Late-Stage Functionalization and Diversification of Peptides by Internal Thiazole-Enabled Palladium-Catalyzed C(sp3)-H Arylation
Late-Stage Functionalization and Diversification of Peptides by Internal Thiazole-Enabled Palladium-Catalyzed C(sp3)-H Arylation
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通过内部噻唑钯催化的 C(sp3)→H 芳基化对肽进行后期功能化和多样化
DOI：
10.1021/acscatal.1c05030
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发表时间：
2021-12-17
期刊：
影响因子：
12.9
通讯作者：
Wang, Huan
中科院分区：
文献类型：
--
作者：
Bai, Zengbing;Chen, Qingqing;Wang, Huan
通过后期C-H活化对肽进行修饰是构建具有扩大的结构多样性的生物活性肽模拟物文库用于药物发现的新兴策略。在主链中具有噻唑基序的肽作为酰胺替代物通常表现出改善的生物活性和生物稳定性。然而，合成这类具有结构多样性的化合物的方法是有限的。在这里，我们报告了一个高度通用的战略发展后期钯催化的C（sp（3））-H芳基化的肽。该方案利用肽骨架中的噻唑基序作为内部导向基团，并允许肽侧链中β-C（sp（3））-H和γ-C（sp（3））-H键的区域和位点选择性芳基化。该方法的高度生物相容性使肽与各种芳基供体、生物分子和荧光团官能化和连接，为有效构建具有特征骨架噻唑单元的肽文库奠定了基础。
Modification of peptides via late-stage C-H activation is an emerging strategy to construct bioactive peptidomimetic libraries with expanded structural diversity for drug discovery. Peptides with thiazole motifs in the backbone as amide surrogates often exhibit improved bioactivity and biostability. However, methods to synthesize this class of compounds with structural diversity are limited. Here, we report the development of a highly versatile strategy for late-stage palladium-catalyzed C(sp(3))-H arylation of peptides. This protocol utilizes the thiazole motifs in the peptide backbone as internal directing groups and allows the regio- and site-selective arylation of beta-C(sp(3))-H and gamma-C(sp(3))-H bonds in peptide side chains. The high biocompatibility of this method to functionalize and ligate peptides with a variety of aryl donors, biomolecules, and fluorophores sets the stage for efficient construction of peptide libraries with featured backbone thiazole units.