Photoredox-Catalyzed Minisci-Type Acylation of Heterocyclic C-H Bonds with Amino Acid-Tethered Dihydropyridines

Conjugation of amino acids to bioactive molecules has emerged as a promising strategy for optimizing pharmacological profiles of lead candidates in drug discovery. This study describes a photocatalytic Minisci-type transfer reaction of N-acyl amino acids into various N-heterocycles. Notably, this protocol enables direct conjugation of amino acids into heterocyclic C-H bonds, eliminating the need for prefunctionalized substrates. A diverse array of N-heterocycles, amino acids, oligopeptides, and drugs were used to demonstrate the potential of the proposed approach. In addition, the importance of this approach is demonstrated through its application in the DNA-encoded library chemistry. Various synthetic transformations and preliminary mechanistic investigations were also explored.