Synthesis of cortistatins A, J, K and L

Abstract

The cortistatins are a recently identified class of marine natural products characterized by an unusual steroidal skeleton, which have been found to inhibit differentially the proliferation of various mammalian cells in culture by an unknown mechanism. We describe a comprehensive route for the synthesis of cortistatins from a common precursor, which in turn is assembled from two fragments of similar structural complexity. Cortistatins A and J, and for the first time K and L, have been synthesized in parallel processes from like intermediates prepared from a single compound. With the identification of facile laboratory transformations linking intermediates in the cortistatin L synthetic series with corresponding intermediates to cortistatins A and J, we have been led to speculate that somewhat related paths might occur in nature, offering potential sequencing and chemical detail for cortistatin biosynthetic pathways. The cortistatins have attracted a lot of attention in the synthetic community because of their interesting biological activity. Here, four of the cortistatin family are prepared from a common precursor. This efficient synthesis will assist in an investigation of structure–activity relationships and understanding of the biosynthetic route to these compounds.

Cite this article

Flyer, A., Si, C. & Myers, A. Synthesis of cortistatins A, J, K and L. Nature Chem 2, 886–892 (2010). https://doi.org/10.1038/nchem.794

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