A Novel Mechanism of Preferential Enrichment Phenomenon Observed for the Cocrystal of (RS)-2-{4-[(4-Chlorophenoxy)methyl]phenoxy}propionic Acid and Isonicotinamide

被引：5

作者：

Takahashi, Hiroki ^{[1
]}

Numao, Yuki ^{[2
]}

Motokawa, Junko ^{[1
]}

Clevers, Simon ^{[3
]}

Coquerel, Gerard ^{[3
]}

Tsue, Hirohito ^{[1
]}

Tamura, Rui ^{[1
]}

机构：

[1] Kyoto Univ, Grad Sch Human & Environm Studies, Sakyo Ku, Yoshida Nihonmatsu Cho, Kyoto 6068501, Japan

[2] Kyoto Univ, Fac Integrated Human Studies, Sakyo Ku, Yoshida Nihonmatsu Cho, Kyoto 6068501, Japan

[3] Univ Rouen, Normandie Univ, Crystal Genesis Unit, SMS,EA 3233, F-76821 Mont St Aignan, France

来源：

CHEMISTRY-A EUROPEAN JOURNAL | 2019年 / 25卷 / 71期

关键词：

cocrystal; crystal growth; preferential enrichment; second harmonic generation; spontaneous resolution; HYDROGEN-BOND PATTERNS; CRYSTAL-STRUCTURE; ENANTIOMERIC RESOLUTION; POLYMORPHIC TRANSITION; CO-CRYSTAL; CRYSTALLIZATION; RECRYSTALLIZATION; NICOTINAMIDE; MICROSCOPY; IBUPROFEN;

D O I：

10.1002/chem.201904130

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A new entry of chiral anti-hyperlipoproteinemia drug is reported, showing an excellent preferential enrichment (PE) phenomenon which is not caused by a polymorphic transition during crystallization, but is proposed to occur by a novel mechanism involving partially irregular stacking of R and S homochiral two-dimensional (2D) sheets with a large dipole moment, followed by selective redissolution of one homochiral 2D sheet into the mother liquor during crystallization. The cocrystal composed of (RS)-2-{4-[(4-chlorophenoxy)methyl]phenoxy}propionic acid (CPPPA) and achiral isonicotinamide exhibited a substantial enrichment in the mother liquor up to 93 % ee by simply repeating recrystallization under nonequilibrium conditions using high supersaturation. Furthermore, the deposited crystals with low ee values obtained at the end of PE experiment were second harmonic generation (SHG)-positive, indicating the formation of homochiral domains in the deposited crystals, which reflects the proposed mechanism of PE.

引用

页码：16405 / 16413

页数：9