Synfacts 2009(4): 0353-0353  
DOI: 10.1055/s-0028-1088085
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of (+)-Cortistatin A

Contributor(s): Philip Kocienski, Indu Dager
K. C. Nicolaou*, Y.-P. Sun, X.-S. Peng, D. Polet, D. Y.-K. Chen*
Agency for Science, Technology, and Research, Singapore; The Scripps Research Institute, La Jolla and University of California, San Diego, USA
Further Information

Publication History

Publication Date:
23 March 2009 (online)

Significance

(+)-Cortistatin A is a potent anti-angiogenic agent that displays very high antiproliferative activity against human umbilical vein endo-thelial cells (HUVECs, IC50 = 1.8 nM) without showing any toxicity. It also demonstrates an excellent selectivity index (>3000) against HUVECs in comparison to their activity towards normal human dermal fibroplasts (NHDF) and several tumor cells (KB3-1, K562 and Neuro 2A). Based upon a modular strategy, this synthesis features a cascade sequence involving 1,4-addition/aldol condensation to construct dienone I.