Enantioselective chromatography in drug discovery.
Molecular chirality is a fundamental consideration in drug discovery, one necessary to understand and describe biological targets as well as to design effective pharmaceutical agents. Enantioselective chromatography has played an increasing role not only as an analytical tool for chiral analyses, but also as a preparative technique to obtain pure enantiomers from racemates quickly from a wide diversity of chemical structures. Different enantioselective chromatography techniques are reviewed here, with particular emphasis on the most widespread high performance liquid chromatography (HPLC) and the rapidly emerging supercritical fluid chromatography (SFC) techniques. This review focuses on the dramatic advances in the chiral stationary phases (CSPs) that have made HPLC and SFC indispensable techniques for drug discovery today. In addition, screening strategies for rapid method development and considerations for laboratory-scale preparative separation are discussed and recent achievements are highlighted.
Zhang
Yingru
Y
Discovery Analytical Sciences, Pharmaceutical Research Institute, Bristol-Myers Squibb Company, P. O. Box 4000, Princeton, NJ 08648-4000, USA. yingru.zhang@bms.com
Wu
Dauh-Rurng
DR
Wang-Iverson
David B
DB
Tymiak
Adrienne A
AA
D000688:Amylose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods / Q000639:trends; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000639:trends; D025924:Chromatography, Supercritical Fluid / Q000379:methods / Q000639:trends*; D004345:Drug Industry / Q000379:methods / Q000639:trends*; D048448:Phenylcarbamates / Q000737:chemistry; D013237:Stereoisomerism
D048448:Phenylcarbamates; C080033:Chiralpak AD; D000688:Amylose