Radical Multicomponent Carboamination of [1.1.1]Propellane.
Three-dimensional, small-ring scaffolds are very important in modern drug discovery to expand the available drug-like chemical space and to optimize drug candidates. Among them, bicyclo[1.1.1]pentane (BCP) is regarded as a high-value bioisostere for a phenyl ring or tert-butyl group; it provides an...
| Publicado en: | Journal of the American Chemical Society Vol. 139; no. 49; pp. 17791 - 17795 |
|---|---|
| Autores principales: | , , |
| Formato: | Artículo |
| Publicado: |
American Chemical Society
12/13/2017
|
| Materias: | |
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=hlh&AN=126761905&site=ehost-live header: @attributes: shortDbName: hlh uiTerm: 126761905 longDbName: Humanities International Complete uiTag: AN controlInfo: bkinfo: jinfo: jid: 00027863 ACS jtl: Journal of the American Chemical Society issn: 00027863 maglogo: N pubinfo: dt: 12/13/2017 vid: 139 iid: 49 pid: 997 pub: American Chemical Society artinfo: ui: 126761905 10.1021/jacs.7b11865 ppf: 17791 ppct: 4 formats: tig: atl: Radical Multicomponent Carboamination of [1.1.1]Propellane. aug: au: Junichiro Kanazawa Katsuya Maeda Masanobu Uchiyama affil: Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan Elements Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan su: Propellanes Amination Pentane Amines Density functional theory Drug development sug: subj: Propellanes Amination Pentane Amines Density functional theory Drug development ab: Three-dimensional, small-ring scaffolds are very important in modern drug discovery to expand the available drug-like chemical space and to optimize drug candidates. Among them, bicyclo[1.1.1]pentane (BCP) is regarded as a high-value bioisostere for a phenyl ring or tert-butyl group; it provides an option to generate drug-like molecules with good passive permeability, high aqueous solubility, and improved metabolic stability, though the lack of methodology to functionalize BCP remains a significant challenge. Here we present an efficient method, developed with the aid of density functional theory calculations, for the synthesis of multifunctionalized BCP derivatives by means of a radical multicomponent carboamination of [1.1.1]propellane. This reaction features mild conditions, one-pot operation, and gram-scale synthetic capability, and opens up a unique and highly efficient route for the synthesis of multifunctionalized BCP derivatives, including synthetically useful 3-substituted BCP-amines. pubtype: Academic Journal doctype: Article src: R language: English refInfo: copyright: @attributes: flag: Y dt: @attributes: year: 2017 holdings: @attributes: islocal: N |
|---|