title: Synthesis and Characterization of a Novel Diels - Alder Adduct of Codeine.
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 (7R,8R) 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.
authors: University of Maryland, School of Pharmacy, Department of Pharmaceutical Sciences, 20 Penn Street, Baltimore, MD 21201, USA.
authors: Christopher W
authors: CW
authors: Cunningham
authors: Kellie
authors: K
authors: Hom
authors: Chayan
authors: C
authors: Acharya
authors: Angela
authors: A
authors: Wilks
authors: Alexander D
authors: AD
authors: Mackerell
authors: Andrew
authors: A
authors: Coop
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