Xi Gao-Lei, Liu Zai-Qun
Department of Organic Chemistry, College of Chemistry, Jilin University, Changchun 130021, China.
Department of Organic Chemistry, College of Chemistry, Jilin University, Changchun 130021, China.
Eur J Med Chem. 2015 May 5;95:416-23. doi: 10.1016/j.ejmech.2015.03.061. Epub 2015 Mar 28.
Fifteen 8-substituted-phenyl-6-ferrocenyl-4-methyl-2H-pyrano[3,2-g]quinolin-2-ones were synthesized via Povarov three-component reaction, in which the substituted aromatic aldehydes reacted with ferrocenylacetylene and 7-amino-4-methylcoumarin in the presence of Ce(OTf)3 as the catalyst. The obtained coumarin-fused quinolines were applied to quench 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS(+)) and 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH) and to inhibit 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH)-induced oxidation of DNA. It was found that the ferrocenyl group attaching to pyrano[3,2-g]quinolin-2-one scaffold can trap radicals and inhibit DNA oxidation even in the absence of phenolic hydroxyl group. The inhibitory effects on radicals and DNA oxidation can be further enhanced by the electron-donating groups such as p-(N,N-dimethyl amino)phenyl, ferrocenyl, and furan-2-yl group at 8-position. Therefore, ferrocenyl-substituted pyrano[3,2-g]quinolin-2-one skeleton together with electron-donating groups became a novel structural style for antioxidants.
通过Povarov三组分反应合成了15种8-取代苯基-6-二茂铁基-4-甲基-2H-吡喃并[3,2-g]喹啉-2-酮，其中取代的芳香醛在三氟甲磺酸铈作为催化剂的存在下与二茂铁乙炔和7-氨基-4-甲基香豆素反应。所得到的香豆素稠合喹啉用于猝灭2,2'-偶氮二(3-乙基苯并噻唑啉-6-磺酸盐)阳离子自由基(ABTS(+))和2,2'-二苯基-1-苦基肼自由基(DPPH)，并抑制2,2'-偶氮二(2-脒基丙烷盐酸盐)(AAPH)诱导的DNA氧化。发现连接到吡喃并[3,2-g]喹啉-2-酮骨架上的二茂铁基团即使在没有酚羟基的情况下也能捕获自由基并抑制DNA氧化。在8位上的给电子基团如对-(N,N-二甲基氨基)苯基、二茂铁基和呋喃-2-基可进一步增强对自由基和DNA氧化的抑制作用。因此，二茂铁基取代的吡喃并[3,2-g]喹啉-2-酮骨架与给电子基团一起成为一种新型的抗氧化剂结构类型。
