[Syntheses designed to produce 8-amino ellipticine. Synthesis and pharmacological properties of 8-nitro ellipticine].

Abstract

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.

• Authors: C Gansser, X Lévque, M Plat, C Viel
• Journal: Il Farmaco; edizione scientifica (Farmaco Sci) Vol. 37 Issue 5 Pg. 283-97 (May 1982) ISSN: 0430-0920 [Print] Italy
• Vernacular Title: Synthèses en vue de l'obtention de l'amino-8 ellipticine: synthèse et propriétés pharmacologiques de la nitro-8 ellipticine.
• PMID: 7095141 (Publication Type: English Abstract, Journal Article)

Chemical References

• Alkaloids
• Antineoplastic Agents
• Ellipticines
• 8-nitroellipticine
• DNA

Topics

• Alkaloids (chemical synthesis)
• Animals
• Antineoplastic Agents (chemical synthesis)
• Chemical Phenomena
• Chemistry
• DNA (metabolism)
• Ellipticines (chemical synthesis, pharmacology)
• Leukemia L1210 (drug therapy)
• Mice
• Mice, Inbred DBA