A New Useful Conversion Method of Naltrexone to 14-Deoxynaltrexone

Abstract

A novel synthetic method of 14-deoxynaltrexone (2), a μ-opioid receptor antagonist possessing a new message-structural part of opioid ligands, was established. Naltrexone methyl ether (5) was first converted to its acetal (24), followed by dehydration with thionyl chloride in pyridine to afford 8,14-dehydroderivative (26) of 24. The resulting unsaturated compound (26) was reduced with PtO 2 under hydrogen to give saturated compound (27), which was then acid-hydrolyzed to afford the desired 14-deoxynaltrexone (23) (3-0-methyl of 2) without degradation of the naltrexone skeleton. The total yield from naltrexone (1) to 23 was 86%. Finally, 23 was demethylated to give 14-deoxynaltrexone (2) in 85% yield. This method provides a useful reaction route to give various important intermediates as a message part to synthesize selectives ligands for the opioid receptor subtypes.