[Syntheses designed to produce 8-amino ellipticine. Synthesis and pharmacological properties of 8-nitro ellipticine].
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.
D000470:Alkaloids / Q000138:chemical synthesis*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000378:metabolism; D004611:Ellipticines / Q000138:chemical synthesis* / Q000494:pharmacology; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D008811:Mice, Inbred DBA
D000470:Alkaloids; D000970:Antineoplastic Agents; D004611:Ellipticines; C035343:8-nitroellipticine; D004247:DNA
Synthèses en vue de l'obtention de l'amino-8 ellipticine: synthèse et propriétés pharmacologiques de la nitro-8 ellipticine.