Trapped in misbelief for almost 40 years: selective synthesis of the four stereoisomers of mefloquine.
Trapped in misbelief for almost 40 years: selective synthesis of the four stereoisomers of mefloquine.
复制标题
DOI：
10.1002/chem.201303403
复制
发表时间：
2013-12
期刊：
影响因子：
--
通讯作者：
Nina Schützenmeister;Michael Müller;U. Reinscheid;C. Griesinger;A. Leonov
中科院分区：
文献类型：
--
作者：
Nina Schützenmeister;Michael Müller;U. Reinscheid;C. Griesinger;A. Leonov
在这里，我们报告的所有四个立体异构体甲氟喹的合成。甲氟喹（Lariam）是一种重要的抗疟疾药物，其作为外消旋体形式应用。然而，（-）-异构体诱导精神病，而（+）-对映体没有这种不希望的副作用。有六个合成，其中五个导致错误的对映异构体，而这些合成的作者没有注意到他们合成了错误的化合物。与此同时，物理化学研究已经正确地指定了绝对构型，并且考虑到这些结果的最后一个对映选择性合成提供了正确的绝对构型。由于各种合成方法在以前的合成中未能提供正确的立体异构体，我们在这里提出了一种合成方法，其中多米诺Sonogashira-6π-电环化作为关键步骤，合成确认了所有四种异构体的正确绝对构型。
Here we report the synthesis of all four stereoisomers of mefloquine. Mefloquine (Lariam) is an important anti-malaria drug that is applied as a racemate of the erythro form. However, the (-)-isomer induces psychosis, while the (+)-enantiomer does not have this undesired side effect. There are six syntheses of which five lead to the wrong enantiomer without the authors of these syntheses noting that they had synthesized the wrong compound. At the same time physical chemistry investigations had assigned the absolute configuration correctly and the last enantioselective synthesis that took these results into account delivered the correct absolute configuration. Since various synthetic approaches failed to provide the correct stereoisomers in previous syntheses, we submit here a synthetic approach with a domino Sonogashira-6π-electrocyclisation as key step that confirmed synthetically the correct absolute configuration of all four isomers.