Solid-Phase Synthesis of Diverse Macrocycles By Regiospecific 2-Pyridone Formation: Scope and Applications

This study introduces a novel solid-phase macrocyclization method generating 2-pyridone rings. This method relies on the intramolecular condensation between secondary and tertiary dimethoxy-propionic amide (DMPA) units. This selective reaction leads to the formation of a single, well-defined regioisomer. The method demonstrates remarkable efficiency in producing diverse peptidic and non-peptidic bioactive targets, paving the way for the development of innovative macrocycle libraries featuring the 2-pyridone unit.