Chiral Analysis of Pharmaceuticals Using NMR Spectroscopy: A Review

Abstract

Chirality recognition of pharmaceutical products plays a significant part in asymmetric synthesis, stereoselective catalysis, supramolecular chemistry, and the development of new drug substances. NMR spectroscopy is a potential technique utilized not only for the determination of chemical structure but also for chirality analysis. Three main approaches are developed for the assessment of the chirality of organic compounds through NMR spectroscopy that depends on the use of chiral discriminating agents such as chiral solvating agents, and chiral derivatizing agents. This article highlights the recent advances in chiral recognition of pharmaceutically important compounds using NMR spectroscopic methods.

Enantiospecific Analysis of Carboxylic Acids Using Cinchona Alkaloid Dimers as Chiral Solvating Agents

“…The induction of enantiodifferentiation is due to the in situ formation of diastereoisomeric complexes between the CSA and the two enantiomers of the racemate into the NMR tube via noncovalent interactions, the chemical shift difference (ΔΔδ) for the diastereomeric pairs would start appearing. During the past half a century, several comprehensive reviews and application oriented articles on chiral distinction using NMR spectroscopy have been published. − …”

19F NMR enantiodiscrimination and diastereomeric purity determination of amino acids, dipeptides, and amines

“…Chiral amino-group compounds are not only important biomolecules but also chemical and pharmaceutical intermediates for the synthesis of bioactive compounds. Currently, various methods have been widely used for the elucidation of absolute configuration and enantiomeric excess (ee), including NMR, [1][2][3][4][5][6][7][8][9][10][11][12] circular dichroism, [13][14][15][16][17] fluorescence, 18 SERS, 19 chromatography, 20,21 ion mobility mass spectrometry, 22 and electrochemistry. 23,24 However, optical spectroscopic techniques require pure enantiomers that are obtained by isolating each enantiomeric pair or by extracting each enantiomer from its original matrix prior to analysis.…”