Kuksenok Vera Yu, Shtrykova Victoria V, Filimonov Victor D, Druganov Alexandr G, Bondarev Alexandr A, Stankevich Ksenia S
The Kizhner Research Center, National Research Tomsk Polytechnic University, Tomsk, Russia.
N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia.
Chirality. 2018 Oct;30(10):1135-1143. doi: 10.1002/chir.23005. Epub 2018 Aug 3.
For the first time, a method for enantiomer resolution of the anticonvulsant Galodif (1-((3-chlorophenyl)(phenyl)methyl) urea) by chiral HPLC was developed, whereas the enantiomeric composition of 1-((3-chlorophenyl)(phenyl)methyl) amine-precursor in Galodif synthesis-cannot be resolved by this method. However, starting 1-((3-chlorophenyl)(phenyl)methyl) amine quantitatively forms diastereomeric N-((3-chlorophenyl)(phenyl)methyl)-1-camphorsulfonamides in reaction with chiral (1R)-(+)- or (1S)-(-)-camphor-10-sulfonyl chlorides. The diastereomeric ratio of obtained camphorsulfonamides can be easily determined by NMR H and C spectroscopy. The DFT calculations of specific rotation of Galodif enantiomers showed good agreement with experimental data. The absolute configuration of enantiomers was proposed for the first time.
首次开发了一种通过手性高效液相色谱法拆分抗惊厥药加洛迪夫（1-((3-氯苯基)(苯基)甲基)脲）对映体的方法，而加洛迪夫合成中1-((3-氯苯基)(苯基)甲基)胺前体的对映体组成不能用该方法拆分。然而，起始的1-((3-氯苯基)(苯基)甲基)胺与手性(1R)-(+)-或(1S)-(-)-樟脑-10-磺酰氯反应时定量形成非对映体N-((3-氯苯基)(苯基)甲基)-1-樟脑磺酰胺。所得樟脑磺酰胺的非对映体比例可通过核磁共振氢谱和碳谱轻松测定。加洛迪夫对映体比旋度的密度泛函理论计算结果与实验数据吻合良好。首次提出了对映体的绝对构型。
