Medicinal chemistry continues to be impacted by new synthetic methods. Particularly sought after, especially at the drug discovery stage, is the ability to enact the desired chemical transformations in a concise and chemospecific fashion. To this end, the field of organic synthesis has become captivated by the idea of ‘molecular editing’—to rapidly build onto, change or prune molecules one atom at a time using transformations that are mild and selective enough to be employed at the late stages of a synthetic sequence. In this Review, the definition and categorization of a particularly promising subclass of molecular editing reactions, termed ‘single-atom skeletal editing’, are proposed. Although skeletal editing applies to both cyclic and acyclic compounds, this Review focuses on heterocycles, both for their centrality in medicinal chemistry and for the definitional clarity afforded by a focus on ring systems. A classification system is presented by highlighting methods (both historically important examples and recent advances) that achieve such transformations, with the goal to spark interest and inspire further development in this growing field.

药物化学继续受到新合成方法的影响。特别受追捧的是能够以简明和化学特异性的方式进行所需的化学转化，尤其是在药物发现阶段。为此，有机合成领域已经被“分子编辑”的想法所吸引——使用温和且选择性足以在后期阶段使用的转化，快速构建、改变或修剪分子，一次一个原子的合成序列。在这篇综述中，提出了一个特别有前途的分子编辑反应子类的定义和分类，称为“单原子骨架编辑”。尽管骨架编辑适用于环状和非环状化合物，但本综述侧重于杂环，既因为它们在药物化学中的中心地位，也因为对环系统的关注提供了明确的定义。分类系统通过强调实现此类转变的方法（历史上重要的例子和最近的进展）来呈现，目的是激发兴趣并激发这个不断发展的领域的进一步发展。