Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Tammannstrasse 2, 37077, Göttingen, Germany.
Angew Chem Int Ed Engl. 2017 Feb 1;56(6):1576-1580. doi: 10.1002/anie.201609631. Epub 2017 Jan 11.
Methods for the chemoselective modification of amino acids and peptides are powerful techniques in biomolecular chemistry. Among other applications, they enable the total synthesis of artificial peptides. In recent years, significant momentum has been gained by exploiting palladium-catalyzed cross-coupling for peptide modification. Despite major advances, the prefunctionalization elements on the coupling partners translate into undesired byproduct formation and lengthy synthetic operations. In sharp contrast, we herein illustrate the unprecedented use of versatile ruthenium(II)carboxylate catalysis for the step-economical late-stage diversification of α- and β-amino acids, as well as peptides, through chemo-selective C-H arylation under racemization-free reaction conditions. The ligand-accelerated C-H activation strategy proved water-tolerant and set the stage for direct fluorescence labelling as well as various modes of peptide ligation with excellent levels of positional selectivity in a bioorthogonal fashion. The synthetic utility of our approach is further demonstrated by twofold C-H arylations for the complexity-increasing assembly of artificial peptides within a multicatalytic C-H activation manifold.
化学选择性修饰氨基酸和肽的方法是生物分子化学中的强大技术。除其他应用外，它们还能够实现人工肽的全合成。近年来，利用钯催化的交叉偶联进行肽修饰获得了显著的进展。尽管取得了重大进展，但偶联伙伴上的预官能化元素会导致不需要的副产物形成和冗长的合成操作。与此形成鲜明对比的是，我们在此展示了多功能钌（II）羧酸酯催化在无外消旋反应条件下通过化学选择性 C-H 芳基化反应对 α-和 β-氨基酸以及肽进行分步经济性晚期多样化的前所未有的用途。配体加速的 C-H 活化策略被证明耐水性，并为直接荧光标记以及各种肽连接模式奠定了基础，这些模式以生物正交的方式具有优异的位置选择性。我们的方法的合成实用性通过在多催化 C-H 活化中进行双重 C-H 芳基化反应进一步得到证明，以增加人工肽的复杂性组装。
