Scalable thioarylation of unprotected peptides and biomolecules under Ni/photoredox catalysis†,Chemical Science

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Scalable thioarylation of unprotected peptides and biomolecules under Ni/photoredox catalysis†
Chemical Science ( IF 7.6 ) Pub Date : 2017-11-13 00:00:00 , DOI: 10.1039/c7sc04292b
Brandon A. Vara _{1,

2,

3,

4,

5} , Xingpin Li _{1,

2,

3,

4,

5} , Simon Berritt _{1,

2,

3,

4,

5} , Christopher R. Walters _{1,

2,

3,

4,

5} , E. James Petersson _{1,

2,

3,

4,

5} , Gary A. Molander _{1,

2,

3,

4,

5}

Affiliation

Site-specific functionalization of unprotected native peptides and biomolecules remains a useful transformation in synthetic design and chemical biology, yet until recently, advancements in transition metal-catalyzed methods, which have prevailed in organic synthesis, have been relatively ineffective when applied to large and structurally complex biomolecules. Here, the mechanistically distinct, Ni/photoredox-catalyzed arylation of unprotected, native thiols (e.g., cysteine residues) is reported – a process initiated through a visible light-promoted, hydrogen atom transfer (HAT) event under ambient conditions. Sub-stoichiometric loadings of the dual-catalyst system (≤5 mol%) are employed, granting excellent site-specificity, broad substrate scope, and low chemical waste. Reaction scalability (from μg to grams) has been achieved through modest reagent adjustments, and high throughput experimentation (HTE) demonstrates the ease of reaction setup, enabling prompt screening of aryl halide coupling partners and conditions. Scores of thiol substrates and aryl entities were examined and effectively conjugated, suggesting further diverse, practical applications.

中文翻译：

Ni /光氧化还原催化下未保护的肽和生物分子的可扩展硫代芳基化作用†

未受保护的天然肽和生物分子的位点特异性功能化在合成设计和化学生物学中仍然是有用的转变，但是直到最近，有机合成中普遍使用的过渡金属催化方法的进步在应用于大型结构上时相对无效。复杂的生物分子。在这里，机理上独特的，未保护的天然硫醇（例如，Ni /光氧化还原催化的芳基化反应）（半胱氨酸残基）的报道–通过在环境条件下可见光促进的氢原子转移（HAT）事件启动的过程。采用双催化剂系统的亚化学计量负载（≤5mol％），具有出色的位点特异性，广泛的底物范围和较低的化学废料。通过适度的试剂调整，可以实现反应的可扩展性（从微克到克），并且高通量实验（HTE）证明了反应设置的简便性，从而可以快速筛选芳基卤化物偶联物和条件。硫醇底物和芳基实体的分数进行了检查，并有效地共轭，表明进一步多样化的实际应用。

更新日期：2017-11-13

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