化学
环加成
反应性(心理学)
亲核细胞
芳基
取代基
水溶液
亚胺
生物正交化学
腈
试剂
电泳剂
药物化学
组合化学
有机化学
点击化学
烷基
催化作用
医学
替代医学
病理
作者
Ming Fang,Gangam Srikanth Kumar,Qing Lin
出处
期刊:ChemBioChem
[Wiley]
日期:2023-06-14
卷期号:24 (14)
被引量:1
标识
DOI:10.1002/cbic.202300398
摘要
We report the synthesis of a series of hydrazonyl sultones (HS) containing an ortho-CF3 group, a five- or six-membered sultone ring, and a varying N-aryl substituent, and characterization of their aqueous stability and reactivity toward bicyclo[6.1.0]non-4-yn-9-ylmethanol (BCN) in a 1,3-dipolar cycloaddition reaction. To avoid purification of highly polar intermediates, we employed two protecting groups in our synthetic schemes. Most HS were obtained in moderate to good yields under optimized reaction conditions. The X-ray crystal structure analysis of two HS revealed that the partially negative-charged fluorine atoms in CF3 electrostatically shield the electrophilic nitrile imine (NI) center from a nucleophilic attack, underpinning their extraordinary aqueous stability. In addition, the N-aryl substituents further modulate HS reactivity and stability, with the electron-rich six-membered HS displaying excellent aqueous stability and increased cycloaddition reactivity. The utility of these improved HS reagents was demonstrated through fast and selective modification of a BCNK-encoded nanobody with second-order rate constants as high as 1500 M-1 s-1 in phosphate-buffered saline-ethanol (9 : 1), representing the fastest HS-BCN ligation reported in the literature.
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