Purification of high-throughput organic synthesis libraries by counter-current chromatography.
Experiments were performed to evaluate whether counter-current chromatography (CCC) could function as an alternative purification method to reversed-phase high-performance liquid chromatography (RP-HPLC) and normal-phase supercritical fluid chromatography (SFC). RP-HPLC and SFC are the routine methods currently used in our high-throughput purification (HTP) facility for the purification of high-throughput organic synthesis (HTOS) libraries and medicinal chemistry reaction mixtures. Pre-equilibration of the solvent mixture layers was not mandatory for effective chromatography when hexanes-ethyl acetate-methanol-water (HEMW) solvent mixtures were used. Key to the use of CCC for high-throughput applications is the ability to effectively select a solvent system appropriate to each library member. Pilot-scale CCC elution time was used to estimate a starting solvent ratio and RP-HPLC retention time was then used to adjust solvent ratios within a particular library. It was also found that dimethyl sulfoxide (DMSO) and DMSO-methanol were suitable as sample injection solvents when using the HEMW solvent systems.
Wagenaar
Frank L
FL
Abbott Laboratories, Abbott Park, IL 60064, USA. frank.wagenaar@abbott.com
Hochlowski
Jill E
JE
Pan
Jeffrey Y
JY
Tu
Noah P
NP
Searle
Philip A
PA
D000215:Acylation; D002851:Chromatography, High Pressure Liquid; D003377:Countercurrent Distribution / Q000379:methods*; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D004867:Equipment Design; D007052:Ibuprofen / Q000302:isolation & purification; D007660:Ketoprofen / Q000302:isolation & purification; D000432:Methanol / Q000737:chemistry; D009930:Organic Chemicals / Q000737:chemistry*; D054852:Small Molecule Libraries; D012995:Solubility; D012997:Solvents / Q000737:chemistry
D009930:Organic Chemicals; D054852:Small Molecule Libraries; D012997:Solvents; D007660:Ketoprofen; D007052:Ibuprofen; D000432:Methanol; D004121:Dimethyl Sulfoxide