Gansser C, Lévque X, Plat M, Viel C
Farmaco Sci. 1982 May;37(5):283-97.
The synthesis of 8-nitro ellipticine starting from 6-nitro indole is reported. It is the first derivative of ellipticine substituted in position 8 obtained by total synthesis. In contrast to 9-nitro ellipticine the 8-nitro derivative could until now not be reduced to 8-amino ellipticine. To obtain the latter it was intended to arylate an enamine of the 2,5,8-trimethyloctahydroisoquinolone-6 by 1-chloro 2,4-dinitrobenzene, followed by a reductive cyclization and N-demethylating aromatization. Since the yield of the arylation step was low, the isoquinolone was replaced by 2,5-dimethyl cyclohexanone and the synthesis would have to be completed by addition of a pyridine ring. In the case the yield of the aromatisation was 37%, but the carbazole derivative resisted all formylation attempts. 8-Nitro ellipticine was investigated for its DNA affinity, its cytotoxic activity on L 1210 tumors cells and its toxicity in the mouse. The results obtained were compared with those for 9-nitro ellipticine and in regard to cytotoxicity, with those for the 8- and 9-hydroxy ellipticines.
报道了从6-硝基吲哚出发合成8-硝基玫瑰树碱的方法。它是通过全合成得到的8位取代的玫瑰树碱的首个衍生物。与9-硝基玫瑰树碱不同，8-硝基衍生物至今仍无法还原为8-氨基玫瑰树碱。为了得到后者，打算用1-氯-2,4-二硝基苯使2,5,8-三甲基八氢异喹啉酮-6的烯胺芳基化，随后进行还原环化和N-去甲基芳构化。由于芳基化步骤的产率较低，异喹啉酮被2,5-二甲基环己酮取代，且合成必须通过添加吡啶环来完成。在这种情况下，芳构化的产率为37%，但咔唑衍生物抵抗了所有甲酰化尝试。对8-硝基玫瑰树碱的DNA亲和力、对L 1210肿瘤细胞的细胞毒性活性及其在小鼠体内的毒性进行了研究。将所得结果与9-硝基玫瑰树碱的结果进行了比较，在细胞毒性方面，与8-和9-羟基玫瑰树碱的结果进行了比较。
