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利用开放获取的手性超临界流体色谱法实现发现化学中的手性分离。

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

作者信息

Michaels Philip, Neef James, Galyan Keith, Ginsburg-Moraff Carol, Zhou Xilin, Dunstan David, Poirier Jennifer, Reilly John

机构信息

Novartis Institutes for Biomedical Research, Cambridge, Massachusetts.

出版信息

Chirality. 2019 Aug;31(8):575-582. doi: 10.1002/chir.23081. Epub 2019 Jun 13.

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 UPC and Prep100-SFC instrumentation.

摘要

本文的研究详细介绍了一种新颖的即到即用型开放获取(OA)方法,该方法可利用超临界流体色谱法(SFC)在早期药物发现化学中实现手性分析方法开发和对映体的制备分离。我们已经通过使用固定化手性固定相(CSP)证明了这种OA方法的成功。在筛选了一系列不同的外消旋候选药物后,我们得出结论,一个简化的OA手性SFC平台能够成功纯化约60%的分析外消旋体。这种简化的OA工作流程使在手性方法开发方面专业知识有限的药物化学家能够使用沃特世UPC和Prep100-SFC仪器,为他们的项目成功且快速地纯化对映体。

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