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Scalable synthesis of cortistatin A and related structures.

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 ?(16)-alkene reduction with Raney Ni provided cortistatin A. With this scalable and practical route, copious quantities of cortistatinone, ?(16)-cortistatin A (the equipotent direct precursor to cortistatin A), and its related analogues were prepared for further biological studies.

SUBMITTER: Shi J

PROVIDER: S-EPMC3119343 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Scalable synthesis of cortistatin A and related structures.

Shi Jun J Manolikakes Georg G Yeh Chien-Hung CH Guerrero Carlos A CA Shenvi Ryan A RA Shigehisa Hiroki H Baran Phil S PS

Journal of the American Chemical Society 20110503 20

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 aff ...[more]

PMID: 21539314

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