Skeletal editing based on nitrogen-atom manipulation

Abstract

Molecular skeletal editing has become a powerful tool in modern synthetic chemistry, enabling a diverse array of unprecedented molecular transformations. Owing to the ubiquitous presence of nitrogen atoms in bioactive natural molecules and their pivotal role in synthetic building blocks, nitrogen-atom manipulation—referred to as N-atom editing—has garnered significant attention. In the past five years, substantial progress has been made in developing novel methodologies, expanding the technique's potential across various fields, particularly in medicinal chemistry and materials science. This tutorial review provides a structured and in-depth overview of N-atom editing, tracing its historical development and highlighting recent breakthroughs. Mechanistic insights are discussed in detail, providing researchers with valuable insights and conceptual tools for future investigations. Furthermore, the transformative applications of these methodologies in synthesizing and modifying bioactive molecules, natural products, pharmaceuticals, and functional materials are illustrated through representative examples. Finally, the review concludes with a discussion of the challenges and future perspectives in N-atom editing.