Enabling chiral separations in discovery chemistry with open‐access chiral supercritical fluid chromatography

Abstract

Work from this paper details a novel walk‐up open‐access (OA) approach to enable chiral analytical method development and preparative separation of enantiomers in early discovery chemistry using supercritical fluid chromatography (SFC). We have demonstrated the success of this OA approach using immobilized chiral stationary phases (CSPs). After screening a diverse set of racemic drug candidates, we have concluded that a simplified OA chiral SFC platform can successfully purify approximately 60% of the analysed racemates. This streamlined OA workflow enables medicinal chemists with limited expertise in chiral method development to successfully and rapidly purify enantiomers for their projects using Waters UPC2 and Prep100‐SFC instrumentation.

GreenMedChem: the challenge in the next decade toward eco-friendly compounds and processes in drug design

“…162 As mentioned above, one of the essential aspects of this field is transforming renewable, biological materials into oxygenated raw materials to form alternative solvents. Cyrene is mainly synthesised from levoglucosenone (LGO) (138), an intermediate obtained from the degradation of cellulose (Fig. 33A).…”

“…137 To focus on a more specific field of application, we chose an impressive example dealing with chiral analytical method development and preparative separation of enantiomers. This topic was investigated by Michaels et al , 138 whose group worked on an open-access approach using immobilised chiral stationary phases such as CHIRALPAK® IG, a rapid and efficient method to separate chiral compounds. To collect the needed data, they set a core screening process using methanol as a co-solvent for 50 different compounds.…”

Sub/supercritical Fluid Chromatography for Chiral Compounds Analysis

“…Někteří autoři používají při vývoji těchto metod pouze CSF na bázi derivatizovaných polysacharidů, což je dáno možností výběru z velkého množství jejich derivátů, a tím zajištění enantioselektivity pro široké spektrum strukturně odlišných chirálních sloučenin 22,44,75 . V několika publikovaných postupech jsou zařazeny kromě CSF založených na derivatizovaných polysacharidech také CSF na bázi makrocyklických glykopeptidů a Pirklovy fáze 76,77 . Navržené postupy pro chirální screening v posledních 20 letech jsou shrnuty a kriticky zhodnoceny v nedávno publikovaném přehledu 70 .…”

Chiral Separations in Preparative Scale: A Medicinal Chemistry Point of View

“…Recently, a novel walk-up open-access (OA) approach to enable chiral analytical method development and preparative separation of enantiomers in early discovery chemistry using SFC was reported [84]. They proved that the key of the robust nature of the platform is the use of immobilized CSPs.…”