| EPSRC Reference: |
GR/M83803/01 |
| Title: |
SYNTHESIS OF HETEROCYCLIC PEPTIDE MACROCYCLES: MOROIDIN |
| Principal Investigator: |
Moody, Professor CJ |
| Other Investigators: |
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| Researcher Co-Investigators: |
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| Project Partners: |
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| Department: |
Chemistry |
| Organisation: |
University of Exeter |
| Scheme: |
Standard Research (Pre-FEC) |
| Starts: |
01 November 1999 |
Ends: |
31 October 2002 |
Value (£): |
167,167
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| EPSRC Research Topic Classifications: |
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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 synthesis of bioactive cyclic peptides is an area of current interest world-wide, since many naturally occurring macrocyclic peptides exhibit a wide range of biological effects. Moroidin is no exception and possesses potent biological activity. Microgram quantities of moroidin elicit powerful acetylcholine and/or 5-hydroxytryptamine like responses, and therefore moroidin is of biological significance as a biochemical tool in neurochemistry. It is proposed to develop a flexible route to moroidin based on the coupling of three fragments: two dipeptides (LeuVal and ArgGly) and a more complex highly modified leucine-tryptophan-histidine fragment. To synthesise the key indole core of moroidin it is proposed to develop the use of chiral oxime ethers in the asymmetric synthesis of unusual amino acids. This will provide the required beta- (6-indolyl) substituted leucine for subsequent incorporation of the histidine residue using the facile nucleophilic substitution of 2-chloroindole derivatives previously developed in our laboratory. The peptide fragments of moroidin will be approached using chemoselective N-H insertion reactions of rhodium carbenoids derived from diazophosphonates. To couple the various fragments together, we propose to develop a new use of the intramolecular Wadsworth Emmons reaction for the synthesis of peptide macrocycles, and also investigate some more adventurous transannular coupling reactions.
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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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Impacts |
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| Description |
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk |
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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.ex.ac.uk |