Synthesis and Characterization of a Novel Diels–Alder Adduct of Codeine

✍ Scribed by Christopher W. Cunningham; Kellie Hom; Chayan Acharya; Angela Wilks; Alexander D. MacKerell Jr.; Andrew Coop

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: German
• Weight: 181 KB
• Volume: 93
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.200900234

✦ Synopsis

Abstract

The Diels–Alder reaction was applied to 4,5‐epoxymorphinan opioids to generate a novel aromatic cycloadduct at C(7)C(8): Thermolytic cleavage of sultine 8 produced the reactive diene o‐quinodimethane 7 which condensed favorably with codeine (11), but not with codeinone (9) or 14‐hydroxycodeinone (10), producing the desired tetrahydronaphtho adduct 12 with (7__R__,8__R__) geometry (Scheme). The configuration of the cycloadduct was determined by 1D‐ and 2D‐NMR experiments. The unanticipated reactivity of these codeine derivatives was investigated by quantum‐mechanical calculations, and it was determined that steric effects of the 6‐keto and 14‐hydroxy group likely precluded condensation by raising the molecular energy of their respective transition states.