Development and evaluation of Pirkle-type chiral stationary phase for flash chromatography

Liquid chromatography is the most applied methodology for enantioseparation in preparative and semi-preparative scale; however, flash chromatography is seldom the first choice. This work proposes a new sustainable method to achieve pure enantiomers in mg scale. Herein, the functionalization of silica for flash chromatography columns with a suitable chiral selector, for subsequent quantitative enantiosepara-tion of chiral compounds, is described. Accordingly, the Whelk-O (R) 1 chiral selector was bonded to flash silica and packed into a reused solid phase extraction cartridge. For the evaluation of the enantioselective performance of the flash column, the enantiomers of a chiral derivative of xanthone were quantitatively enantioseparated with an average recovery of 70% and an enantiomer ratio (e.r.) of 99% and 97% for each enantiomer. Evaluation with the anti-inflammatory drug naproxen was also performed, resulting in an av-erage recovery of 95% and 89% and 95% e.r. for each enantiomer. The flash column showed high stability and load ability, versatility, and good reproducibility.(c) 2022 Elsevier B.V. All rights reserved.

Automated summary

This study proposes a new sustainable method for the preparative separation of pure enantiomers at milligram scale using flash chromatography. The functionalization of silica for flash chromatography columns is described, and the results show high stability, load ability, and reproducibility of the method.