Smedley Christopher J, Barrow Andrew S, Spiteri Christian, Giel Marie-Claire, Sharma Pallavi, Moses John E
Department of Chemistry and Physics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia.
Chemistry. 2017 Jul 26;23(42):9990-9995. doi: 10.1002/chem.201701552.
Amide bond formation is one of the most executed reactions in chemistry and biology. This is largely due to the ubiquity of the amide functional group in biological molecules, natural products and pharmaceutically important drugs. We report here the development of "SuFExAmide": a new sulfur-fluoride exchange (SuFEx) click chemistry based protocol for the efficient amidation of carboxylic acids via acyl fluoride intermediates. We have developed benzene-1,3-disulfonyl fluoride as a cost effective, powerful and versatile coupling agent, which delivers challenging secondary and tertiary amides in excellent yields from sterically hindered and electron-deficient amines. The straightforward method offers significant benefits over existing protocols in terms of substrate scope, efficiency and ease of operation and is demonstrated by the synthesis of 44 amides, including GNF6702, an antiprotozoal drug candidate. In the majority of cases, the amide products are obtained in high yield without the need for excess reagents or chromatographic purification.
酰胺键形成是化学和生物学中执行最多的反应之一。这主要归因于酰胺官能团在生物分子、天然产物和重要药物中的普遍存在。我们在此报告“SuFExAmide”的开发：一种基于新型硫氟交换（SuFEx）点击化学的方法，用于通过酰氟中间体高效酰胺化羧酸。我们开发了苯 - 1,3 - 二磺酰氟作为一种经济高效、功能强大且通用的偶联剂，它能从空间位阻大且缺电子的胺中以优异的产率得到具有挑战性的仲酰胺和叔酰胺。这种直接的方法在底物范围、效率和操作简便性方面比现有方法具有显著优势，通过合成44种酰胺得到了证明，其中包括抗寄生虫候选药物GNF6702。在大多数情况下，无需过量试剂或色谱纯化即可高产率地获得酰胺产物。
