%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