Conformational analogies of morphine agonists and antagonists as revealed by carbon-13 NMR spectroscopy

The extreme similarity (except in the vicinity of the nitrogen atom) of the ¹³C spectra of the agonist-antagonist pairs oxymorphone-naloxone and morphine-nalorphine and their respective hydrochlorides suggests that the N-methyl and N-allyl compounds have analogous conformations. This makes unlikely an interpretation of the agonist-antagonist dichotomy in terms of confonnational differences. Both morphine hydrochloride and nalorphine hydrochloride exist as mixtures of two diastereomers: ca 83% of the isomer with equatorial N-alkyl and 17% of the isomer with axial N-alkyl (ΔG°=O.95 kcalmol^?1).