Nature offers a variety of structurally unique, sulfated endobiotics including sulfated glycosaminoglycans, sulfated tyrosine peptides, sulfated steroids/bile acids/catecholamines. Sulfated molecules display a large number of biological activities including antithrombotic, antimicrobial, anticancer, anti‐inflammatory, and others, which arise from modulation of intracellular signaling and enhanced in vivo retention of certain hormones. These characteristics position sulfated molecules very favorably as drug‐like agents. However, few have reached the clinic. Major hurdles exist in realizing sulfated molecules as drugs. This state‐of‐the‐art has been transformed through recent works on the development of sulfate masking technologies for both alkyl (sulfated carbohydrates, sulfated steroids) and aryl (sTyr‐bearing peptides/proteins, sulfated flavonoids) sulfates. This review compiles the literature on different strategies implemented for different types of sulfate groups. Starting from early efforts in protection of sulfate groups to the design of newer SuFEx, trichloroethyl, and gem‐dimethyl‐based protection technologies, this review presents the evolution and application of concepts in realizing highly diverse, sulfated molecules as candidate drugs and/or prodrugs. Overall, the newer strategies for sulfate masking and demasking are likely to greatly enhance the design and development of sulfated molecules as non‐toxic drugs of the future.

中文翻译：

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掩蔽有机硫酸酯的合成和反应性


大自然提供了多种结构独特的硫酸化内生素，包括硫酸化糖胺聚糖、硫酸化酪氨酸肽、硫酸化类固醇/胆汁酸/儿茶酚胺。硫酸化分子表现出大量的生物活性，包括抗血栓、抗菌、抗癌、抗炎等，这些活性是通过调节细胞内信号传导和增强某些激素的体内保留而产生的。这些特性使硫酸化分子非常有利于作为类药物制剂。然而，很少有人到达诊所。实现硫酸化分子作为药物存在主要障碍。通过最近开发烷基（硫酸化碳水化合物、硫酸化类固醇）和芳基（sTyr 承载肽/蛋白质、硫酸化类黄酮）硫酸盐的硫酸盐掩蔽技术，这种最先进的技术已经发生了转变。本综述汇编了针对不同类型的硫酸盐基团实施的不同策略的文献。从早期保护硫酸基的努力开始，到设计更新的 SuFEx、三氯乙基和基于偕二甲基的保护技术，本综述介绍了在实现高度多样化的硫酸化分子作为候选药物和/或前药方面概念的演变和应用。总体而言，硫酸盐掩蔽和去掩蔽的新策略可能会极大地增强硫酸化分子作为未来无毒药物的设计和开发。