Stereochemical assignment of the enantiomers of omeprazole from X-ray analysis of a fenchyloxymethyl derivative of (+)-(R)-omeprazole

The absolute configurations of the enantiomers of the H+,K+-ATPase inhibitor omeprazole 1 have been determined by an X-ray crystallographic study of a derivative of (+)-(R)-1. The examined compound 6-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]-(R)-sulfinyl]-1-[[[(1R-endo)-1,3,3-trimethylbicyclo[2.2.1]hept-2-yl]oxy]methyl]-1H-benzimidazole 4 was synthesized from enantiomerically pure (1R-endo)-2-(chloromethoxy)-1,3,3-trimethylbicyclo[2.2.1]heptane 2 and enantiomerically pure (+)-(R)-1. Finally, enantiomerically, diastereomerically and regioisomerically pure 4 was converted back to (+)-(R)-1 in order to verify that no stereomutation had occurred on sulfur during the synthesis of 4. (C) 1997 Elsevier Science Ltd.