The term “click chemistry” was firstly coined by K. B. Sharpless in 2001 to refer to reactions that are high yielding, wide in scope, produce only easily removable byproducts and are stereospecific and simple to perform. Since then, this concept has been further developed and a large number of chemical reactions that fulfil totally or partially these criteria have been identified, contributing to widen the structural diversity in drug discovery campaigns, and providing chemical biologists with invaluable tools for the development of bioorthogonal reactions. In this context, several examples of the application of this concept in glycobiology and in the study of protein-protein, protein-nucleic acid and even protein-lipid interactions can be found. However, far fewer protocols have been described for the interrogation of cellular processes related to sphingolipid functions and metabolism. This review seeks to provide a concise overview of the most recent additions of click chemistry strategies to the current chemical biology toolbox, including the use of sphingolipid probes suitably functionalized for in situ click reactions, and the preparation of novel sphingolipid analogues whose design has been driven by the versatility of the archetypal [3 + 2] azide-alkyne cycloaddition.

“单击化学”一词最早由KB Sharpless于2001年提出，指的是高收率，适用范围广，仅产生易于除去的副产物且具有立体定向性且易于执行的反应。从那时起，这一概念得到了进一步发展，并且已经鉴定出完全或部分满足这些标准的大量化学反应，有助于拓宽药物发现活动中的结构多样性，并为化学生物学家提供了开发生物正交的宝贵工具。反应。在这种情况下，可以找到在糖生物学和蛋白质-蛋白质，蛋白质-核酸甚至蛋白质-脂质相互作用研究中应用该概念的几个实例。然而，已经描述了很少的用于询问与鞘脂功能和代谢有关的细胞过程的方案。这篇综述旨在提供对单击化学策略最近添加到当前化学生物学工具箱中的简要概述，包括使用经过适当功能化处理的鞘脂探针原位点击反应，以及新颖的鞘脂类似物的制备，其设计受到原型[3 + 2]叠氮化物-炔烃环加成反应的多功能性的驱动。