| EPSRC Reference: |
GR/T07466/01 |
| Title: |
Total Synthesis of Salinosporamide A |
| Principal Investigator: |
Lam, Professor HW |
| Other Investigators: |
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| Researcher Co-Investigators: |
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| Project Partners: |
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| Department: |
Sch of Chemistry |
| Organisation: |
University of Edinburgh |
| Scheme: |
First Grant Scheme Pre-FEC |
| Starts: |
15 September 2004 |
Ends: |
14 September 2007 |
Value (£): |
117,334
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| EPSRC Research Topic Classifications: |
| Chemical Synthetic Methodology |
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| EPSRC Industrial Sector Classifications: |
| Pharmaceuticals and Biotechnology |
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| Panel History: |
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Summary on Grant Application Form |
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Salinosporamide A is a natural product isolated from actinomycete bacteria which live in tropical and subtropical ocean sediments. It's structure contains a four-membered lactone fused to a five-membered lactam, a ring structure which is also seen in the related compound omuralide. Omuralide has been of interest as a highly specific inhibitor of the 20S proteosome, an abundant complex that is responsible for the fragmentation and removal of unwanted proteins from within cells. As a result, omuralide and it's precursor lactacystin have been used as tools for the study of protein biochemistry. Salinosporamide A is approximately 35 times more effective at proteosome inhibition, and also displays highly potent cytotoxicity against a range of tumour cell lines.The proposed research seeks to develop an efficient total synthesis of salinosporamide A. The synthesis will demonstrate the utility of recently developed catalytic enantioselective methodology for the assembly of the densely functionalised core structure. The brevity and modular nature of the synthesis should allow the production of significant quanities of the natural product, as well as ready access to a range of analogues which will be tested for their biological 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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| Date Materialised |
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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.ed.ac.uk |