%0 Generic
%A Shi, Jun
%A Manolikakes, Georg
%A Yeh, Chien-Hung
%A Guerrero, Carlos A.
%A Shenvi, Ryan A.
%A Shigehisa, Hiroki
%A Baran, Phil S.
%D 2011
%T Scalable Synthesis of Cortistatin A and Related Structures
%U https://acs.figshare.com/articles/dataset/Scalable_Synthesis_of_Cortistatin_A_and_Related_Structures/2648611
%R 10.1021/ja202103e.s002
%2 https://ndownloader.figshare.com/files/4303141
%K chemoselective etherification reaction
%K Scalable Synthesis
%K unactivated methyl group
%K cortistatin
%K Raney Ni
%K Related StructuresFull details
%K tandem geminal dihalogenation
%X 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 Δ16-alkene reduction with Raney Ni provided cortistatin A. With this scalable and practical route, copious quantities of cortistatinone, Δ16-cortistatin A (the equipotent direct precursor to cortistatin A), and its related analogues were prepared for further biological studies.
%I ACS Publications