| EPSRC Reference: |
GR/R56549/01 |
| Title: |
Serial Ring Closing Metathesis and Transannular Reactions: Total Synthesis of Adicipin and Trapoxin |
| Principal Investigator: |
Barrett, Professor T |
| Other Investigators: |
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| Project Partners: |
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| Department: |
Chemistry |
| Organisation: |
Imperial College London |
| Scheme: |
Standard Research (Pre-FEC) |
| Starts: |
01 February 2002 |
Ends: |
31 March 2005 |
Value (£): |
190,269
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| EPSRC Research Topic Classifications: |
| Biological & Medicinal Chem. |
Chemical Synthetic Methodology |
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| EPSRC Industrial Sector Classifications: |
| Pharmaceuticals and Biotechnology |
No relevance to Underpinning Sectors |
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Summary on Grant Application Form |
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There is a group of naturally occurring cyclic tetra-peptides that are endowed with significant biological activities including the antimalarial and coccidiostatic agent apicidin and trapoxin, a potent inhibitor of mammalian histone deacetylase. The principal investigator will examine the use of sequential alkene ring closing metathesis (RCM) and transannular reactions for the total syntheses of apicidin and trapoxin. RCM of an acyclic tetrapeptide diene should provide the macrocyclic tetrapeptide alkene. Subsequent transannular reaction involving amide nitrogen alkylation should produce the target cyclic tetrapeptide. Since the strategy in this approach involves the initial formation of 15-membered or larger macrocyclic arrays followed by a transannular ring contraction reaction, the approach is likely to be more efficient than classical approaches to the problematical 12-membered cyclic tetrapeptide skeleton. Additionally, there are considerable possibilities for variation of the cyclic tetrapeptide structures with change in the side chain residues and in the proline entity. Since the second ring unit is constructed late, there is considerable advantage in the elaboration of novel analogues. Success in this venture would provide concise routes to the bioactive natural products apicidin and trapoxin and general derivatives of the unusual cyclic tetrapeptide pharmacophore.
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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.imperial.ac.uk |