National Taras Shevchenko University of Kyiv, Volodymyrska Street 60 , Kyiv 01601 , Ukraine.
Institute of Bioorganic Chemistry & Petrochemistry , NAS of Ukraine , Murmanska Street 1 , Kyiv 02660 , Ukraine.
ACS Comb Sci. 2018 Nov 12;20(11):672-680. doi: 10.1021/acscombsci.8b00130. Epub 2018 Nov 1.
Multigram synthesis of (chlorosulfonyl)benzenesulfonyl fluorides is described. Selective modification of these building blocks at the sulfonyl chloride function under parallel synthesis conditions is achieved. It is shown that the reaction scope includes the use of (hetero)aromatic and electron-poor aliphatic amines (e.g., amino nitriles). Utility of the method is demonstrated by preparation of the sulfonyl fluoride library for potential use as covalent fragments, which is demonstrated by a combination of in silico and in vitro screening against trypsin as a model enzyme. As a result, several inhibitors were identified with activity on par with that of the known inhibitor.
多克合成（氯磺酰基）苯磺酰氟的方法得到了描述。在平行合成条件下，这些构建块的磺酰氯功能可以进行选择性修饰。结果表明，该反应范围包括使用（杂）芳族和缺电子脂肪族胺（例如，氨基腈）。该方法的实用性通过为潜在用作共价片段的磺酰氟文库的制备得到了证明，该文库通过计算机筛选和体外筛选胰蛋白酶作为模型酶得到了证明。结果，鉴定了几种具有与已知抑制剂相当活性的抑制剂。
