Oxilorphan and butorphanol. Potent narcotic antagonists and nonaddicting analgesics in the 3,14 dihydroxymorphinan series. Part V

Article abstract of DOI:10.1139/v75-439

A series of 3,14 dihydroxymorphinans 8 was synthesized via a method of (a) acylation of 3 methoxy Δ⁸⁴ morphinan 4a (b) stereospecific epoxidation of the resultant amides to β epoxides 5 (c) simultaneous reduction of amide and epoxide functions and (d) demethylation of the resultant 3 methoxy 14 hydroxymorphinans 7. Alternatively deblocking of the amine function in 5b by hydrolysis followed by reduction of the resultant amino epoxide 5e afforded 14 hydroxy 3 methoxymorphinan 7e, which is readily alkylated and demethylated to give various 8. On a basis of interesting pharmacological profiles compounds l 8c (oxilorphan) and l 8d (butorphanol) were selected for clinical studies.