On-line chiral analysis using the kinetic method

Abstract

Chiral analysis of constituents in solution-phase reaction mixtures can be performed by tandem mass spectrometry using the kinetic method to determine the enantiomeric excess (ee). Simply diluting an aliquot of a reaction mixture, adjusting the pH, and adding reagents necessary to form a chiral cluster ion allows chiral analysis. The product of a stereospecific N-selective alkylation reaction, 2-(3-(2-methoxyethoxy)-5-oxo-1,6-naphthyridin-6(5H)-yl)propanoic acid, was monitored for ee during the course of reaction, and it showed the expected inversion without ee erosion. Base-catalyzed racemization of the reaction product showed the expected decrease in ee as the reaction proceeded. The base-catalyzed racemization of ibuprofen was monitored on-line, providing near real-time data on ee.

Chiral differentiation of amino acids through binuclear copper bound tetramers by ion mobility mass spectrometry

“…Traditionally, a chiral selector is used to form diastereomers with the analyte enantiomers, and chiral recognition by mass spectrometry is based on comparison of generation of diastereomers in single-stage MS or dissociation of diastereomers in tandem MS [2][3][4][5][6][7][8][9][10][11].…”

Process Analytical Technology for Online Monitoring of Organic Reactions by Mass Spectrometry and UV–Vis Spectroscopy

“…15 Mass spectrometry (MS) has recently become important as a PAT instrument to monitor batch quality online 16 and to elucidate reaction mechanisms 17 and synthetic pathways 18 and is easily multiplexed to allow monitoring of multiple reaction vessels at the same time. 19 Online chemical derivatization to facilitate the determination of enantiomeric excess 20 as well as more common derivatization experiments to promote ionization efficiency have been reported. 19 Catalytic reactions 21,22 and air and water sensitive reactions 23 have been successfully monitored by mass spectrometry demonstrating the breadth of reactions this PAT tool can be utilized for.…”

Chiral detection of entecavir stereoisomeric impurities through coordination with R‐besivance and ZnII using mass spectrometry

“…Many analytical approaches have fewer applications in drugs with multiple chiral centers. Current research has largely concentrated on single chiral center molecules, such as amino acids, due to the difficulty separating the wide variety of multichiral‐center stereoisomers. While many clinical medicines have multiple chiral centers, it is necessary to expand the scope of application of MS to complex chiral drugs and increase the recognition efficiency of the method.…”