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PMID: 21539314 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Scalable synthesis of cortistatin A and related structures.

Journal of the American Chemical Society ·Vol. 133 ·No. 20 ·2011-05-25 ·Pages 8014-27

Shi J, Manolikakes G, Yeh CH, Guerrero CA, Shenvi RA, Shigehisa H, Baran PS

Abstract

Full details are provided for an improved synthesis of cortistatin A and related structures as well as the underlying logic and evolution of strategy. The highly functionalized cortistatin A-ring embedded with a key heteroadamantane was synthesized by a simple and scalable five-step sequence. A chemoselective, tandem geminal dihalogenation of an unactivated methyl group, a reductive fragmentation/trapping/elimination of a bromocyclopropane, and a facile chemoselective etherification reaction afforded the cortistatin A core, dubbed "cortistatinone". A selective Δ(16)-alkene reduction with Raney Ni provided cortistatin A. With this scalable and practical route, copious quantities of cortistatinone, Δ(16)-cortistatin A (the equipotent direct precursor to cortistatin A), and its related analogues were prepared for further biological studies.

MeSH Terms
Cells, Cultured Humans Polycyclic Compounds/chemical synthesis,chemistry
Chemicals
Polycyclic Compounds cortistatin A
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Shi Jun
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Manolikakes Georg
Yeh Chien-Hung
Guerrero Carlos A
Shenvi Ryan A
Shigehisa Hiroki
Baran Phil S
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Article Info
Journal
Journal of the American Chemical Society
Abbr.
J Am Chem Soc
ISSN
1520-5126
DOI
10.1021/ja202103e
Published
2011-05-25
Epub
2011-00-03
Pages
8014-27
Language
English
Region
United States
NLM ID
7503056
PMCID
PMC3119343
Subset
IM
Grants
NCI NIH HHS · R01 CA134785 · United States
NCI NIH HHS · R01 CA134785-02 · United States
External Links
PubMed source DOI: 10.1021/ja202103e PMC Full Text View journal details
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