Recent advances of synthetic strategies toward macrocyclic drugs

Abstract

Macrocyclic drugs, which are characterized by ring structures composed of more than 12 atoms, often exhibit enhanced druggability due to the incorporation of macrocyclic scaffolds. In recent years, these compounds have garnered increasing attention from pharmacologists, with a growing number of macrocyclic drugs receiving regulatory approval. Constructing the macrocyclic framework is inherently challenging, and the selection of an appropriate strategy for macrocycle synthesis is essential for improving the efficiency of drug development. This review examines the macrocyclic construction strategies employed in FDA-approved drugs and those in clinical development over the past decade, with the aim of attracting further interest from chemists and advancing progress in this area.