title: Ultrafast chiral separations for high throughput enantiopurity analysis.
abstract: Recent developments in fast chromatographic enantioseparations now make high throughput analysis of enantiopurity on the order of a few seconds achievable. Nevertheless, routine chromatographic determinations of enantiopurity to support stereochemical investigations in pharmaceutical research and development, synthetic chemistry and bioanalysis are still typically performed on the 5-20 min timescale, with many practitioners believing that sub-minute enantioseparations are not representative of the molecules encountered in day to day research. In this study we develop ultrafast chromatographic enantioseparations for a variety of pharmaceutically-related drugs and intermediates, showing that sub-minute resolutions are now possible in the vast majority of cases by both supercritical fluid chromatography (SFC) and reversed phase liquid chromatography (RP-LC). Examples are provided illustrating how such methods can be routinely developed and used for ultrafast high throughput analysis to support enantioselective synthesis investigations.
authors.affiliation: Process Research & Development, MRL, Merck & Co., Inc., Rahway, NJ 07065, USA. erik.regalado@merck.com christopher_welch@merck.com and Department of Chemistry, University of Texas at Arlington, Arlington, TX 76019, USA.
authors.forename: Chandan L
authors.initials: CL
authors.lastname: Barhate
authors.affiliation: Process Research & Development, MRL, Merck & Co., Inc., Rahway, NJ 07065, USA. erik.regalado@merck.com christopher_welch@merck.com.
authors.forename: Leo A
authors.initials: LA
authors.lastname: Joyce
authors.affiliation: Process Research & Development, MRL, Merck & Co., Inc., Rahway, NJ 07065, USA. erik.regalado@merck.com christopher_welch@merck.com.
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Makarov
authors.affiliation: Process Research & Development, MRL, Merck & Co., Inc., Rahway, NJ 07065, USA. erik.regalado@merck.com christopher_welch@merck.com.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Zawatzky
authors.affiliation: Process Research & Development, MRL, Merck & Co., Inc., Rahway, NJ 07065, USA. erik.regalado@merck.com christopher_welch@merck.com.
authors.forename: Frank
authors.initials: F
authors.lastname: Bernardoni
authors.affiliation: Process Research & Development, MRL, Merck & Co., Inc., Rahway, NJ 07065, USA. erik.regalado@merck.com christopher_welch@merck.com.
authors.forename: Wes A
authors.initials: WA
authors.lastname: Schafer
authors.affiliation: Department of Chemistry, University of Texas at Arlington, Arlington, TX 76019, USA.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Armstrong
authors.affiliation: Process Research & Development, MRL, Merck & Co., Inc., Rahway, NJ 07065, USA. erik.regalado@merck.com christopher_welch@merck.com.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Welch
authors.affiliation: Process Research & Development, MRL, Merck & Co., Inc., Rahway, NJ 07065, USA. erik.regalado@merck.com christopher_welch@merck.com.
authors.forename: Erik L
authors.identifier: 0000-0002-7352-6391
authors.initials: EL
authors.lastname: Regalado