The ^1H NMR and stereochemistry of four ohmefentanyl enantiomers, (-)-cis-(3R,4S,2'R)-OMF (1), (+)-cis-(3-R,4S,2'S)-OMF (2), (+)-trans-(3S,4S,2'R)-OMF (3), and (+)-trans-(3S,4S,2'S)-OMF (4), were analyzed with the combination of several one- and two-dimensional NMR techniques. The vicinal coupling constants between the piperidine ring protons were consistent with the piperidine ring assuming a chair conformation with an equatorial 4-N-phenylpropanamide group. In cis-isomers, the 3-He and 5-He signals were 1.1 downfield and 0.5 upfield from the corresponding signals in trans-isomers due to the deshielding and shielding effects of C=O groups and N-phenyl rings, respectively. This suggested that the steric position and orientation of 4-N-phenylpropanamide groups are relatively fixed in cis-isomers, owing to the intramolecular hindrance of axial 3-methyl. While in trans-isomers, the 4-N-phenylpropanamide groups maybe possess various orientations, as investigated by the variable temperature NMR experiments.

Key words: PROTON MAGNETIC RESONANCE SPECTROMETRY, ISOMER, STEREOCHEMISTRY, ANALGESICS, OHMEFENTANYL