Spiropiperidines have gained in popularity in drug discovery programmes as medicinal chemists explore new areas of three-dimensional chemical space. This review focuses on the methodology used for the construction of 2-, 3- and 4-spiropiperidines, covering the literature from the last 10 years. It classifies the synthesis of each of the types of spiropiperidine by synthetic strategy: the formation of the spiro-ring on a preformed piperidine ring, and the formation of the piperidine ring on a preformed carbo- or heterocyclic ring. While 3- and 4-spiropiperidines are predominantly synthesised for drug discovery projects, 2-spiropiperidines are synthesised en route to natural products. The lack of 2-spiropiperidines in drug discovery is presumably due to limited general procedures for their synthesis.

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螺哌啶的合成策略–过去十年的回顾

当药物化学家探索三维化学空间的新领域时，螺旋哌啶已在药物发现计划中获得普及。这篇综述着重于构建2-，3-和4-螺哌啶的方法，涵盖了最近十年的文献。它通过合成策略对螺环哌啶的每种类型的合成进行了分类：在预先形成的哌啶环上形成螺环，在预先形成的碳环或杂环上形成哌啶环。而3-和4-螺哌啶主要是用于药物发现的项目合成，2-螺哌啶合成途中到天然产品。药物发现中2-螺哌啶缺乏的原因大概是由于它们合成的通用程序有限。