Marotta Alessandro, Kortman Hannah M, Interdonato Chiara, Seeberger Peter H, Molloy John J
Department of Biomolecular Systems, Max-Planck-Institute of Colloids and Interfaces, 14476 Potsdam, Germany.
Department of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.
Chem Commun (Camb). 2024 Nov 7;60(90):13223-13226. doi: 10.1039/d4cc04653f.
Bicyclic boronates have recently emerged as promising candidates to invoke targeted biomolecular interactions, given their selectivity for specific functionalities. Despite this, the general stability of the C-B bond , for such heterocycles, remains an intractable challenge that can often preclude their utility in drug discovery. To address this challenge, strategies that allow expedient access to strategically substituted boronates, that enable modulation of the C-B bond are urgently required. Herein we disclose an operationally simple, regioselective cross-coupling/cyclisation reaction of easily accessible boronic esters with 2-halophenols to rapidly forge 3-substituted bicyclic boronates. The utility of the platform was demonstrated expedient access to Xeruborbactam derivatives, chemoselective manipulation of formed products and the convergent approach to bicyclic boronates with a pendent biomolecular probe.
鉴于双环硼酸酯对特定官能团具有选择性，它们最近已成为引发靶向生物分子相互作用的有前景的候选物。尽管如此，对于此类杂环化合物，C-B键的一般稳定性仍然是一个棘手的挑战，这常常会妨碍它们在药物发现中的应用。为应对这一挑战，迫切需要能够方便地获得经过策略性取代的硼酸酯、能够调节C-B键的策略。在此，我们公开了一种操作简单、区域选择性的交叉偶联/环化反应，该反应利用易于获得的硼酸酯与2-卤代酚快速合成3-取代的双环硼酸酯。该平台的实用性体现在能够方便地获得西鲁巴坦衍生物、对形成的产物进行化学选择性操作以及采用带有悬垂生物分子探针的双环硼酸酯的汇聚方法。
