Hutchins C W, Cooper G K, Pürro S, Rapoport H
J Med Chem. 1981 Jul;24(7):773-7. doi: 10.1021/jm00139a002.
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.
蒂巴因的6-去甲氧基类似物可通过异可待因及其亚磺酸酯从可待因轻松制备。这种二烯（7）很容易与乙烯基酮发生反应，生成6,14-乙烯基吗啡喃型的狄尔斯-阿尔德加合物。进一步反应可得到差向异构的19(R)-和19(S)-丁基-6-去甲氧基-7α-奥维诺醇（16）。药理测试表明，R非对映异构体具有高度镇痛作用，而S非对映异构体是一种效力低得多的激动剂，其效力和关系与相应的阿片派定系列相似。因此，6-甲氧基与叔醇之间的任何氢键都可被排除，因为它对差向异构奥维诺醇的活性或差异没有贡献。
