138916-45-7Relevant academic research and scientific papers
Synthesis of 20-Alkyl-8-thiathevinols. Opiate Agonists Derived from 8-Thiathevinone, the Cycloadduct of Thebaine and 2-Oxopropanethial
Kirby, Gordon W.,Sclare, Alastair D.
, p. 2329 - 2338 (2007/10/02)
The cycloadduct 7 has been prepared from thebaine 1 and the transient thioaldehyde EtO2C-CHS formed in situ from the Bunte salt EtO2C-CH2SSO3Na.The thermal isomerisation of the adduct 7 to give the regioisomer 8 has been reinvestigated.Prolonged heating gave an equilibrium mixture of the adduct 8 and the major, rearrangement product 9.Base-catalysed epimerisation of the adduct 7 gave the 7β-isomer 11, believed to be a transient co-product in the thermal isomerisation of the original adduct 7.Similarly, thebaine 1 and 2-oxopropanethial 18, generated from either the Bunte salt MeCOCH2SSO3Na or the thiotosylate 16 and triethylamine, gave the cycloadduct 8-thiathevinone 3, the sulphur analogue of thevinone 2, the known cycloadduct of thebaine and but-3-en-2-one. 8-Thiathevinone 3 isomerised thermally to give the corresponding 7-thia-regioisomer. 8-Thiathevinone 3 has been converted with Grignard reagents into a series of (20R)- and (20S)-20-alkyl-8-thiathevinols 5.The reactions were not stereoselective, unlike those of thevinone 2, and the tertiary alcohols 5 were accompanied by the secondary alcohols 19 and 20, products of 'Grignard reduction'.The analgesic potency, in guinea-pig ileum preparations, of the alkylthiathevinols 5 depended upon the C-20 configuration and the alkyl chain length.The (20R)-epimers were the more potent, the maximum potency being observed for the (20R)-20-pentyl derivative 5h, which was equipotent with N-normorphine.Generally, the thiathevinols were much less potent than the corresponding thevinols. 8-Thiathevinone 3 also reacted with alkyllithium reagents to give (20R)-alkylthiathevinols, but the reactions were accompanied by a base-catalysed rearrangement to give the ketoacetal 27.
