Journal of Organic Chemistry 2013-09-06

Ugi multicomponent reaction product: the inhibitive effect on DNA oxidation depends upon the isocyanide moiety.

Rui Wang, Zai-Qun Liu

Index: J. Org. Chem. 78(17) , 8696-704, (2013)

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Abstract

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.