Binary Catalytic Hydrogen/Deuterium Exchange of Free α‐Amino Acids and Derivatives

Abstract

AbstractThe increasing demand for deuterium‐labeled amino acids and derivatives has heightened interest in direct hydrogen/deuterium exchange reactions of free amino acids. Existing methods, including biocatalysis and metal catalysis, typically require expensive deuterium sources or excessive use of deuterium reagents and often struggle with site selectivity. In contrast, this binary catalysis system, employing benzaldehyde and Cs2CO3 in the presence of inexpensive D2O with minimal stoichiometric quantities, facilitates efficient hydrogen/deuterium exchange at the α‐position of amino acids without the need for protecting groups in the polar aprotic solvent DMSO. The process is highly compatible with most natural and non‐natural α‐amino acids and derivatives, even those with potentially reactive functionalities. This advancement not only addresses the cost and efficiency concerns of existing methods but also significantly broadens the applicability and precision of deuterium labeling in biochemical research.