The crystal and molecular structure of 14-β-N-pentylaminomorphinone, C₂₂H₂₈N₂O₃

Abstract

The crystal and molecular structure of 14-β-N-pentylaminomorphinone (14-β-N-PAM), C₂₂H₂₈N₂O₃, has been determined by analysis of single crystal X-ray diffraction data. The compound crystallized at room temperature in the orthorhombic system, space group P2₁2₁2₁ witha=12.4535(8),b=13.7855(8),c=11.710(1) Å,V _c =2010.3(2) ų,Z=4,D _x =1.22 gm/cm³,μ(Cu Kα)=6.58 cm⁻¹, andF(000)=792. The final refinement yieldedR=0.051,R _w =0.059 for 328 variables with 1133 unique observed reflections. The absolute configuration is established via the synthesis from thebaine by the noninvolvement of certain asymmetric centers. The molecule is found to have as its central structure a T shape similar to that found in morphine and codeine. The distinctive feature of the molecule is the 14-β-N-pentylamino lipophilic side chain. Molecular modeling studies on the alkylamino chain result in the identification of clusters of conformations based on energy and dihedral angle criteria. Selected conformations are compared to 19-propylthevinol (etorphine), another potent analgesic which contains a lipophilic hydroxyalkyl substituent at C19. The enhanced analgesic activity of 14-β-N-pentylaminomorphinone is postulated to arise from an overall morphine-like contact with the receptor augmented by the interaction of the aliphatic chain with a lipophilic receptor pocket.