The First Example of the Stereoselective Synthesis of 7β-Carbamoyl-4,5α-epoxymorphinan via a Novel and Reactive γ-Lactone
The First Example of the Stereoselective Synthesis of 7β-Carbamoyl-4,5α-epoxymorphinan via a Novel and Reactive γ-Lactone
复制标题
通过新型反应性 γ-内酯立体选择性合成 7β-氨基甲酰基-4,5α-环氧吗啡喃的第一个实例
DOI：
10.1248/cpb.52.747
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发表时间：
2004
影响因子：
1.7
通讯作者：
H. Nagase
中科院分区：
文献类型：
--
作者：
H. Fujii;Noriyuki Hirano;H. Uchiro;K. Kawamura;H. Nagase
在1,8-重氮杂环[5.4.0]十一-7-烯（DBU）和胺的存在下，在回流条件下，通过一种新的反应性γ -内酯7，以7-羧酸中间体3为原料，立体选择性合成了7-氨基甲酰-4,5 - α -环氧吗啡酮5。这是立体选择性合成7 -取代4,5 - α -环氧吗啡酮的第一个例子。结果表明：1)7 -羧酸酯3的外映化，2)7 -羧酸酯6的分子内酯化，3)生成-内酯7的氨解反应。分离的反应性γ -内酯7在室温下与烯丙胺进行氨解，在NaBH(4)存在下与甲醇进行醇解。-内酯7可以作为制备7 -取代的4,5 α -环氧吗啡酮的有用中间体，这将是有效的选择性δ阿片受体配体。7 -羧酸盐3经7 -羧酸催化合成了7 -氨基甲酰-4,5 -环氧吗啡酮9。
7beta-Carbamoyl-4,5alpha-epoxymorphinans 5 were stereoselectively synthesized from the 7alpha-carboxylate intermediate 3 in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and amines under reflux conditions in mesitylene via a novel and reactive gamma-lactone 7. These were the first examples of the stereoselective syntheses of 7beta-substituted 4,5alpha-epoxymorphinans. The mechanism of the reaction process was elucidated as follows: 1) epimerization of 7alpha-carboxylate 3, 2) intramolecular lactonization of 7beta-carboxylate 6, and 3) aminolysis of the resultant gamma-lactone 7. The aminolysis of the isolated reactive gamma-lactone 7 with allylamine and the alcoholysis with MeOH in the presence of NaBH(4) proceeded at room temperature. The gamma-lactone 7 can be a useful intermediate for the preparation of 7beta-substituted 4,5alpha-epoxymorphinans that would be potent selective delta opioid receptor ligands. The stereoselective syntheses of the 7alpha-carbamoyl-4,5alpha-epoxymorphinans 9 from 7alpha-carboxylate 3 via 7alpha-carboxylic acid were also successful.
DOI：
10.5860/choice.42-5868
发表时间：
1995
期刊：
--
影响因子：
--
作者：
A. Katritzky;O. Meth–Cohn;C. Rees
通讯作者：
A. Katritzky;O. Meth–Cohn;C. Rees