Cai Chuangxu, Wang Feifei, Xiao Xiuyun, Sheng Wangjian, Liu Shu, Chen Jun, Zheng Jie, Xie Ran, Bai Zengbing, Wang Huan
State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center of Nanjing University, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
Chem Commun (Camb). 2022 Apr 14;58(31):4861-4864. doi: 10.1039/d1cc06764h.
Peptides containing thiazole fragments represent a large group of bioactive compounds with potential medicinal applications. However, methods for efficient synthesis of these compounds with structural diversity are limited. Herein, we report a method for modification and macrocyclization of thiazole-containing peptides through palladium-catalyzed δ-C(sp)-H olefination. In this protocol, the thiazole and neighboring amide bonds act as directing groups, which allows site-specific olefination of phenylalanine, tryptophan and tyrosine residues. This chemistry exhibits broad substrate scope and provides facile access to peptide-peptide conjugates and peptide macrocycles. Our results highlight the potency and applicability of thiazole motifs in promoting Pd-catalyzed functionalization of peptides.
含有噻唑片段的肽代表了一大类具有潜在医学应用价值的生物活性化合物。然而，高效合成这些具有结构多样性的化合物的方法有限。在此，我们报道了一种通过钯催化的δ-C(sp)-H烯基化反应对含噻唑肽进行修饰和大环化的方法。在该方案中，噻唑和相邻的酰胺键作为导向基团，使得苯丙氨酸、色氨酸和酪氨酸残基能够进行位点特异性烯基化反应。这种化学方法具有广泛的底物范围，并能方便地获得肽-肽缀合物和肽大环化合物。我们的结果突出了噻唑基序在促进钯催化的肽功能化反应中的潜力和适用性。
