Photocatalytic Decarboxylation of Carboxylic Acids to Construct Unnatural Amino Acids and Peptides-Containing...

Unnatural amino acids are fundamental building blocks in drug discovery, as their structural diversity critically influences both biological activity and pharmacokinetic properties. Although the piperidine ring is widely prevalent as a privileged scaffold in approved drugs, efficient methodologies for constructing piperidine-containing unnatural amino acids remain underdeveloped. In this study, we report a visible-light-driven decarboxylative conjugate addition reaction that utilizes piperidine carboxylic acids as radical precursors and dehydroalanine derivatives as radical acceptors, enabling the efficient synthesis of piperidine-incorporated unnatural amino acids. This protocol features mild conditions, broad substrate scope, and avoids preactivation steps, demonstrating excellent atom economy and functional group tolerance. The method provides a concise and efficient synthetic platform for the construction of piperidine-based unnatural amino acid libraries and the late-stage modification of peptides, holding significant promise for applications in innovative drug discovery.