PCFM Lab and GDHPRC Lab, School of Chemistry, Sun Yat-sen University, Guangzhou, 510275, P. R. China.
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, P. R. China.
Angew Chem Int Ed Engl. 2021 Mar 22;60(13):7397-7404. doi: 10.1002/anie.202013976. Epub 2021 Feb 8.
A broad-spectrum, catalytic method has been developed for the synthesis of sulfonamides and sulfamates. With the activation by the combination of a catalytic amount of 1-hydroxybenzotriazole (HOBt) and silicon additives, amidations of sulfonyl fluorides and fluorosulfates proceeded smoothly and excellent yields were generally obtained (87-99 %). Noticeably, this protocol is particularly efficient for sterically hindered substrates. Catalyst loading is generally low and only 0.02 mol % of catalyst is required for the multidecagram-scale synthesis of an amantadine derivative. In addition, the potential of this method in medicinal chemistry has been demonstrated by the synthesis of the marketed drug Fedratinib via a key intermediate sulfonyl fluoride 13. Since a large number of amines are commercially available, this route provides a facile entry to access Fedratinib analogues for biological screening.
已开发出一种广谱的催化方法来合成磺胺类和磺胺酯。通过使用催化量的 1-羟基苯并三唑（HOBt）和硅添加剂的组合进行激活，磺酰氟化物和氟硫酸酯的酰胺化反应顺利进行，通常可以获得优异的收率（87-99%）。值得注意的是，该方案对于空间位阻较大的底物特别有效。催化剂的负载量通常较低，对于金刚烷衍生物的多克规模合成，只需使用 0.02 mol%的催化剂即可。此外，通过关键的磺酰氟中间体 13 合成市售药物 Fedratinib，证明了该方法在药物化学中的潜力。由于大量的胺是商业可得的，因此该路线为进行生物筛选提供了制备 Fedratinib 类似物的简便方法。
