Fluorosulfuryl Isocyanate Enabled SuFEx Ligation of Alcohols and Amines.
Fluorosulfuryl Isocyanate Enabled SuFEx Ligation of Alcohols and Amines.
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DOI：
10.1002/anie.202105583
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发表时间：
2021-09-20
影响因子：
16.6
通讯作者：
Dong, Jiajia
中科院分区：
文献类型：
--
作者：
Sun, Shoujun;Gao, Bing;Chen, Junyu;Sharpless, K. Barry;Dong, Jiajia
氟磺酰基异氰酸酯（FSI，FSO 2NCO）被确立为用于将带有醇的模块逐步连接到带有胺的模块的可靠的双亲电子连接剂，并且由此产生新的模块RO-C（=O）-NH-SO 2-NR ′ R ″。FSI的异氰酸酯基序直接快速地与醇和酚融合，以几乎定量的产率提供氟磺酰基氨基甲酸酯。还开发了将FSI衍生的氟磺酰基氨基甲酸酯片段递送至胺的新试剂和方法。从步骤-1得到的SVI-F基序非常稳定，因为不同产物的结构非常复杂。在与胺的步骤2反应中，S-N连接产物的最佳产率仅在水的情况下出现。这种“在水中”的界面反应性现象是至关重要的，揭示了SVI-F探针在体内潜在共价捕获蛋白质的潜在反应性，这在当今的药物发现中是重要的。SuFEx化学的范围因此大大扩展，并且这些磷酸盐类连接的简单入口应该证明对跨不同领域的点击化学有用。SuFEx在水上的连接：氟磺酰基异氰酸酯（FSI，FSO 2-NCO）是一种可靠的双亲电子连接剂，用于逐步连接醇和胺的模块。在步骤-1中，FSI的异氰酸酯与醇和酚直接快速融合，并且脂肪胺通过磺酰基氨基甲酸酯转移策略连接，两者都具有显着的选择性。在步骤-2中，S-N连接产物的最佳产率出现在独特的水上过程中。SuFEx连接的范围在药物发现和化学生物学特别感兴趣的方向上大大扩展。
Fluorosulfuryl isocyanate (FSI, FSO2NCO) is established as a 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-SO2-NR’R” is created. 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 SVI-F motifs from step-1 are remarkably stable, given the great structural complexities in 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, revealing the latent reactivity of SVI-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. SuFEx Ligation on Water: Fluorosulfuryl isocyanate (FSI, FSO2-NCO) is established as a reliable bis-electrophilic linker for stepwise attachment of alcohol and amine bearing modules. In step-1, FSI’s isocyanate fuses directly and quickly with alcohols and phenols, and aliphatic amines are attached through the sulfuryl carbamate transfer strategy, both with remarkable selectivity. In step-2, best yields of S-N linked products arise with a unique on water process. The scope of SuFEx ligation is greatly expanded in directions which would be especially interesting for drug discovery and chemical biology.
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影响因子：
4.1
作者：
Axthammer, Quirin J.;Klapoetke, Thomas M.;Krumm, Burkhard
通讯作者：
Krumm, Burkhard
影响因子：
1.8
作者：
HOFFMANN, H;FORSTER, H;TORPOGHO.G
通讯作者：
TORPOGHO.G
DOI：
10.1002/cber.19771100632
发表时间：
1977-01-01
期刊：
CHEMISCHE BERICHTE-RECUEIL
影响因子：
--
作者：
APPEL, R;MONTENARH, M
通讯作者：
MONTENARH, M
影响因子：
15
作者：
ATKINS, GM;BURGESS, EM
通讯作者：
BURGESS, EM
影响因子：
2.7
作者：
Bae, Dawon;Gautam, Jaya;Jeong, Byeong-Seon
通讯作者：
Jeong, Byeong-Seon