通过协同催化的仲酰胺单元n -烷基化对寡肽的选择性醇解

IF 2.1 3区化学 Q2 CHEMISTRY, ORGANIC

Tetrahedron Pub Date : 2025-05-09 DOI:10.1016/j.tet.2025.134685

Yuankai Wang , Cunyuan Zhao , Masayuki Wasa

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引用次数: 0

摘要

我们披露了一个一锅两步方案的位置选择性切割寡肽内的C-N键。我们证明，利用Sc(OTf)3和Barton's碱的协同作用，可以实现寡肽特定仲酰胺单元的n -烷基化。所得到的叔酰胺由于位阻因素而“扭曲”；其C-N键因酰胺共振的破坏而减弱。因此，当寡肽衍生物进行Brønsted酸介导的醇解时，只有n -烷基化残基进行C-N键裂解以产生酯和胺，而其仲酰胺保持完整。研究旨在阐明影响所观察到的位点选择性的因素。

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Site-selective alcoholysis of oligopeptides through N-alkylation of a secondary amide unit by cooperative catalysis

We disclose a one-pot two-step protocol for site-selective cleavage of C–N bonds within oligopeptides. We demonstrate that by exploiting the cooperative functions of Sc(OTf)₃ and Barton's base, N-alkylation of the oligopeptide's specific secondary amide unit can be achieved. The resulting tertiary amide is “twisted” due to steric factors; its C–N bond is weakened by the disruption of amide resonance. Thus, when the oligopeptide derivative is subjected to Brønsted acid-mediated alcoholysis, only the N-alkylated residue undergoes C–N bond cleavage to afford an ester and an amine, while its secondary amides remain intact. Investigations aimed at elucidating the factors that influence the observed site-selectivity are described.

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来源期刊

Tetrahedron 化学-有机化学

CiteScore

3.90

自引率

4.80%

发文量

439

审稿时长

34 days

期刊介绍： Tetrahedron publishes full accounts of research having outstanding significance in the broad field of organic chemistry and its related disciplines, such as organic materials and bio-organic chemistry. Regular papers in Tetrahedron are expected to represent detailed accounts of an original study having substantially greater scope and details than that found in a communication, as published in Tetrahedron Letters. Tetrahedron also publishes thematic collections of papers as special issues and ''Reports'', commissioned in-depth reviews providing a comprehensive overview of a research area.