| EPSRC Reference: |
GR/S14429/01 |
| Title: |
Concise, Enanticocontrolled Synthesis of Luminacin D |
| Principal Investigator: |
Shipman, Professor M |
| Other Investigators: |
|
| Researcher Co-Investigators: |
|
| Project Partners: |
|
| Department: |
Chemistry |
| Organisation: |
University of Warwick |
| Scheme: |
Standard Research (Pre-FEC) |
| Starts: |
01 October 2003 |
Ends: |
30 September 2006 |
Value (£): |
104,394
|
| EPSRC Research Topic Classifications: |
| Biological & Medicinal Chem. |
Chemical Synthetic Methodology |
|
| EPSRC Industrial Sector Classifications: |
| Pharmaceuticals and Biotechnology |
No relevance to Underpinning Sectors |
|
| Related Grants: |
|
| Panel History: |
|
|
Summary on Grant Application Form |
|
This application deals with the total synthesis of luminacin D, a key member of a family of secondary metabolites isolated from Streptomyces sp. Mer-VD1207 which display potent anti-angiogenic activity (i.e. inhibit new blood capillary growth), appear to act by a unique mechanism of action, and may ultimately be of use in the treatment of a cancer and/or osteoporosis. Structurally, these natural products contain an epoxide ring as part of a rather unusual 1,5dioxaspiro[2.5]octane ring system. The principal aim is to develop new synthetic chemistry which will allow us to complete the first total synthesis of luminacir D. Specifically, we hope to devise an aldol/pyran assembly sequence which will establish the relative and absolute stereochemistry at 3 asymmetric centres and produce the pyran ring as well as a pivotal C-C bond in one-pot'. Completion of the total synthesis will enable us to unambiguously determine the C-2 stereochemistry of this natural product for the first time. Based on the fact that anti-angiogenic agents with diverse mechanisms of action possess an epoxide ring (e.g. fumagillin, eponemycin, rhizoxin), we speculate that the epoxide plays a key role in the biological function of luminacin D. Complex luminacir analogues will be made and screened for anti-angiogenic activity with a view to validating this hypothesis.
|
|
Key Findings |
|
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
|
|
Potential use in non-academic contexts |
|
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
|
|
Impacts |
|
| Description |
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk |
| Summary |
|
| Date Materialised |
|
|
|
|
Sectors submitted by the Researcher |
|
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
|
| Project URL: |
|
| Further Information: |
|
| Organisation Website: |
http://www.warwick.ac.uk |