Use of (S)-BINOL as NMR Chiral Solvating Agent for the Enantiodiscrimination of Omeprazole and its Analogs

The application of (S)-1,1'-binaphthy1-2,2'-diol as NMR chiral solvating agent (CSA) for omeprazole, and three of its analogs (lanso-, panto-, and rabe-prazole) was investigated. The formation of diastereomeric host-guest complexes in solution between the CSA and the racemic substrates produced sufficient NMR signal splitting for the determination of enantiomeric excesses by H-1- or F-19-NMR spectroscopy. Using of hydrophobic deuterated solvents was mandatory for obtaining good enantiodiscrimination, thus suggesting the importance of intermolecular hydrogen bonds in the stabilization of the complexes. The method was applied to the fast quantification of the enantiomeric purity of in-process samples of S-omeprazole. Chirality 22:472-478, 2010. (C) 2009 Wiley-Liss, Inc.