Synthesis and Characterization of New 7-Substituted 6,14-Ethenomorphinane Derivatives: N-{5-[(5 alpha,7 alpha)-4,5-Epoxy-3,6-dimethoxy-17-methyl-6,14-ethenomorphinan-7-yl]-1,3,4-oxadiazol-2-yl}arenamines


HELVETICA CHIMICA ACTA, vol.93, no.12, pp.2406-2418, 2010 (Journal Indexed in SCI) identifier identifier

  • Publication Type: Article / Article
  • Volume: 93 Issue: 12
  • Publication Date: 2010
  • Doi Number: 10.1002/hlca.201000083
  • Title of Journal : HELVETICA CHIMICA ACTA
  • Page Numbers: pp.2406-2418


In this study, (5 alpha,7 alpha)-4,5-epoxy-3,6-dimethoxy-17-methyl-6,14-ethenomorphinan-7-carboxylic acid hydrazide (5) was synthesized by the condensation of methyl (5 alpha,7 alpha)-4,5-epoxy-3,6-dimethoxy-17-methyl-6,14-ethenomorphinan-7-carboxylate (4) with NH2NH2 center dot H2O. The (5 alpha,7 alpha)-4,5-epoxy-3,6-dimethoxy-17-methyl-6,14-ethenomorphinan-7-carboxylic acid 2-[(arylamino)carbonyl]hydrazides 6a-6q were prepared by the reaction of 5 with corresponding substituted aryl isocyanates, and the N-{5-[(5 alpha,7 alpha)-4,5-epoxy-3,6-dimethoxy-17-methyl-6,14-ethenomorphinan-7-yl]-1,3,4-oxadiazol-2-yl}arenamines 7a-7q were obtained via the cyclization reaction of 6a-6q in the presence of POCl3. The synthesized compounds have a rigid morphine structure, including the 6,14-endo-etheno bridge and the 5-(arylamino)-1,3,4-oxadiazol-2-yl residue at C(7) adopting the (S)-configuration (7 alpha). The structures of the compounds were confirmed by high-resolution mass spectrometry (HR-MS) and various spectroscopic methods such as FT-IR, H-1-NMR, C-13-NMR, APT, and 2D-NMR (HETCOR, COSY, INADEQUATE).