic Classifications: |
| Biological & Medicinal Chem. |
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| EPSRC Industrial Sector Classifications: |
| Chemicals |
Pharmaceuticals and Biotechnology |
| No relevance to Underpinning Sectors |
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Summary on Grant Application Form |
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The syntheis of barbamide and a dichlorinated analogue will be explored via coupling of N-methyl-dolaphenine and a trichlorinated C1-C6 fragment. A key stage will be the development of an efficient route to S-3-trichloromethyl and S-3-dichloromethylbutanoic acids which are themselves versatile building blocks to a range of di- and trichlorinated natural products. Various methods are proposed using organometallic reagents and radical reactions to give a flexible approach which may be simply adapted for the incorporation of carbon-13. The synthetic compounds will be compared with metabolites in extracts from L Majuscula.A series of carbon-13 labelled putatuve biosynthetic intermediates will be prepared and fed to L. Majuscula to establish the key chlorination step on the biosynthetic pathway and to gain an insight into the substrate specificity of the chlorinating enzyme(s).We propose that the trichlorination process proceeds by sequential chlorination of the methyl group via the mono- and dichlorinated species (with L-leucine as a likely enzyme substrate). Once the substrate for the chlorinating enzyme(s) has been established, this hypothesis will be tested by synthesis of the putative carbon-13 labelled mono- and dichlorinated intermediates and feeding studies to a cell free preparation from L. Majuscula with chlorinase activity.
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Key Findings |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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Potential use in non-academic contexts |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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Impacts |
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| Description |
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk |
| Summary |
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Sectors submitted by the Researcher |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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| Project URL: |
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| Further Information: |
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| Organisation Website: |
http://www.bris.ac.uk |