A Convenient Oxidation Method of the Benzylic 10-Position in 4,5-Epoxy-morphinan

Abstract

A convenient oxidation method of the benzylic 10-position in 4,5-epoxymorphinan to obtain its 10-oxo derivatives is described. The reaction by using potassium permanganate proceeds in good yield and can be performed in large scale.Three types of opioid receptors (µ, δ, κ) are now well established by not only pharmacological studies but also molecular biological studies. 1-3 Especially, the κ-opioid receptor has been of interest because its activation produces analgesia with minimum physical dependence and respiratory depression. 4 Thus, a highly selective κ-opioid agonist may provide a useful analgesic free from abuse potential and the adverse effects of a µ-agonist like morphine. 4,5 Oxo derivatives at the benzylic position of 4,5-epoxymorphinan and benzomorphan were described to possess more κ-receptor selectivity than the corresponding parent compounds, respectively. 6-8 In our research program searching for opioid receptor-type selective compounds, we focused on the 10-oxo derivatives of 4,5-epoxymorphinan compounds. In the field of