Subscribe to RSS
DOI: 10.1055/s-0029-1216673
Synthesis of (+)-Cortistatin A
Contributor(s):Philip Kocienski, Arndt W. SchmidtHarvard University, Cambridge, USA
Enantioselective Synthesis of (+)-Cortistatin A, a Potent and Selective Inhibitor of Endothelial Cell Proliferation
J. Am. Chem. Soc. 2008, 130: 16864-16866
Publication History
Publication Date:
25 May 2009 (online)
Key words
cortistatin A - aza-Prins cyclization -
![](https://www.thieme-connect.de/media/synfacts/200906/k052_s1.gif)
Significance
Cortistatin A was isolated together with structurally related molecules from the sponge Corticium simplex. It shows potent anti-angiogenetic activity with a high selectivity towards several human and murine cancer cell lines. The focal step of the synthesis is a highly stereoselective aza-Prins cyclization to complete the steroid-like carbon framework (G → H).
Comment
Thermal loss of bromide from C and cyclopropyl opening followed by fluoride-induced desilylation of the resulting pentadienyl cation leads to vinyl bromide D. Using the less electrophilic TMS group gave a cycloheptadiene via deprotonation at C6 by fluoride. Hydrogenation of the C16/C17 double bond in I could only be achieved in low yield using diimide generated from J.
![](https://www.thieme-connect.de/media/synfacts/200906/k052_s1.gif)