S-Heteroarylation of Cysteines

doi:10.6023/cjoc202506011

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (1): 189-198.DOI: 10.6023/cjoc202506011 Previous Articles Next Articles

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半胱氨酸的硫杂芳基化反应

张鑫, 李飞, 周晨星, 霍聪德^*()

西北师范大学化学化工学院兰州 730070

收稿日期:2025-06-05 修回日期:2025-08-13 发布日期:2025-09-11
基金资助:
国家自然科学基金(22271234)

S-Heteroarylation of Cysteines

Xin Zhang, Fei Li, Chenxing Zhou, Congde Huo^*()

College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou 730070

Received:2025-06-05 Revised:2025-08-13 Published:2025-09-11
Contact: * E-mail: huocongde@nwnu.edu.cn
Supported by:
National Natural Science Foundation of China(22271234)

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Abstract

A new method for S-heteroarylation of cysteine derivatives using affordable, readily available chlorinated hetero- aromatic compounds has been proposed. The reaction proceeds via nucleophilic aromatic substitution (S_NAr) under mild conditions and simple operation, exhibiting excellent tolerance to various functional groups and high chemical selectivity. The results of substrate scope investigation demonstrated that A wide range of substrates, including different N-protected cysteine derivatives, cysteine-containing peptides, and various chlorinated heteroaryl compounds, could be efficiently transformed via this protocol to afford the desired products in good yields. Scale-up experiments confirmed the practicality and eco-friendliness of this protocol. Overall, this strategy offers an efficient and selective approach to modify cysteine and other thiols under mild conditions with broad potential applications in protein modification and biomolecular labeling.

Key words: cysteine, heteroarylation, peptide

Cite this article

Xin Zhang, Fei Li, Chenxing Zhou, Congde Huo. S-Heteroarylation of Cysteines[J]. Chinese Journal of Organic Chemistry, 2026, 46(1): 189-198.

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References 30

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Entry	Change from the standard conditions	Yield^b/%
1	None	93
2	w/o base	0
3	DMSO instead of MeCN	70
4	DMA instead of MeCN	75
5	ⁱPrOH instead of MeCN	85
6	MeCN/H₂O (V∶V=1∶1)	49
7	MeCN/H₂O (V∶V=2∶1)	60
8	MeCN/PBS (V∶V=1∶1)	40
9	Na₂CO₃ instead of K₂CO₃	17
10	K₃PO₄ instead of K₂CO₃	89
11	DIPEA instead of K₂CO₃	90

Entry	Change from the standard conditions	Yield^b/%
1	None	93
2	w/o base	0
3	DMSO instead of MeCN	70
4	DMA instead of MeCN	75
5	ⁱPrOH instead of MeCN	85
6	MeCN/H₂O (V∶V=1∶1)	49
7	MeCN/H₂O (V∶V=2∶1)	60
8	MeCN/PBS (V∶V=1∶1)	40
9	Na₂CO₃ instead of K₂CO₃	17
10	K₃PO₄ instead of K₂CO₃	89
11	DIPEA instead of K₂CO₃	90

半胱氨酸的硫杂芳基化反应

S-Heteroarylation of Cysteines

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References 30

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