Isocyanide-Based Multicomponent Reactions for the Synthesis of Heterocycles.
Isocyanide-Based Multicomponent Reactions for the Synthesis of Heterocycles.
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DOI：
10.3390/molecules21010019
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发表时间：
2015-12-23
期刊：
影响因子：
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通讯作者：
Majumdar S
中科院分区：
文献类型：
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作者：
Váradi A;Palmer TC;Notis Dardashti R;Majumdar S
多组分反应(MCRs)因其操作简便、原子效率高、产物种类繁多等优点而备受关注。MCRS可以用来获得各种杂环和高度功能化的支架，因此在全合成、药物发现和生物偶联方面已经成为无价的工具。传统的基于异氰化物的MCR利用外部亲核试剂攻击反应性的氮离子，该离子是亚胺和异氰化物反应中形成的关键中间体。然而，当具有多个亲核基团的反应物(双官能反应物)用于MCR时，硝化中间体可以被分子内的亲核攻击捕获而形成各种杂环。本文讨论了氮离子捕集技术和广泛应用的传统的异氰酸酯类化合物在药物设计中的应用。
Multicomponent reactions (MCRs) are extremely popular owing to their facile execution, high atom-efficiency and the high diversity of products. MCRs can be used to access various heterocycles and highly functionalized scaffolds, and thus have been invaluable tools in total synthesis, drug discovery and bioconjugation. Traditional isocyanide-based MCRs utilize an external nucleophile attacking the reactive nitrilium ion, the key intermediate formed in the reaction of the imine and the isocyanide. However, when reactants with multiple nucleophilic groups (bisfunctional reactants) are used in the MCR, the nitrilium intermediate can be trapped by an intramolecular nucleophilic attack to form various heterocycles. The implications of nitrilium trapping along with widely applied conventional isocyanide-based MCRs in drug design are discussed in this review.