| EPSRC Reference: |
GR/R86140/01 |
| Title: |
enantioselective organoiron / heterocycloaddition approach to hippeastrine |
| Principal Investigator: |
Stephenson, Professor G |
| Other Investigators: |
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| Researcher Co-Investigators: |
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| Project Partners: |
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| Department: |
Chemistry |
| Organisation: |
University of East Anglia |
| Scheme: |
Standard Research (Pre-FEC) |
| Starts: |
01 March 2003 |
Ends: |
31 March 2006 |
Value (£): |
82,497
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| EPSRC Research Topic Classifications: |
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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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This project will use a combination of stereoselective procedures to address the synthesis of the anticancer alkaloid hippeastrine, starting from controlled access to chiral organoiron electrophiles, then using organoiron/organocuprate chemistry and a heterocycloaddition approach to complete the stereochemistry in the C ring, and a ruthenium-mediated reaction to close the D ring. The first objective is to relay chirality from correctly substituted electrophiles that carry all the functionality needed to complete hippeastrine, exploiting the 100% trans diastereoselectivity of nucleophile addition to cyclohexadienyliron(1+) complexes. The main synthetic challenge is the run of four adjacent chiral centres in the C ring at the B-C-D ring fusions. The development of novel combinations of bond-forming chemistries to address this set of chiral centres is the main feature of this proposal. Organoiron chemistry controls the construction of the central pair of chiral centres in the BC ring system, and a novel in situ heterocycloaddition trap using a nitroso derivative in the presence of trimethylamine N-oxide will provide the outer pair of chiral centres. This combination of synthetic procedures provides a short and unusual route to a class of natural products of interest to the pharmaceutical industry. The end-game of the synthesis will employ ruthenium-mediated intramolecular amination, or alternatives based on a modified Mitsinobu reaction, or reductive amination.
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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.uea.ac.uk |