| EPSRC Reference: |
GR/L68414/01 |
| Title: |
SYNTHESIS OF NATURALLY OCCURING HETEROCYCLIC COMPOUNDS GLYCOTHIOHEXIDE AGLYCONE |
| Principal Investigator: |
Moody, Professor CJ |
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| Department: |
Chemistry |
| Organisation: |
University of Exeter |
| Scheme: |
Standard Research (Pre-FEC) |
| Starts: |
13 October 1997 |
Ends: |
12 October 2000 |
Value (£): |
143,565
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| EPSRC Research Topic Classifications: |
| Chemical Synthetic Methodology |
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| EPSRC Industrial Sector Classifications: |
| No relevance to Underpinning Sectors |
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Summary on Grant Application Form |
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The thiopeptide antibodies, exemplified by glycothiohexide, geninthiocin and related compounds, are a growing class of sulfur containing modified cyclic peptides that inhibit protein synthesis in Gram positive bacteria, and show activity against multiply resistant bacteria.It is proposed to develop routes to these biologically important compounds as exemplified by the synthesis of the glycothiohexide aglycone by the coupling of three fragments: a threonine containing thiazole, a 2, 3, 6-trithiazolylpyridine, and an indole bridged across the 3, 4-positions with a modified glutamate.To synthesise the thiazole rings, a new carbenoid based on method will be developed, based on highly chemoselective N-H insertion reactions. The pyridine unit will be accessed by a hetero Diels-Alder reaction using vinyl oximes as azadienes, a system ideal for the synthesis of polysubstituted pyridines. The diastereoselective addition of metallated diazoesters will be investigated as a route to hydroxy-amino acids, and in particular the modified glutamate residue necessary for incorporation into the indolic lactone unit of the natural product.Finally the various fragments will be coupled together using peptide coupling techniques.
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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.ex.ac.uk |