Li Yifan, Zhang Weigang, Kweon Jeonguk, Pan Yi, Wang Qing, Chang Sukbok, Wang Yi
Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, 163 Xianlin Avenue, 210023, Nanjing, China.
State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, 163 Xianlin Avenue, 210023, Nanjing, China.
Nat Commun. 2025 Jan 3;16(1):377. doi: 10.1038/s41467-024-55786-7.
Sulfur-containing units are fundamental components widely found in bioactive compounds, prompting notable efforts toward developing synthetic methodologies for incorporating sulfur functionality into organic precursors. The synthesis of sulfinate esters and sulfinamides has garnered significant interest owing to their immense potential for applications, especially in drug development. However, most existing synthetic protocols suffer from some limitations. To address these challenges, we herein present a practical and efficient approach for the reductive sulfinylation of diverse nucleophiles with sulfonylpyridinium salts (SulPy) through the nucleophilic chain substitution, namely SC reaction, which involves S(VI) to S(IV) nucleophilic chain isomerization process. These versatile sulfinylation reagents can be readily accessed from diverse commercially available resourses. The late-stage modification of complex molecules and the ability to rapidly synthesize numerous sulfinyl bioisosteres of various drugs highlights the utility of this protocol.
含硫单元是广泛存在于生物活性化合物中的基本组成部分，这促使人们为开发将硫官能团引入有机前体的合成方法付出了显著努力。亚磺酸酯和亚磺酰胺的合成因其巨大的应用潜力，尤其是在药物开发中的潜力，而引起了广泛关注。然而，大多数现有的合成方案都存在一些局限性。为应对这些挑战，我们在此提出一种实用且高效的方法，通过亲核链取代反应，即SC反应，用磺酰基吡啶盐（SulPy）对各种亲核试剂进行还原亚磺酰化反应，该反应涉及S(VI)到S(IV)的亲核链异构化过程。这些多功能的亚磺酰化试剂可以很容易地从各种市售资源中获得。复杂分子的后期修饰以及快速合成各种药物的众多亚磺酰基生物电子等排体的能力突出了该方案的实用性。
