Strategy for large-scale isolation of enantiomers in drug discovery. Issue 1 (January 2017)

• Record Type: Journal Article
• Authors: Leek, Hanna; Thunberg, Linda; Jonson, Anna C.; Öhlén, Kristina; Klarqvist, Magnus
• Is Part Of: Drug discovery today. Volume 22:Issue 1(2017)
• Page Start: 133
• Page End: 139
• Publication Date: 2017-01
• Subjects: Drugs -- Design -- Periodicals; Drugs -- Research -- Periodicals; 615.1
• DOI: 10.1016/j.drudis.2016.09.018
• Languages: English
• ISSNs: 1359-6446

Abstract

Highlights: SFC is a superior separation technique for isolation of enantiomers. A crucial factor for success in SFC is solubility of the compound in the mobile phase. Extraction injection is a promising injection technique for compounds with low solubility. A defined strategy, including a broad separation tool box, was key for successful delivery. Abstract : A strategy for large-scale chiral resolution is illustrated by the isolation of pure enantiomer from a 5 kg batch. Results from supercritical fluid chromatography will be presented and compared with normal phase liquid chromatography. Solubility of the compound in the supercritical mobile phase was shown to be the limiting factor. To circumvent this, extraction injection was used but shown not to be efficient for this compound. Finally, a method for chiral resolution by crystallization was developed and applied to give diastereomeric salt with an enantiomeric excess of 99% at a 91% yield. Direct access to a diverse separation tool box will be shown to be essential for solving separation problems in the most cost and time efficient way.