Title :

Small scale separation of isoxazole structurally related analogues by chiral supercritical fluid chromatography

Author(s) :

Zehani, Yasmine [Auteur]
Lemaire, Lucas [Auteur]
MILLET, Régis [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Lille Inflammation Research International Center - U 995 [LIRIC]
Lipka, Emmanuelle [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Lille Inflammation Research International Center - U 995 [LIRIC]

Journal title :

Journal of chromatography. A

Abbreviated title :

J. Chromatogr. A

Volume number :

1505

Pages :

106-113

Publication date :

2017-07-07

ISSN :

0021-9673

English keyword(s) :

Supercritical fluid chromatography
Amylose tris (3,5-dimethylphenylcarbamate)
Productivity
Environmental factor
Evaporative light scattering detector

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Chromatographic preparative enantioseparation is now the preferred method to obtain milligram amounts of pure enantiomers in the first step of the development of a therapeutic molecule. Supercritical fluid chromatography ...
Show more >Chromatographic preparative enantioseparation is now the preferred method to obtain milligram amounts of pure enantiomers in the first step of the development of a therapeutic molecule. Supercritical fluid chromatography has many advantages over liquid chromatography and was therefore chosen for the small scale enantioseparation of four original 3-carboxamido-5-aryl isoxazole molecules, ligands of the CB2 cannabinoid receptors. The preparation of about 10mg of each of the eight enantiomers was achieved successfully on a Chiralpak AD-H (tris-3,5-dimethylphenylcarbamate of amylose) polysaccharide based stationary phase with various percentages of ethanol as a co-solvent, through mixed-stream injections and touching-band approach. For the all compounds, no peak distortion is observed during the volume overloading, in spite of the injection mode. Production rate (mgmin), productivity (kilogram of racemate separated per kilogram of CSP per day (kkd)) and solvent usage were found higher and environmental factors (E Factor) were found lower for compounds 1 and 3. The yields of each purified enantiomer were comprised between 60 and 94%. In order to improve the limit of detection calculated with the diode array detector, the hyphenation with an evaporating light scattering detector was explored and a factor of ten was won. Lastely, the enantiomeric excess and achiral purity of each of the eight individual enantiomer generated was determined and found higher than 98%.Show less >

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CHU Lille
Inserm
Université de Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Research team(s) :

Therapeutic innovation targetting inflammation

Submission date :

2019-05-17T13:14:41Z