Laboratoire de Chimie Thérapeutique, Faculté de Pharmacie , BioCIS, Univ. Paris-Sud, CNRS, University Paris-Saclay , Châtenay-Malabry , F-92296 , France.
Inserm UMR_S 999, Hôpital Marie Lannelongue , Le Plessis-Robinson , F-92350 , France.
J Org Chem. 2018 Apr 6;83(7):4264-4269. doi: 10.1021/acs.joc.8b00305. Epub 2018 Mar 12.
A convergent total synthesis of MK-801 has been achieved. Key synthetic transformations include a multicomponent Barbier-type reaction to construct the α-branched amine, a selective Heck α-coupling tactic to generate the exocyclic alkene skeleton, and a late-stage intramolecular hydroamination reaction between the exocyclic alkene and the secondary protected amine. The efficacy of this method was demonstrated by the synthesis of two news analogues substituted on the aromatic rings.
已实现了 MK-801 的收敛性全合成。关键的合成转化包括多组分 Barbier 型反应构建α-支链胺、选择性 Heck α-偶联策略生成外环烯烃骨架，以及外环烯烃和仲保护胺之间的晚期分子内氢胺化反应。该方法的功效通过两个在芳环上取代的新类似物的合成得到了证明。
