| EPSRC Reference: |
EP/H015078/1 |
| Title: |
Development of An Asymmetric Radical Cyclisation and Application in the Synthesis of Nakadomarin A |
| Principal Investigator: |
Stockman, Professor RA |
| 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 Nottingham |
| Scheme: |
Standard Research |
| Starts: |
01 January 2010 |
Ends: |
30 September 2013 |
Value (£): |
285,439
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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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| Related Grants: |
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| Panel History: |
| Panel Date | Panel Name | Outcome |
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01 Oct 2009
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Physical Sciences Panel - Chemistry
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Announced
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Summary on Grant Application Form |
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The manzamine-related natural product Nakadomarin A was isolated from an Amphimedon sponge sp. (SS-264), and its extraordinary structure was determined by extensive NMR and mass spectral studies and published in 1997. The structure has a remarkable and unprecedented 8/5/5/5/15/6 hexacyclic framework with three contiguous stereogenic centres including one quaternary centre, and, unusually for a natural product, and uniquely for one of the manzamine alkaloids, a furan. It was found to exhibit cytotoxicity against murine lymphoma L1210 cells (IC50 1.3 ug/mL), inhibitory activity against cyclin dependent kinase 4 (IC50 9.9 ug/mL), and antimicrobial activity against a fungus and a Gram-positive bacterium. Furthermore, there is limited availability of this fascinating compound from Nature - just 6 mg were isolated from 1 Kg of sponge. In this project we will develop a highly innovative strategy for the formation of this molecule by developing a highly stereoselective radical cyclisation methodology and using the versatile and highly effective stereodirecting nature of the sulfinyl amine group to direct conjugate addition, alkylation and radical cyclisation. This bespoke methodology will also be fully generalised such that an outstanding and simple method for the formation of chiral cyclic amines will be available to the wider synthetic community.
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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.nottingham.ac.uk |