ORGN 713 |
| Gnidimacrin is a complex 1-alkyldaphnane diterpene, which has demonstrated exceptional cytotoxic activity against a variety of cancer cell lines. The cellular target of gnidimacrin appears to be Protein Kinase C (PKC), but further investigation into its mode of action have been hampered by low isolation yields. In order to further study the remarkable anticancer activity of this compound an efficient route towards the tricyclic core of gnidimacrin has been developed. A highly diastereoselective palladium-catalyzed enyne cyclization was used to establish the A-ring with a suitably functionalized C-1 appendage, which was then extended to include a masked α-hydroxy carboxylic acid as a precursor to gnidimacrin's C-ring orthoester. This route has provided access to advanced precursor of gnidimacrin incorporating its tricyclic core and much of its functionality. Nine out of the thirteen stereogenic centers that are present in the fourteen-carbon 5,7,6-tricyclic core of gnidimacrin have been established.
|
|
Total Synthesis, Materials, Molecular Recognition, Process R&D, and Physical Organic Chemistry
8:00 PM-10:00 PM, Wednesday, 13 September 2006 Moscone Center -- Hall D, Poster
Division of Organic Chemistry |
