Automated solvent system screening for the preparative countercurrent chromatography of pharmaceutical discovery compounds. Issue 23 (2nd December 2015)

• Record Type: Journal Article
• Authors: Bradow, James; Riley, Frank; Philippe, Laurence; Yan, Qi; Schuff, Brandon; Harris, Guy H.
• Is Part Of: Journal of separation science. Volume 38:Issue 23(2015:Dec.)
• Page Start: 3983
• Page End: 3991
• Publication Date: 2015-12-02
• Subjects: Automation -- Countercurrent chromatography -- Elution‐extrusion -- Mass‐directed separation -- Preparative chromatography; Separation (Technology) -- Periodicals; Chromatographic analysis -- Periodicals; 543.089
• DOI: 10.1002/jssc.201500574
• Languages: English
• ISSNs: 1615-9306

Abstract

Abstract : A fully automated countercurrent chromatography system has been constructed to rapidly screen the commonly used heptane/ethyl acetate/methanol/water solvent system series and translate the results to preparative scale separations. The system utilizes "on‐demand" preparation of the heptane/ethyl acetate/methanol/water solvent system upper and lower phases. Elution‐extrusion countercurrent chromatography was combined with non‐dynamic equilibrium injection reducing the screening time for each heptane/ethyl acetate/methanol/water system to 17 min. The result enabled solvent system development to be reduced to under 2 h. The countercurrent chromatography system was interfaced with a mass spectrometer to allow selective detection of target components in crude medicinal chemistry reaction mixtures. Mass‐directed preparative countercurrent chromatography purification was demonstrated for the first time using a synthetic tetrazole epoxide derived from a routine medicinal chemistry support workflow.