title: 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 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.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Shi
authors.forename: Georg
authors.initials: G
authors.lastname: Manolikakes
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Yeh
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Guerrero
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Shenvi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shigehisa
authors.forename: Phil S
authors.initials: PS
authors.lastname: Baran
mesh_terms: D002478:Cells, Cultured; D006801:Humans; D011083:Polycyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D011083:Polycyclic Compounds; C531521:cortistatin A