Direct Molecular Editing of Complex Molecules for Drug Discovery

ABSTRACT Innovative synthetic methods that allow for the direct, efficient modification of complex lead compounds are essential for accelerating drug development. In particular, molecular editing enables the precise, late‐stage diversification of privileged scaffolds, streamlining the drug optimization process. This review systematically evaluates the rapidly expanding repertoire of molecular editing, predominantly focusing on editing natural products and drug molecules. We classify these strategies into skeletal and peripheral editing, assembling recent representative cases that illustrate their utility in direct editing of complex molecules. Complementing these chemical approaches, biomimetic molecular editing (also called nature‐inspired molecular editing) is briefly discussed. By highlighting strategies that enable the site‐selective diversification of complex scaffolds, this review seeks to guide future efforts in the direct late‐stage editing of natural products and drug molecules.