A Novel Mechanism of Preferential Enrichment Phenomenon Observed for the Cocrystal of (RS)-2-{4-[(4-Chlorophenoxy)methyl]phenoxy}propionic Acid and Isonicotinamide.
Chemistry
; 25(71): 16405-16413, 2019 Dec 18.
Article
in En
| MEDLINE
| ID: mdl-31566820
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Chemistry
Journal subject:
QUIMICA
Year:
2019
Document type:
Article
Affiliation country:
Japón