Synthesis and Characterization of New Thebaine Derivatives as Potential Opioid Agonists and Antagonists: 2-[N-(1H-Tetrazol-5-yl)-6,14-endo-etheno-6,7,8,14-tetrahydrothebaine-7 alpha-yl]-5-phenyl-1,3,4-oxadiazoles

In this study, we report the synthesis a series of novel 2-[N-(1H-tetrazol-5-yl)-6,14-endo-etheno-6,7,8,14-tetrahydrothebaine-7-yl]-5-phenyl-1,3,4-oxadiazole derivatives (7ae) which have potential opioid antagonist and agonist. The substitution reaction of 6,14-endo-ethenotetrahydrothebaine-7-carbohydrazide with corresponding benzoyl chlorides gave diacylhydrazine compounds 4ae in good yields. The treatment of compounds 4ae with POCl3 caused the conversion of side-chain of compounds 5ae into 1,3,4-oxadiazole ring at C(7) position; thus, compounds 5ae were obtained. Subsequently, cyanamides (6ae) were prepared from compounds 5ae and then compounds 7ae were synthesized by the azidation of 6ae with NaN3. The structures of the compounds were established on the basis of their IR, 1H NMR, 13C APT, 2D-NMR (COSY, NOESY, HMQC, HMBC) and high-resolution mass spectral data.