Synthesis of Novel Morphinans From Thebaine

McDougall, Duncan Campbell (1981) Synthesis of Novel Morphinans From Thebaine. PhD thesis, University of Glasgow.

Abstract

The synthesis of codeinone enol ethers from thebaine, via acetals of 14beta-bromocodeinone, has been successfully carried out. These enol ethers have, in turn, been converted into 6-alkoxy-6-desmethoxy-19-alkylthevinols, which have been shown to be analgesics of potency comparable to that of morphine. The reduction of 14beta-bromocodeinone dimethyl acetal to thebaine has been investigated, and it has been proved that the reaction leads to highly selective loss of the 6B-methoxy group. The synthesis of 14beta-alkylthionorcodeinones has been accomplished by reaction of N-t-butoxycarbonylnorthebaine with sulphenyl chlorides, followed by deprotection. Thebaine itself does not undergo sulphenyl-ation under these conditions and has proved unreactive towards other sulphur reagents. However, 14beta-(2-phenylethyl)thiocodeinone has been produced by N-methylation of the corresponding nor base. These alkylthiocodeinone derivatives have been tested for analgesic potency and have been found to be analgesics of moderate to high activity. Some reactions of the alkylthionorcodeinones, including their oxidation to 14-alkylsulphonylnorcodeinones, have been investigated. Thebaine has been found to react with certain sulphenyl chlorides in the presence of triethylamine to give Diels-Alder type adducts, whose formation is consistent with generation of thioaldehydes in situ. The formation of these adducts, the first of their kind, and some of their reactions have been investigated.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Organic chemistry
• Date of Award: 1981
• Depositing User: Enlighten Team
• Unique ID: glathesis:1981-77174
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 14 Jan 2020 09:17
• Last Modified: 14 Jan 2020 09:17
• URI: https://theses.gla.ac.uk/id/eprint/77174