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

Abstract

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.