Bioorthogonal late-stage diversification of structurally complex peptides bears enormous potential for drug discovery and molecular imaging. Despite major accomplishments, these strategies heavily rely on noble-metal catalysis. Herein, we report on a manganese(I)-catalyzed peptide C─H hydroarylation that enabled the stitching of peptidic and sugar fragments, under exceedingly mild and racemization-free conditions. This convergent approach represents an atom-economical alternative to traditional iterative peptide synthesis. The robustness of the manganese(I) catalysis regime is reflected by the full tolerance of a plethora of sensitive functional groups. Our strategy enabled an expedient access to challenging cyclic peptides by a modular late-stage macrocyclization of structurally complex peptides.

结构复杂肽的生物正交后期多样化在药物发现和分子成像方面具有巨大潜力。尽管取得了重大成就，但这些策略在很大程度上依赖于贵金属催化。在此，我们报道了一种锰 (I) 催化的肽 C─H 氢化反应，它能够在极其温和且无外消旋的条件下缝合肽和糖片段。这种收敛方法代表了传统迭代肽合成的原子经济替代方案。锰 (I) 催化体系的稳健性反映在对过多敏感官能团的完全耐受性上。我们的策略通过结构复杂肽的模块化后期大环化，能够方便地获得具有挑战性的环肽。