Synthesis and Characterization of a Novel Diels - Alder Adduct of Codeine.
Synthesis and Characterization of a Novel Diels - Alder Adduct of Codeine.
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可待因新型 Diels-Alder 加合物的合成和表征。
DOI：
10.1002/hlca.200900234
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发表时间：
2010
影响因子：
1.8
通讯作者：
Coop,Andrew
中科院分区：
文献类型：
--
作者：
Cunningham,ChristopherW;Hom,Kellie;Acharya,Chayan;Wilks,Angela;MackerellJr,AlexanderD;Coop,Andrew
将Diels-Alder反应应用于4，5-环氧吗啉类阿片类药物，在C(7)C(8)上生成了一种新的芳香族环加成物：硫代8的热解裂解生成了反应性的二烯奎诺二甲烷7，它与可待因(11)发生了良好的缩合反应，但与可待酮(9)或14-羟基可待酮(10)不发生缩合反应，生成了具有(7R，8R)构型的四氢萘加成物12(SCHEP)。通过一维和二维核磁共振实验确定了环加合物的构型。通过量子力学计算研究了这些可待因衍生物的意外反应性，并确定了6-酮和14-羟基的空间效应可能通过提高它们各自过渡态的分子能量来阻止缩合。
TheDiels–Alderreaction was applied to 4,5‐epoxymorphinan opioids to generate a novel aromatic cycloadduct at C(7)C(8): Thermolytic cleavage of sultine8produced the reactive dieneo‐quinodimethane7which condensed favorably with codeine (11), but not with codeinone (9) or 14‐hydroxycodeinone (10), producing the desired tetrahydronaphtho adduct12with (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.