Saito Masato, Kobayashi Yusuke, Takemoto Yoshiji
Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Shimoadachi-cho, Yoshida, Sakyo-ku, Kyoto, 606-8501, Japan.
Chemistry. 2019 Aug 6;25(44):10314-10318. doi: 10.1002/chem.201902699. Epub 2019 Jul 10.
The reactions of thioamides with ortho-nitro-substituted iodonium ylides proceeded under mild conditions to give enaminones or thiazoles, depending on the iodonium ylide used. This protocol allowed the use of protic solvents, including aqueous solutions, and therefore coupling reactions with complex molecules such as peptides or steroids were possible. A mild and efficient method for the synthesis of various iodonium ylides was established. DFT calculations suggested that the halogen bonding between a thioamide and iodonium ylide was important in this chemoselective coupling reaction. The potential use of enaminones conjugated with pharmaceuticals as prodrugs was also demonstrated.
硫代酰胺与邻硝基取代的碘叶立德的反应在温和条件下进行,根据所用的碘叶立德不同,可生成烯胺酮或噻唑。该方法允许使用质子性溶剂,包括水溶液,因此与肽或类固醇等复杂分子的偶联反应成为可能。建立了一种温和有效的合成各种碘叶立德的方法。密度泛函理论计算表明,硫代酰胺与碘叶立德之间的卤键在这种化学选择性偶联反应中很重要。还证明了与药物共轭的烯胺酮作为前药的潜在用途。