A comparison of solution, solid state and theoretical conformations of morphine

Abstract

Summary Using very high frequency 1 H nuclear magnetic resonance, nitrogen inversion in the N-substituted piperidine ring of a fused polycyclic molecule is demonstrated for the first time. The molecule discussed is the potent opiate agonist morphine where the piperidine ring is known to be of vital importance in receptor mediated pharmacological action. Previously, it has been accepted that the conformation of the piperidine ring was solely N-R, equatorial, on the basis of solid state and theoretical conformation studies. The present work demonstrates a relatively slow rate of interchange between the axial and equatorial forms and therefore requires a reappraisal of the previous literature as applied to the receptor active conformation of morphine.