| EPSRC Reference: |
GR/R07516/01 |
| Title: |
The Total Synthesis of Antascomicin A |
| Principal Investigator: |
Ley, Professor S |
| Other Investigators: |
|
| Researcher Co-Investigators: |
|
| Project Partners: |
|
| Department: |
Chemistry |
| Organisation: |
University of Cambridge |
| Scheme: |
Standard Research (Pre-FEC) |
| Starts: |
01 March 2001 |
Ends: |
29 February 2004 |
Value (£): |
175,806
|
| EPSRC Research Topic Classifications: |
| Biological & Medicinal Chem. |
Chemical Synthetic Methodology |
|
| EPSRC Industrial Sector Classifications: |
| No relevance to Underpinning Sectors |
|
|
| Related Grants: |
|
| Panel History: |
|
|
Summary on Grant Application Form |
|
Antascomicin A is an enticing yet intimidating target for the synthetic organic chemist with a complex polyketide structure including both lactone and lactam functionalities, 10 stereogenic centres, and a masked 1,2,3-tricarbonly unit. The Antascomicins bear structural similarities to both Rapamycin and FK-506 particularly in the C12 -C34 FKBP12 binding domain, which is reflected in their potent FKBP12 binding ability. This is a prerequisite for immunosuppressive activity, although the Antascomicin series do not function as immunosuppressants and have been shown to antagonise the effects of Rapamycin and Fk-506. These novel and architecturally complex compounds were isolated from the fermentation broth of a strain of Micromonospora, discovered in a soil sample collected in China. Non-immunosuppressive FKBP12 ligands have been shown to promote nerve re-growth in vitro and in vivo, and have been considered as neuroregenerative drugs. The total synthesis of Antascomicin A requires the development of novel synthetic methodology in order to construct its many challenging features, and would provide derivatives unavailable via natural resources to enable the exploration of the biological profile and structure-activity relationships within the Antascomicin family.
|
|
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.cam.ac.uk |