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Synthesis and Characterization of a Novel Diels – Alder Adduct of Codeine
Author(s) -
Cunningham Christopher W.,
Hom Kellie,
Acharya Chayan,
Wilks Angela,
MacKerell Alexander D.,
Coop Andrew
Publication year - 2010
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200900234
Subject(s) - chemistry , adduct , steric effects , reactivity (psychology) , codeine , diene , diels–alder reaction , condensation , medicinal chemistry , stereochemistry , computational chemistry , photochemistry , organic chemistry , catalysis , morphine , medicine , natural rubber , alternative medicine , physics , pathology , pharmacology , thermodynamics
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.