Abstract

A short reaction pathway was devised to synthesize a library of artificial 18–27-membered macrocycles. The five-step reaction sequence involves ring opening of a cyclic anhydride with a diamine, esterification, coupling with an amino acid isocyanide, saponification, and, finally, macro-ring closure using an Ugi or, alternatively, a Passerini multicomponent reaction. Three out of the five steps allow for the versatile introduction of linker elements, side chains, and substituents with aromatic, heteroaromatic, and aliphatic character. The versatile pathway is described for 15 different target macrocycles on a mmol scale. Artificial macrocycles have recently become of great interest due to their potential to bind to difficult post-genomic targets.

A short reaction pathway was devised to synthesize a library of artificial 18–27-membered macrocycles. The five-step reaction sequence involves ring opening of a cyclic anhydride with a diamine, esterification, coupling with an amino acid isocyanide, saponification, and, finally, macro-ring closure using an Ugi or, alternatively, a Passerini multicomponent reaction. Three out of the five steps allow for the versatile introduction of linker elements, side chains, and substituents with aromatic, heteroaromatic, and aliphatic character. The versatile pathway is described for 15 different target macrocycles on a mmol scale. Artificial macrocycles have recently become of great interest due to their potential to bind to difficult post-genomic targets.

中文翻译：

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多组分反应简明合成大环化合物

摘要

设计了一条短反应途径来合成人工 18-27 元大环化合物库。五步反应顺序包括环酸酐与二胺的开环、酯化、与氨基酸异氰化物的偶联、皂化，最后使用 Ugi 或 Passerini 多组分反应进行大环闭合。五个步骤中的三个允许灵活地引入具有芳香族、杂芳香族和脂肪族特征的接头元件、侧链和取代基。该通用途径描述了 15 种不同的目标大环化合物（毫摩尔量级）。人工大环化合物最近引起了人们的极大兴趣，因为它们有可能与困难的后基因组目标结合。

设计了一条短反应途径来合成人工 18-27 元大环化合物库。五步反应顺序包括环酸酐与二胺的开环、酯化、与氨基酸异氰化物的偶联、皂化，最后使用 Ugi 或 Passerini 多组分反应进行大环闭合。五个步骤中的三个允许灵活地引入具有芳香族、杂芳香族和脂肪族特征的接头元件、侧链和取代基。该通用途径描述了 15 种不同的目标大环化合物（毫摩尔量级）。人工大环化合物最近引起了人们的极大兴趣，因为它们有可能与困难的后基因组目标结合。