SO2F2 mediated click chemistry enables modular disulfide formation in diverse reaction media

oleh: Hengzhao Li, Mengqi Peng, Junyu Li, Lijun Wang, Hainam Do, Ke Ni, Minlong Wang, Zhankui Yuan, Tianxiao Zhao, Xiaohe Zhang, Xiaoxu Zhang, Zhaonong Hu, Fazheng Ren, Jie An

Format: Article
Diterbitkan: Nature Portfolio 2024-09-01

Deskripsi

Abstract The dynamic disulfide linkage plays a vital role in various biological processes as well as drugs and biomaterials. The conversion of thiols to their corresponding disulfides is a hallmark of sulfur chemistry, but notoriously difficult to control. Achieving optimal reactivity and selectivity continues to pose significant challenges. Here, we describe a click chemistry for disulfide formation from thiols in both batch and flow-mode using SO2F2, which display exceptional selectivity toward disulfide formation through an effective nucleophilic substitution cascade. This reaction’s unique characteristics satisfy the stringent click-criteria with its high thermodynamic driving force, straightforward conditions, wide scope, quantitative yields, exceptional chemoselectivity, and non-chromatographic purification process. The modular synthesis of symmetrical, unsymmetrical, cyclic and polydisulfides is demonstrated, along with the formation of disulfide cross-linked hydrogels.