A NEW USEFUL CONVERSION METHOD OF NALTREXONE TO 14-DEOXYNALTREXONE

摘要

A novel synthetic method of 14-deoxynaltrexone(2),a mu-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-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 selectives ligands for the opioid receptor subtypes.