Department of Organic Chemistry, College of Chemistry, Jilin University, Changchun 130021, People's Republic of China.
J Org Chem. 2013 Sep 6;78(17):8696-704. doi: 10.1021/jo401426n. Epub 2013 Aug 23.
The hydroxyl-substituted benzoic acid (as phenyl group A in the product), aniline (as phenyl group B in the product), benzaldehyde (as phenyl group C in the product), and four isocyanides are employed to synthesize bis-amide via an Ugi four-component reaction. The effects of the obtained 20 bis-amides on quenching radicals and inhibiting DNA oxidation are estimated. It is found that the antioxidant effectiveness of bis-amide generated by hydroxyl groups is markedly influenced by the structural feature derived from isocyanide. The phenolic hydroxyl group attaching to phenyl group A plays a major role in scavenging radicals, and the radical-scavenging property is reinforced by the structural moiety introduced from ferrocenylmethyl isocyanide. The same conclusion is also obtained when bis-amides are used to inhibit DNA oxidation. It is still found that the ferrocenylmethyl moiety enhances the antioxidant effect of hydroxyl group at phenyl group A in protecting DNA against the oxidation. Moreover, when the bis-amide is prepared by the same isocyanide, e.g. ethyl isocyanoacetate, it is found that the hydroxyl group at phenyl group C plays the major role in inhibiting DNA oxidation, followed by the hydroxyl groups attaching to phenyl groups B and A.
羟基取代苯甲酸（作为产物中的苯基 A）、苯胺（作为产物中的苯基 B）、苯甲醛（作为产物中的苯基 C）和四种异氰化物被用于通过 Ugi 四组分反应合成双酰胺。评估了所得到的 20 种双酰胺对淬灭自由基和抑制 DNA 氧化的作用。结果发现，羟基生成的双酰胺的抗氧化效果明显受到异氰化物衍生的结构特征的影响。连接到苯基 A 的酚羟基在清除自由基中起主要作用，并且引入的二茂铁基甲基异氰化物的结构部分增强了自由基清除性能。当双酰胺用于抑制 DNA 氧化时，也得到了相同的结论。仍发现二茂铁基甲基部分增强了苯基 A 上的羟基在保护 DNA 免受氧化方面的抗氧化作用。此外，当使用相同的异氰化物（例如，乙基异氰基乙酸酯）制备双酰胺时，发现苯基 C 上的羟基在抑制 DNA 氧化中起主要作用，其次是连接到苯基 B 和 A 的羟基。
