Robust Whole‐Cell‐Based Chemoenzymatic Synthesis of Site‐Selective Deuterated α‐Hydroxy Acids and α‐Amino Acids

Abstract Deuterated hydroxyl acids and amino acids have been widely utilized in life science, biochemistry and drug development. Site‐selective and stereoselective synthesis of deuterated hydroxyl acids and amino acids remains a significant challenge. Here, we report the development of a robust whole‐cell‐based chemoenzymatic platform for the synthesis of deuterated hydroxyl acids and amino acids from off‐the‐shelf aldehydes in high yields with excellent selectivities and levels of deuteration. The platform delivers products with diverse scaffolds and deuteration patterns, as well as broad scopes with both aromatic and aliphatic side chains. The application of the platform was demonstrated by the concise synthesis of a deuterium‐containing antiparkinson's disease candidate. This platform provides a concrete foundation for accessing amino acid isotopologs for potential applications in research and drug discovery and development.