6-Demethoxythebaine and its conversion to analgesics of the 6,14-ethenomorphinan type.
The 6-demethoxy analogue of thebaine has been easily prepared from codeine via isocodeine and its sulfenate ester. This diene, 7, readily undergoes reaction with vinyl ketones to afford Diels-Alder adducts of the 6,14-ethenomorphinan type. Further reactions afford the epimeric 19(R)- and 19(S)-butyl-6-demethoxy-7 alpha-orvinols (16). Pharmacological testing shows the R diastereomer to be highly analgesic and the s diastereomer to be a much less potent agonist, with similar potencies and relationships as found in the corresponding oripavine series. Thus, any hydrogen bonding between the 6-methoxyl group and the tertiary alcohol can be eliminated as contributory to either the activity of, or difference between the epimeric orvinols.
D000700:Analgesics / Q000138:chemical synthesis*; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004305:Dose-Response Relationship, Drug; D009019:Morphinans / Q000138:chemical synthesis*; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D013797:Thebaine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D013997:Time Factors
D000700:Analgesics; D009019:Morphinans; D013797:Thebaine; C005283:oripavine