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1 H and 13 C NMR spectra of the opioid analgesics metazocine, pentazocine and cyclazocine
Author(s) -
Grassi Antonio,
Pappalardo Giuseppe C.,
Perly Bruno
Publication year - 1988
Publication title -
magnetic resonance in chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.483
H-Index - 72
eISSN - 1097-458X
pISSN - 0749-1581
DOI - 10.1002/mrc.1260260811
Subject(s) - chemistry , homonuclear molecule , heteronuclear molecule , pentazocine , nmr spectra database , chemical shift , proton , spectral line , proton nmr , stereochemistry , carbon 13 nmr , nuclear magnetic resonance spectroscopy , nuclear magnetic resonance , crystallography , molecule , organic chemistry , medicine , physics , quantum mechanics , astronomy , pharmacology , morphine
The high‐frequency 1 and 13 C NMR spectra (at 500 and 75.47 MHz, respectively) of metazocine (MTZ) fumarate, pentazocine (PTZ) and cyclazocine (CLZ) hydrochlorides in 2 H 2 O solution were recorded and analysed with the aid of both homonuclear 1 H 1 H and heteronuclear 13 C 1 H chemical shift correlation experiments. At neutral pH all compounds were found to be configurationally heterogeneous, with the N ‐equatorial isomer more populated than the N ‐axial isomer (ratio ca 80:20). The low‐intensity peaks of the superimposed spectral pattern of the less populated isomer were also assigned on correlative grounds in both the 1 H and 13 C NMR spectra of MTZ, PTZ and CLZ. The occurrence of distinct spectra for the two configurational isomers was diagnostic of a ‘slow’ exchange process on the NMR time‐scale at the field frequencies employed for the experiments, thus suggesting a high‐energy barrier to interconversion. The experimental proton–proton coupling constants measured for the N ‐equatorial form of MTZ, PTZ and CLZ were consistent with a chair conformation of the piperdinic ring in all compounds. The distinct relative agonist–antagonist potencies of the drugs investigated could therefore not be correlated with the above‐described configurational and conformational features.