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Synthetic methodology

Amino amide assembly

Nature Chemistry volume 15, pages 597–598 (2023)Cite this article

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Enantioenriched β-amino acid derivatives are attractive synthetic targets, considering the significance of these motifs in medicinal and material chemistry. Now, using ambiphilic ynamides as two-carbon synthons in a four-component reaction, three classes of β-amino amides with well-defined stereocentres can be accessed.

Optically active β-amino acid derivatives are the building blocks of many important pharmaceuticals. These motifs are commonly found in natural products, biomimetic polymers and peptidomimetics1,2. Their incorporation could improve the binding affinity and metabolic resistance of drugs, or confer unique conformations to design new materials. The asymmetric Mannich reaction, which forges a carbon–carbon bond between imines and enolizable carbonyl compounds, presents a straightforward route to prepare β-amino carbonyl compounds. However, the weak acidity of the α-C–H bond could hinder the formation of enolates from carboxyl derivatives such as esters and amides. Therefore, special amide substrates, like α-CF3 7-azaindoline acetamide, or pregenerated metal or metalloid enolates are needed to construct β-amino amides efficiently using this method3,4. Now, writing in Nature Chemistry, Bin Tan, Shao-Hua Xiang and co-workers introduce a strategically different approach that bypasses this reactivity limitation to construct β-amino amides5.

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Fig. 1: Modular synthesis of amino amides.

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Authors and Affiliations

  1. College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China

    Sunliang Cui & Linwei Zeng

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  1. Sunliang Cui
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  2. Linwei Zeng
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Correspondence to Sunliang Cui.

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The authors declare no competing interests.

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Cui, S., Zeng, L. Amino amide assembly. Nat. Chem. 15, 597–598 (2023). https://doi.org/10.1038/s41557-023-01182-5

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