Concise Synthesis of Substituted Quinolizin-4-ones by Ring-Closing Metathesis
Concise Synthesis of Substituted Quinolizin-4-ones by Ring-Closing Metathesis
复制标题
DOI：
10.1002/ejoc.201402648
复制
发表时间：
2014-09-01
影响因子：
2.8
通讯作者：
Spring, David R.
中科院分区：
文献类型：
--
作者：
Alanine, Thomas A.;Galloway, Warren R. J. D.;Spring, David R.
4H-喹诺酮-4-酮支架具有重要的药用价值。这种杂环结构被预测具有诱人的物理化学性质，并存在于各种生物活性分子中。尽管有这些有趣的特征，4H-喹啉-4-酮在目前的小分子筛选文库中很大程度上是表达不足的，因此，这种支架的研究一直很少。在此，报道了一种新的方法来合成这些稀有的、具有生物意义的4H-喹啉-4-酮。这条模块化路线包括6-卤代-2-吡啶酮的区域选择性N-烷基化，然后是Stille交叉偶联、闭环歧化和钯催化的脱氢反应序列。这种方法以良好的产率提供了目标化合物，并允许获得使用其他合成策略难以实现的不寻常的取代模式。
The 4H-quinolizin-4-one scaffold is of significant pharmaceutical interest. This heterocyclic structure is predicted to have attractive physico-chemical properties and is present in a variety of biologically active molecules. Despite these interesting characteristics, 4H-quinolizin-4-ones are largely under-represented in current small molecule screening libraries, and, therefore, this scaffold has been poorly investigated. Herein, a new strategy is reported for the syntheses of these rare and biologically interesting 4H-quinolizin-4-ones. This modular route involves the regioselective N-alkylation of 6-halo- 2-pyridones followed by a Stille cross-coupling, ring-closing metathesis, and palladium-catalyzed dehydrogenation reaction sequence. This method furnishes the target compounds in good yields and allows for access to unusual substitution patterns that are difficult to achieve by using other synthetic strategies.