Stereospecific synthesis of the 6beta-hydroxy metabolites of naltrexone and naloxone.
The narcotic antagonists naltrexone (1a) and naloxone (2a) were stereospecifically reduced to the corresponding 6beta-hydroxy epimers 1b and 2b, respectively, with formamidinesulfinic acid in an aqueous alkaline medium. The reaction products were obtained with no detectable quantity of the 6alpha epimers 1c and 2c. The products 1b and 2b were formed in yields of 88.5 and 40%, respectively, and characterized by spectral methods. Compared to 1a and 2a, the stereospecific reduction products 1b and 2b and their 6alpha epimers 1c and 2c are all significantly less potent as narcotic antagonists in mice. Only 1c and 2c also possess antinociceptive activity.
D000818:Animals; D003521:Cyclopropanes / Q000138:chemical synthesis / Q000494:pharmacology; D051379:Mice; D009019:Morphinans / Q000138:chemical synthesis* / Q000494:pharmacology; D009270:Naloxone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D010146:Pain; D011809:Quinones / Q000037:antagonists & inhibitors; D011930:Reaction Time / Q000187:drug effects; D013237:Stereoisomerism
D003521:Cyclopropanes; D009019:Morphinans; D009292:Narcotic Antagonists; D011809:Quinones; D009270:Naloxone