6-Demethoxythebaine and its conversion to analgesics of the 6,14-ethenomorphinan type
- 1 July 1981
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 24 (7) , 773-777
- https://doi.org/10.1021/jm00139a002
Abstract
The 6-demethoxy analog of thebaine was easily prepared from codeine via isocodeine and its sulfenate ester. This diene 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. Pharmacological testing [in rats] 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. Any H 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.This publication has 5 references indexed in Scilit:
- Aporphines. 27. Mechanistic aspects of the rearrangement of thebaine and codeine analogs in methanesulfonic acid. Improved method for the synthesis of N-alkylated aporphinesThe Journal of Organic Chemistry, 1980
- Intramolecular hydrogen bonding and conformational studies of bridged thebaine and oripavine opiate narcotic agonists and antagonistsJournal of Medicinal Chemistry, 1979
- 2,6-Methano-3-benzazocine-11-propanols. Lack of antagonism between optical antipodes and observation of potent narcotic antagonism by two N-methyl derivativesJournal of Medicinal Chemistry, 1978
- Analgesics. 1. Synthesis and analgesic properties of N-sec-alkyl and N-tert-alkylnormorphinesJournal of Medicinal Chemistry, 1978
- Aporphines. 23. Normorphothebaine derivatives: synthesis of an aporphine nitrogen mustardThe Journal of Organic Chemistry, 1977