Reactions of thebaine and 6-demethoxythebaine anions with carbonyl compounds; novel Diels-Alder adducts from 5β-substituted thebaines (chemistry of opium alkaloids, Part XXXIX)

✍ Scribed by R. H. Woudenberg; T. S. Lie; L. Maat

• Publisher: Elsevier Science
• Year: 2010
• Tongue: English
• Weight: 831 KB
• Volume: 112
• Category: Article
• ISSN: 0165-0513
• DOI: 10.1002/recl.19931121008

✦ Synopsis

Abstract

Reaction of the anions of thebaine and 6‐demethoxythebaine with 2‐propanone gave the 5β‐(dimethylmethanol)‐substituted analogues 3 and 5 and the isomeric C‐7‐substituted morphinan‐5,8‐dienes 4, 6 and 7, respectively. No reaction took place with methanal. Therefore, thebaine‐5β‐methanol (10) was prepared by reacting the anion with alkyl chloroformate followed by lithium aluminium hydride reduction. Diels‐Alder reaction of diene 10 with ethyl acrylate gave the 6α,14α‐ethenoisomorphinan 11. Of the morphinan‐6,8‐dienes 3 and 5, only diene 5 showed a reaction, namely rearrangement followed by cycloaddition with ethyl acrylate, yielding three adducts. The structure of the major adduct 13 was elucidated using 1D‐ and 2D‐NMR techniques and revealed an aporphine‐like structure. Furthermore, the conversion of 11 into a new etorphine analogue 16 was accomplished by treatment with methylmagnesium bromide followed by 3‐O‐demethylation.