Shengdong Wang; Haoran Li; Yuwei Liu; Silin Zhang; Lei Ma; Zhongyi Zeng; Zhi Zhou; Hongtao Xu; Wei Yi
PREPRINT available at Research Square, 2024
https://doi.org/10.21203/rs.3.rs-4944895/v1

Abstract

The development of practical and selective deuterium incorporation strategies for building deuterated molecules, especially deuterium-labeled amino acids, has become an increasing focus in basic research, but still remains challenging. We herein report a bioinspired calcium(II)/HFIP-catalyzed site-selective modular reductive deuteration amination of simple keto acids/esters with amines by using d2-Hantzsch ester as the deuterium source, delivering N-α-deuterated amino acid motifs in a remarkable deuteration efficiency (>99 deuterated ratio) and with diverse functionality (>130 examples), for which various substrates, especially including amino acids, peptides, drug molecules and natural products bearing different substituted forms, was found to be well compatible. Besides, the application of this strategy in the on-DNA synthesis of DNA-tagged N-α-deuterated amino acids/peptides has been exemplified. The work provides an efficient and innovative solution for deuterated amino acid chemistry and should have a robust application potential in organic synthesis, medicinal chemistry and chemical biology.