Modular assembly of chiral amino acid derivatives and peptides from commonly available feedstocks
Year: 2025
Type: article
Abstract: 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 15N), 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. α-Amino acids are fundamental components of proteins and natural molecules, with nonnatural variants valued in both academia and industry for their ability to tune chemical, physical, and pharmaceutical properties. Herein, the authors report a photoredox-catalyzed protocol for the synthesis of optically active α-amino amides from readily available aldehydes, amines, and formamides.
Source: Nature Communications
Authors: Wei-Wei Ding, Zhi-Yuan He, Wan-Yu Wang, Zhi-Yong Han, Liu-Zhu Gong
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: G4890951106, G6721630351
OpenAlex ID: W7117530855