Synthesis of nalbuphine and investigation of several mixtures of nalbuphine with other drugs for BALB/c mice anesthesia

In this research, the conversion of thebaine into oxycodone was achieved using oxidizing reagents, with a yield of 80%. Subsequently, oxycodone was converted into oxymorphone in the presence of an acidic environment, resulting in a yield of 55%. The synthesized oxymorphone was then de-methylated using ethyl chloroformate to obtain the intermediate noroxymorphone. The latter was further transformed into nalbuphone using cyclobutyl methyl bromide reagent, with a yield of 82%. Finally, nalbuphone was converted into nalbuphine using a reducing reagent, with a yield of 75%. The identification of all intermediates was ensured through the use of NMR, FT-IR, Mass, and HPLC spectroscopy. The chemical transformations were primarily associated with the formation of noroxymorphone, which served as a crucial intermediate in the synthesis of nalbuphin. Additionally, the effects of three drugs, namely azaperone, medetomidine, and nalbuphine, were investigated on BALB/c mice. The results showed that the best formulation for short-term anesthesia of mice was a combination of the three drugs, each at a concentration of 1 mg/kg of body weight.