Prediction of the Absolute Configuration of Chiral Drugs by NMR Spectroscopy

An NMR-based method was developed for the prediction of the absolute configuration of chiral carboxylic acids exemplified by over-the-counter drug naproxen. In this method, a pair of diastereomers were generated by purification and chiral derivatization of naproxen, whose absolute configuration was predicted by the difference in chemical shifts due to the magnetic shielding effects of phenyl functional group. The paper further illustrated the role of the related methods of Mosher ester analysis in the determination of absolute stereochemistry of carboxylic acids in addition to the derivatization and analysis of chiral secondary alcohols and amines.