Preparative enantiomeric separation of potent AMP-activated protein kinase activator by HPLC on amylose-based chiral stationary phase. Determination of enantiomeric purity and assignment of absolute configuration.
The development of high performance liquid chromatography method on amylose-based stationary phases (Chiralpak AD) has permitted to achieve the preparative enantioseparation of one benzimidazole derivative, potent-AMP-kinase (AMPK) activator with satisfactory yields. Analytical enantioseparation method was optimized and validated to determine the enantiomeric purity. Using the UV detection, repeatability, limits of detection (LD) and quantification (LQ) were determined. Single-crystal X-ray analysis was successful to determine the absolute configuration of the individual enantiomers. A relation between the retention order and the absolute configuration of the enantiomers was established.
Vaccher
Marie-Pierre
MP
Laboratoire de Chimie Analytique, EA 4034, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Lille 2, 3 rue du Pr. Laguesse, BP 83, 59006 Lille Cédex, France.
Charton
Julie
J
Guelzim
Abdelhalim
A
Caignard
Daniel-Henry
DH
Bonte
Jean-Paul
JP
Vaccher
Claude
C
D055372:AMP-Activated Protein Kinases; D000688:Amylose / Q000031:analogs & derivatives* / Q000737:chemistry; D002021:Buffers; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D015394:Molecular Structure; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors*; D048448:Phenylcarbamates / Q000737:chemistry*; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D015203:Reproducibility of Results; D012997:Solvents / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
D002021:Buffers; D009097:Multienzyme Complexes; D048448:Phenylcarbamates; D047428:Protein Kinase Inhibitors; D012997:Solvents; C080033:Chiralpak AD; D000688:Amylose; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases