H-1-NMR AND STEREOCHEMISTRY OF OHMEFENTANYL ENANTIOMERS

The H-1 NMR and stereochemistry of four ohmefentanyl enantiomers, (-)- cis-(3R,4S, 2'R)-OMF (1), (+)-cis-(3R,4S,2'S)-OMF (2), (+)-trans-(3S,4 S,2'R)-OMF (3) and (+)-trans(3S,4S,2/S)-OMF (4), were analyzed with th e combination of several one- and two-dimensional NMR techniques. The vicinal coupling constants between the piperidine ring protons were co nsistent with the piperidine ring assuming a chair conformation with a n equatorial 4-N-phenylpropanamide group. In cis-isomers, the 3-H-e an d 5-H-e signals were 1.1 downfield and 0.5 upfield from the correspond ing signals in transisomers due to the deshielding and shielding effec ts of C=O groups and N-phenyl rings, respectively. This suggested that the steric position and orientation of 4-Nphenylpropanamide groups ar e relatively fixed in cis-isomers, owing to the intramolecular hindran ce of axial 3-methyl. While in trans-isomers, the 4-N-phenylpropanamid e groups maybe possess various orientations, as investigated by the va riable temperature NMR experiments.