Photocatalytic Radical-Mediated Synthesis of Unnatural α-Amino Acids from Heteroaryl Aldehydes

doi:10.6023/cjoc202507030

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (1): 215-224.DOI: 10.6023/cjoc202507030 Previous Articles Next Articles

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光催化合成含氮杂芳环非天然氨基酸

任钶^†, 张光露^†, 牛轶凡, 王晓萌, 陈灿玉^*(), 蒋敏^*()

杭州师范大学材料与化学化工学院杭州 311121

收稿日期:2025-07-21 修回日期:2025-08-28 发布日期:2025-09-11
作者简介:
^† 共同第一作者
基金资助:
杭州师范大学国内访问学者(4095C5022521106); 杭州师范大学教师发展(FX2024069)

Photocatalytic Radical-Mediated Synthesis of Unnatural α-Amino Acids from Heteroaryl Aldehydes

Ke Ren, Guanglu Zhang, Yifan Niu, Xiaomeng Wang, Canyu Chen^*(), Min Jiang^*()

School of Material, Chemistry and Chemical Engineering, University of Hangzhou Normal University, Hangzhou 311121

Received:2025-07-21 Revised:2025-08-28 Published:2025-09-11
Contact: * E-mail: chency@hznu.edu.cn; jiang-m18@hznu.edu.cn
About author:
^† The authors contributed equally to this work
Supported by:
Domestic Visiting Fellows Program of Hangzhou Normal University(4095C5022521106); Teachers’ Professional Development Program of Hangzhou Normal University(FX2024069)

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Abstract

Non-natural α-amino acids (α-AAs) are pivotal in drug and catalysis, yet their synthesis remains challenges. A photocatalytic strategy for the direct construction of N-heteroaryl-containing α-AAs from heteroaryl aldehydes via acyl radical intermediates is reported. This method exhibits exceptional functional group tolerance and enables late-stage diversification of peptides and carbonyl-group derivatization. Mechanistic studies confirm a radical-based pathway, while applications in peptide modification highlight its utility in bioorganic chemistry.

Key words: photocatalytic, non-natural amino acids, heteroaryl aldehydes, acyl radical, electron paramagnetic resonance

Cite this article

Ke Ren, Guanglu Zhang, Yifan Niu, Xiaomeng Wang, Canyu Chen, Min Jiang. Photocatalytic Radical-Mediated Synthesis of Unnatural α-Amino Acids from Heteroaryl Aldehydes[J]. Chinese Journal of Organic Chemistry, 2026, 46(1): 215-224.

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Fig. & Tab. 6

Scheme 1. (a) Representative samples of valuable α-AAs; (b) Activation of aldehydes (previous works); (c) Photocatalytic activation of heteroaryl formaldehyde to synthesis nonnatural α-amino acids

Entry	Deviation from standard conditions	Yield^b/%

Table 1. Optimization of the reactiona

Table 2. Scope of aryl aldehydesa

Scheme 2. (a) Synthetic applications; (b) Late-stage reduction; (c) Gram-scale synthesis

Scheme 3. Mechanism studies

Scheme 4. Proposed mechanism

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光催化合成含氮杂芳环非天然氨基酸

Photocatalytic Radical-Mediated Synthesis of Unnatural α-Amino Acids from Heteroaryl Aldehydes

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