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.