| EPSRC Reference: |
GR/N22489/01 |
| Title: |
NEW METHODS FOR THE ASSEMBLY OF 1-AZABICYCLO(3.1.0) HEXANES: APPLICATION TO THE SYNTHESIS OF FICELLOMYCIN |
| Principal Investigator: |
Shipman, Professor M |
| Other Investigators: |
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| Department: |
Chemistry |
| Organisation: |
University of Exeter |
| Scheme: |
Standard Research (Pre-FEC) |
| Starts: |
02 October 2000 |
Ends: |
01 October 2003 |
Value (£): |
73,116
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| EPSRC Research Topic Classifications: |
| Biological & Medicinal Chem. |
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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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Ficellomycin has been shown to inhibit the in vitro growth of gram positive bacteria and Staphylococcus aureus infections in mice. This antibiotic contains a number of unusual structural features, the most intriguing of which is the highly strained 1-azabicyclo(3.1.0)hexane ring system. To date, no work on the synthesis of ficellomycin has been described, hence efforts to make this target and elucidate its mechanism of action at the molecular level are very worthwhile scientific objectives. We envisage that the assembly of this relatively small natural product will nonetheless be stimulating and challenging. Our synthesis is centred around a stereocontrolled iminyl radical cyclisation onto a dehydroamino ester, derived from homochiral aspartic acid, and subsequent formation of the aziridine ring from the least hindered face of the resultant imine using ylid chemistry. Thus, in just two steps, we plan toto make both rings of the 1-azabicyclo(3.1.0)hexane and establish the relative and absolute stereochemistry found in ficellomycin. If time permits, we will explore the wider applications of this chemistry in organic synthesis. We plan to determine the antibiotic activity of a variety of synthetic and semi-synthetic materials, to establish whether it is the bicyclic ring system that is responsible for the observed antibiotic activity.
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Key Findings |
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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 |