Ugi four-component reactions (U-4CRs) are widely recognized as being highly efficient for the synthesis of pseudopeptides. However, the products of these reactions are not so interesting as drug candidates because they are not conformationally restricted enough for a potent interaction with biological targets. One possible way to overcome this problem is to replace amine and oxo components in the U-4CRs with cyclic imines in so-called Joullié−Ugi three-component reactions (JU-3CRs). This approach provides a robust single-step route to peptide moieties connected to N-heterocyclic motifs that are found as core skeletons in many natural products and pharmaceutical compounds. JU-3CRs also provide much better diastereoselectivity than their four-component analogues. We survey here the redesign of many synthetic routes for the efficient preparation of a wide variety of three-, five-, six-, and seven-membered heterocyclic compounds connected to the peptide backbone. Additionally, in the Ugi reactions based on the cyclic imines, α-acidic isocyanides, or azides can be replaced with normal isocyanides or acids, respectively, leading to the synthesis of N-heterocycles attached to oxazoles or tetrazoles, which are of great pharmaceutical significance. This Review includes all research articles related to Ugi reactions based on the cyclic imines to the year 2020 and will be useful to chemists in designing novel synthetic routes for the synthesis of individual and combinatorial libraries of natural products and drug-like compounds.

中文翻译：

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Ugi和Ugi型反应中的环亚胺。

Ugi四组分反应（U-4CR）被公认为对合成伪肽非常有效。但是，这些反应的产物并不像候选药物那样有趣，因为它们的构象限制不足以与生物靶标有效相互作用。解决此问题的一种可能方法是在所谓的Joullié-Ugi三组分反应（JU-3CR）中用环状亚胺取代U-4CR中的胺和氧代组分。该方法为连接至N的肽部分提供了可靠的一步法-杂环基序，在许多天然产物和药物化合物中被视为核心骨架。JU-3CR还提供比其四组分类似物更好的非对映选择性。我们在这里调查了许多合成路线的重新设计，以有效制备连接至肽骨架的多种三元，五元，六元和七元杂环化合物。另外，在基于环状亚胺的Ugi反应中，α-酸性异氰酸酯或叠氮化物可以分别用正异氰酸酯或酸替代，从而导致N的合成-杂环与恶唑或四唑连接，具有重要的药学意义。这篇综述包括所有与基于环亚胺的Ugi反应有关的研究论文，到2020年，这将对化学家设计新颖的合成途径用于合成天然产物和类药物化合物的单个和组合文库有用。