College of Pharmaceutical Sciences, Zhejiang University of Technology, 310014, Hangzhou, P.R. China.
Angew Chem Int Ed Engl. 2022 Oct 10;61(41):e202206308. doi: 10.1002/anie.202206308. Epub 2022 Sep 8.
As the aromatic tryptophan (Trp) side chain plays a pivotal role in influencing the structure and function of peptides and proteins, it has become an attractive target for the late-stage modification of these important biomolecules. Herein, we report an electrochemical approach for late-stage functionalization of peptides containing a Trp side chain through manganese-catalyzed tandem radical azidation/heterocyclization. This electrochemical oxidative strategy provides access to azide-substituted tetrazolo[1,5-a]indole-containing peptides with broad functional group tolerance, high site selectivity, and good yields of products (up to 87 %) under mild buffer conditions. Moreover, the modified Trp-containing peptides bearing an azide functionality are promising building blocks, paving the way for the construction of various derivatives, such as "click" chemistry products.
由于芳香族色氨酸（Trp）侧链在影响肽和蛋白质的结构和功能方面起着关键作用，因此它已成为这些重要生物分子后期修饰的一个有吸引力的目标。在此，我们报告了一种电化学方法，用于通过锰催化的串联自由基叠氮化/杂环化来对含有 Trp 侧链的肽进行后期功能化。这种电化学氧化策略为含有叠氮基取代的四唑并[1,5-a]吲哚的肽提供了一种方法，在温和的缓冲条件下具有广泛的官能团容忍度、高的位点选择性和良好的产物收率（高达 87%）。此外，含有叠氮功能的修饰的 Trp 肽是很有前途的构建块，为构建各种衍生物（如“点击”化学产物）铺平了道路。
