Faculty of Science and Engineering, Chuo University, 1-13-27 Kasuga Bunkyo-ku, Tokyo, 112-8551, Japan.
Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, 980-8578, Japan.
Angew Chem Int Ed Engl. 2023 Apr 24;62(18):e202219156. doi: 10.1002/anie.202219156. Epub 2023 Mar 22.
Synthetic methods for unsymmetrical disulfides are greatly needed owing to their applications in drug discovery, linker chemistry, and materials sciences. In this study, a new shelf-stable and easy-to-prepare bilateral disulfurating platform molecule, N-(morpholine-4-dithio)phthalimide, has been developed for the divergent synthesis of unsymmetrical disulfides. The amino and imide leaving groups of this reagent can be orthogonally transformed. Under acidic conditions, the amino moiety undergoes selective protonation and thus can be displaced by various carbon nucleophiles, such as allyl trimethylsilanes, alkynyl silanes, and electron-rich arenes, leaving the phthalimide moiety untouched. Meanwhile, the phthalimide leaving group is amenable to substitution under basic or neutral conditions. The combination of these transformations provides rapid access to diverse unsymmetrical disulfides through two C-S bond-forming reactions.
由于不对称二硫键在药物发现、连接化学和材料科学中的应用，因此非常需要不对称二硫键的合成方法。在这项研究中，开发了一种新的稳定货架期且易于制备的双边二硫化平台分子 N-(吗啉-4-二硫代)邻苯二甲酰亚胺，用于不对称二硫键的发散合成。该试剂的氨基和酰亚胺离去基团可以正交转化。在酸性条件下，氨基部分经历选择性质子化，因此可以被各种碳亲核试剂取代，如烯丙基三甲基硅烷、炔基硅烷和富电子芳基，而邻苯二甲酰亚胺部分保持不变。同时，邻苯二甲酰亚胺离去基团在碱性或中性条件下可进行取代。这些转化的结合通过两个 C-S 键形成反应提供了快速获得各种不对称二硫键的途径。
