Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 131, Issue 30, Pages 10587-10597Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ja902939t
Keywords
-
Categories
Funding
- A*STAR, Singapore
Ask authors/readers for more resources
Total syntheses of the highly selective antiproliferative natural products cortistatins A (1) and J (5) in their naturally occurring enantiomeric forms are described. The modular and convergent strategy employed relies on an intramolecular oxa-Michael addition/aldol/dehydration cascade reaction to cast the ABCD ring framework of the molecule and both Sonogashira, and Suzuki-Miyaura coupling reactions to assemble the necessary building blocks into the required heptacyclic skeleton. A divergent approach from a late-stage epoxy ketone leads to both target molecules in a stereoselective manner. The developed synthetic technologies were applied to the construction of several analogues of the cortistatins which were biologically evaluated and compared to the natural products with regards to their antiproliferative activities against a variety of cancer cells. Analogues 8 and 81, lacking both the dimethylamino and hydroxyl groups of cortistatin A, were found to exhibit comparable biological activity as the parent compound, leading to the conclusion that such functionalities are not essential for biological activity.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available