Abstract In this article, we have established a highly promising approach for the synthesis of biscoumarins via domino Knoevenagel–Michael condensation of 4-hydroxycoumarin and aromatic aldehydes in 2:1 ratio using carbon-SO3H as a solid acid catalyst in H2O: EtOH (1:1). This new protocol produced α,ά-benzylidene bis(4-hydroxycoumarin) derivatives in high to excellent yields. For this, carbon-SO3H solid acid catalyst has been prepared from glycerol and sulfuric acid and characterized by FT-IR, SEM, TGA, and X-ray diffraction methods. This approach has several advantages such as high atom-economy (96.05%), excellent yields (88-100%), no need of further purification techniques, that is, column chromatography, easy workup, less reaction time, cost-effective, avoid the use of hazardous solvents, recyclability of catalyst, etc. Moreover, molecular docking studies have been performed on selected proteins methylenetetrahydrohyrofolate reductase (MTHFR) and cytochrome P450 3A4 (CYP3A4) to identify the potency of the synthesized compounds (3a–j). Among the synthesized compounds 3i, 3e, and 3b showed the highest docking score against both the proteins. Graphical Abstract

中文翻译：

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Carbon-SO3H：一种在环境反应条件下合成双香豆素的有效催化剂及其计算机研究

摘要 在本文中，我们建立了一种非常有前景的合成双香豆素的方法，通过 4-羟基香豆素和芳香醛以 2:1 的比例进行多米诺 Knoevenagel-Michael 缩合，使用碳-SO3H 作为固体酸催化剂在 H2O: EtOH (1 :1)。这种新方案以高到极好的收率生产了 α,ά-亚苄基双（4-羟基香豆素）衍生物。为此，以甘油和硫酸为原料制备了碳-SO3H 固体酸催化剂，并通过 FT-IR、SEM、TGA 和 X 射线衍射方法对其进行了表征。该方法具有原子经济性高（96.05%）、收率高（88-100%）、无需进一步纯化技术，即柱层析、易于后处理、反应时间短、成本效益高、避免有害溶剂的使用、催化剂的可回收性等。此外，已经对选定的蛋白质亚甲基四氢羟叶酸还原酶 (MTHFR) 和细胞色素 P450 3A4 (CYP3A4) 进行了分子对接研究，以鉴定合成化合物 (3a-j) 的效力。在合成的化合物 3i、3e 和 3b 中，对这两种蛋白质的对接得分最高。图形概要