Department of Chemistry, University of Alberta, 4-010 Centennial Centre for Interdisciplinary Science, Edmonton, Alberta, Canada T6G 2G2.
Org Biomol Chem. 2020 May 13;18(18):3492-3500. doi: 10.1039/d0ob00572j.
This study describes the design and synthesis of arylboronic acid 2, the first example of a permanently open "frustrated" benzoxaborole, along with an exploration of its application in bioconjugation. An efficient and high yielding seven-step synthesis was optimized. NMR experiments confirmed that compound 2 exists in the open ortho-hydroxyalkyl arylboronic acid structure 2-I, a form that is effectively prevented to undergo a dehydrative cyclization as a result of unfavorable geometry. Compound 2-I conjugates effectively with amines to form stable hemiaminal ether structures, including a highly effective reaction with lysozyme. Complexation with cysteine induces an open structure containing a free hydroxymethyl arm, with the amino and thiol groups reacting preferentially with the formyl group to form a N,S-acetal.
本研究描述了芳基硼酸 2 的设计和合成，这是首例永久性开环“受阻”苯并硼氧烷，同时探索了其在生物偶联中的应用。优化了一种高效高产的七步合成方法。NMR 实验证实，化合物 2 以开环邻-羟烷基芳基硼酸结构 2-I 的形式存在，由于不利的几何形状，这种形式有效地阻止了脱水环化反应的发生。化合物 2-I 可有效地与胺缀合形成稳定的半缩醛醚结构，包括与溶菌酶的高效反应。与半胱氨酸络合诱导形成含有游离羟甲基臂的开环结构，其中氨基和巯基优先与甲酰基反应形成 N，S-缩醛。
