Bassini Emanuele, Gazzotti Stefano, Sannio Filomena, Presti Leonardo Lo, Sgrignani Jacopo, Docquier Jean-Denis, Grazioso Giovanni, Silvani Alessandra
Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133 Milan, Italy.
Dipartimento di Biotecnologie Mediche, Università degli Studi di Siena, Viale Bracci 16, 53100 Siena, Italy.
Antibiotics (Basel). 2020 May 12;9(5):249. doi: 10.3390/antibiotics9050249.
The application of various isonitrile-based multicomponent reactions to protected (2-oxoethyl)boronic acid (as the carbonyl component) is described. The Ugi reaction, both in the four components and in the four centers-three components versions, and the van Leusen reaction, proved effective at providing small libraries of MIDA-protected β-aminoboronic acids. The corresponding free β-aminoboronic acids, quantitatively recovered through basic mild deprotection, were found to be quite stable and were fully characterized, including by B-NMR spectroscopy. Single-crystal X-ray diffraction analysis, applied both to a MIDA-protected and a free β-aminoboronic acid derivative, provided evidence for different conformations in the solid-state. Finally, the antimicrobial activities of selected compounds were evaluated by measuring their minimal inhibitory concentration (MIC) values, and the binding mode of the most promising derivative on OXA-23 class D β-lactamase was predicted by a molecular modeling study.
本文描述了各种基于异腈的多组分反应在保护的（2-氧代乙基）硼酸（作为羰基组分）中的应用。乌吉反应，包括四组分和四中心-三组分版本，以及范鲁森反应，被证明在提供MIDA保护的β-氨基硼酸小文库方面是有效的。通过温和的碱性脱保护定量回收的相应游离β-氨基硼酸，被发现相当稳定，并进行了全面表征，包括通过硼核磁共振光谱。对一个MIDA保护的和一个游离的β-氨基硼酸衍生物进行的单晶X射线衍射分析，为固态下的不同构象提供了证据。最后，通过测量其最低抑菌浓度（MIC）值评估了所选化合物的抗菌活性，并通过分子建模研究预测了最有前景的衍生物在OXA-23 D类β-内酰胺酶上的结合模式。
