A new environmentally friendly approach for the synthesis of idrocilamide (1), a marketed myorelaxant and anti-inflammatory agent, is reported herein. The synthetic strategy involves a solvent-free aminolysis reaction catalyzed by zinc-containing species (ZnCl2 , montmorillonite K10 (MK10) impregnated with ZnCl2 or eco-catalysts). The latter have been prepared from the aerial parts of Lolium perenne L. plants grown on contaminated soils from northern France without and with thermal activation at 120 °C and supported on MK10 (Ecocat1 and Ecocat2, respectively). The best aminolysis catalysts in the current study (ZnCl2 and Ecocat2) were selected for additional aminolyses. Compared to ZnCl2 , Ecocat2 had the advantage of being reusable over five test runs and constituted a sustainable catalyst allowing a green route to idrocilamide. Synthesized derivatives 1-4, 6 and 9 were first evaluated for their effect on reactive oxygen species (ROS) generation from macrophages and displayed antioxidant properties by preventing ROS production. Next, the analysis of the effect of molecules 1-4, 6 and 9 on macrophage migration between epithelial cells to human opportunistic fungus Candida albicans indicated that molecules 2-4, 6 and 9 exert anti-inflammatory properties via reducing macrophage migration while the parent idrocilamide (1) did not show any significant effect. This work opens the way for the discovery of new analogues of idrocilamide with improved properties.

中文翻译：

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用于合成具有抗氧化和抗炎性能的酰胺的新型高效生态友好型负载型催化剂。

本文报道了一种新的环保方法，用于合成碘甲酰胺（1），一种市售的松懈剂和抗炎剂。合成策略涉及由含锌物质（ZnCl2，浸渍有ZnCl2的蒙脱土K10（MK10）或生态催化剂）催化的无溶剂氨解反应。后者是从生长在法国北部受污染土壤上的黑麦草植物的空中部分制备的，该土壤未经加热并在120°C下热活化，并在MK10（分别为Ecocat1和Ecocat2）上支撑。选择了当前研究中最好的氨解催化剂（ZnCl2和Ecocat2）用于其他氨解。与ZnCl2相比，Ecocat2具有可在五次测试中重复使用的优势，并构成了可持续的催化剂，从而允许绿色途径合成idrocilamide。首先评估合成的衍生物1-4、6和9对巨噬细胞产生的活性氧（ROS）的影响，并通过阻止ROS的产生展示其抗氧化性能。接下来，分析分子1-4、6和9对巨噬细胞在上皮细胞之间迁移至人机真菌白念珠菌的影响表明，分子2-4、6和9通过减少巨噬细胞迁移而发挥抗炎特性，而亲本idrocilamide（1）没有显示任何明显的作用。这项工作为发现具有改进特性的新的碘溴酰胺类似物开辟了道路。分子1-4、6和9对巨噬细胞在上皮细胞之间迁移至人为机会性真菌白色念珠菌的影响的分析表明，分子2-4、6和9通过减少巨噬细胞迁移而发挥抗炎特性，而亲本碘碳酰胺1）没有表现出明显的作用。这项工作为发现具有改进特性的新的碘溴酰胺类似物开辟了道路。分子1-4、6和9对巨噬细胞在上皮细胞之间迁移至人为机会性真菌白色念珠菌的影响的分析表明，分子2-4、6和9通过减少巨噬细胞迁移而发挥抗炎特性，而亲本idrocilamide（ 1）没有表现出明显的作用。这项工作为发现具有改进特性的新的碘溴酰胺类似物开辟了道路。