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Paper | Special issue | Vol 69, No. 1, 2006, pp.271-282
Published online, 22nd August, 2006
DOI: 10.3987/COM-06-S(O)27
■ A New Useful Conversion Method of Naltrexone to 14-Deoxynaltrexone

Yumiko Osa, Yoshihiro Ida, Yumiko Yano, Kimio Furuhata, and Hiroshi Nagase*

*School of Pharmaceutical Sciences, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo 108-8641, Japan

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 PtO2 under hydrogen to give saturated compound (27), which was then acid-hydrolyzed to afford the desired 14-deoxynaltrexone (23) (3-O-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 selective ligands for the opioid receptor subtypes.