近日，上海有机化学研究所Jiajia Dong、美国Scripps研究所Karl Barry Sharples及湖南大学Bing Gao团队的最新研究探明了氟硫酰异氰酸酯实现醇和胺的SuFEx连接。相关论文于2021年7月14日发表在《德国应用化学》杂志上。

据介绍，氟硫酰异氰酸酯(FSI, FSO₂NCO)是独特而可靠的双亲电连接序列，用于逐步连接含醇组件到含胺基组件，因此创建了一个新的组件RO-C(=O)-NH-SO₂-NR'R"。FSI的异氰酸酯模块直接、快速地与醇和酚融合，在近乎定量产率上提供氟硫酰氨基甲酸酯。

课题组开发了一种将FSI衍生的氟硫酰氨基甲酸酯片段转化为胺的新试剂和新工艺。从第1步得到的S^VI-F组分异常稳定，考虑到不同产品的巨大结构复杂性。在与胺反应的第2步中，仅与水反应的S-N联产物产率最高。这种“在水上”的界面反应现象在这里是至关重要的，在SOF₄衍生的磺胺连接中也是如此，揭示了S^VI-F探针潜在的反应活性，在体内可能共价捕获蛋白质，这在今天的药物发现中是重要的。

SuFEx化学的范围因此大大扩大，这些磷酸盐类连接的容易进入应该被证明对于不同领域的点击化学反应都有用。

附：英文原文

Title: Fluorosulfuryl Isocyanate Enabled SuFEx Ligation of Alcohols and Amines

Author: Jiajia Dong, Karl Barry Sharpless, Bing Gao, Shoujun Sun, Junyu Chen

Issue&Volume: 2021-07-14

Abstract: Fluorosulfuryl isocyanate (FSI, FSO  2  -NCO) is established as a uniquely reliable bis-electrophilic linker for stepwise attachment of an alcohol bearing module to an amine bearing module and thence a new module RO-C(=O)-NH-SO  2  -NR’R’’ is created. The FSI’s isocyanate motif fuses directly and quickly with alcohols and phenols, affording fluorosulfuryl carbamates in nearly quantitative yield. A new reagent and process to deliver  the  FSI-derived fluorosulfuryl carbamate fragment to amines are also developed. The resulting S  VI  -F motifs from step-1 are remarkably stable, given the great structural complexities in the diverse products. In the step-2 reaction with amines, the best yield of the S-N linked products arise with water alone. This “on water” interfacial reactivity phenomenon is crucial here and also in the SOF  4  derived sulfamide ligations, revealing the latent reactivity of S  VI  -F probe for potential covalent capture of proteins in vivo which is important in today’s drug discovery. The scope of the SuFEx chemistry is largely expanded thereby and the facile entry to these phosphate-like connections should prove useful to click chemistry across diverse fields.

DOI: 10.1002/anie.202105583

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202105583