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Synfacts 2008(11): 1127-1127
DOI: 10.1055/s-0028-1083411
DOI: 10.1055/s-0028-1083411
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag
Stuttgart ˙ New York
Synthesis of (+)-Cortistatin A
Contributor(s):Philip Kocienski, Indu DagerR. A. Shenvi, C. A. Guerrero, J. Shi, C.-C. Li, P. S. Baran*
The Scripps Research Institute, la jolla, USA
Synthesis of (+)-Cortistatin A
J. Am. Chem. Soc. 2008, 130: 7241-7243
The Scripps Research Institute, la jolla, USA
Synthesis of (+)-Cortistatin A
J. Am. Chem. Soc. 2008, 130: 7241-7243
Further Information
Publication History
Publication Date:
23 October 2008 (online)
Key words
cortistatin A - Mukaiyama hydration - remote functionalization
Significance
(+)-Cortistatin A inhibits the proliferation of human umbilical vein endothelial cells (HUVECs, IC50 = 1.8 nM) without showing any toxicity. This synthesis utilizes a novel hydroxyl-directed dibromination of a methyl group (C → D) using AcOBr generated in situ.
Comment
Dibromination was achieved by a SH2 reaction of the transient O-centered radical (C → J → K → D). A SmI2-mediated radical opening of the cyclopropane E led to the formation of a dienolate via intermediates L and M, which then reacted with TBCHD to give the α-bromoketone F.