Abstract

During formylation of 2-quinolones by DMF/Et₃N mixture, the unexpected 3,3′-methylenebis(4-hydroxyquinolin-2(1H)-ones) were formed. The discussed mechanism was proved as due to the formation of 4-formyl-2-quinolone as intermediate. Reaction of the latter compound with the parent quinolone under the same reaction condition gave also the same product. The structure of the obtained products was elucidated via NMR, IR and mass spectra. X-ray structure analysis proved the anti-form of the obtained compounds, which were stabilized by the formation hydrogen bond. Molecular docking calculations showed that most of the synthesized compounds possessed good binding affinity to the SARS-CoV-2 main protease (M^pro) in comparable to Darunavir.

Graphic abstract

中文翻译：

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合成预期的抗COVID-19药物的3,3'-亚甲基双（4-羟基喹啉-2（1H）-ones）。

摘要

在DMF / Et ₃ N混合物对2-喹诺酮进行甲酰化的过程中，形成了意外的3,3'-亚甲基双（4-羟基喹啉-2（1 H）-ones）。证明了所讨论的机理是由于形成了4-甲酰基-2-喹诺酮作为中间体。后一种化合物与母体喹诺酮在相同反应条件下的反应也得到相同产物。通过NMR，IR和质谱阐明了所得产物的结构。X射线结构分析证明了所获得化合物的反形式，其通过形成氢键而稳定。分子对接计算表明，大多数合成化合物与SARS-CoV-2主蛋白酶（M ^pro）具有良好的结合亲和力，与Darunavir相当。

图形摘要