Modular assembly of chiral amino acid derivatives and peptides from commonly available feedstocks
α-Amino acids are fundamental components of proteins and natural molecules, with non-natural variants highly valued in both academia and industry for their ability to tune chemical, physical, and pharmaceutical properties. Herein, we report a photoredox-catalyzed protocol for the synthesis of optically active α-amino amides from readily available aldehydes, amines, and formamides. A dual catalytic system combining a chiral sodium phosphate with tetrabutylammonium decatungstate (TBADT) under visible light enables this transformation. The process achieves high enantioselectivity and allows two-step conversion to free amino acids without significant racemization. Consequently, diverse, synthetically useful structures-including β-branched and α,β-diamino acid derivatives, glycosylated amino acids, isotopically labeled compounds (deuterium and <sup>15</sup>N), and peptides-have been rapidly constructed. Flow chemistry further broadens substrate tolerance and eliminates prefunctionalization steps. Here, we show that leveraging TBADT-driven carbamoyl radical generation and chiral catalysis provides a practical route to diverse chiral scaffolds, thereby advancing peptide synthesis and drug discovery.
Authors
- Wan-Yu Wang
- Zhi-Yong Han
- Liu-Zhu Gong
- Wei-Wei Ding
- Zhi-Yuan He
Institutions
- University of Science and Technology of China (CN)
- Hefei National Center for Physical Sciences at Nanoscale (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-12-30
- DOI
- https://doi.org/10.1038/s41467-025-68073-w
- Citations
- 1
- Primary Topic
- Radical Photochemical Reactions
- Type
- article
- Field-Weighted Citation Impact
- 0.94
Funders
- National Natural Science Foundation of China