10371-86-5Relevant articles and documents
Ellipticines and 9-acridinylamines as inhibitors of d-alanine:d-alanine ligase
Vehar, Bla?,Hrast, Martina,Kova?, Andreja,Konc, Janez,Mariner, Katherine,Chopra, Ian,O'Neill, Alex,Jane?i?, Du?anka,Gobec, Stanislav
, p. 5137 - 5146 (2011)
d-Alanine:d-alanine ligase (Ddl), an intracellular bacterial enzyme essential for cell wall biosynthesis, is an attractive target for development of novel antimicrobial drugs. This study focused on an extensive evaluation of two families of Ddl inhibitors encountered in our previous research. New members of both families were obtained through similarity search and synthesis. Ellipticines and 9-acridinylamines were both found to possess inhibitory activity against Ddl from Escherichia coli and antimicrobial activity against E. coli and Staphylococcus aureus. Ellipticines with a quaternary methylpyridinium moiety were the most potent among all studied compounds, with MIC values as low as 2 mg/L in strains with intact efflux mechanisms. Antimicrobial activity of the studied compounds was connected to membrane damage, making their development as antibacterial drug candidates unlikely unless analogues devoid of this nonspecific effect can be discovered.
Synthesis and evaluation of 9-hydroxy-5-methyl-(and 5,6-dimethyl)-6H- pyrido[4,3-b]carbazole-1-N-[(dialkylamino)alkyl]carboxamides, a new promising series of antitumor olivacine derivatives
Jasztold-Howorko,Landras,Pierre,Atassi,Guilbaud,Kraus- Berthier,Leonce,Rolland,Prost,Bisagni
, p. 2445 - 2452 (1994)
Starting from 2-(2-aminoethyl)-6-methoxy-1-methylcarbazole, ethyl 9- methoxy-5-methyl-6H-pyrido[4,3-b]carbazole-1-carboxylate was obtained through a three-step sequence. This compound and its 6-methyl derivative react with (dialkylamino)alkylamines to provide various 9-methoxy-5-methyl-6H- pyrido[4,3-b]carbazole-1-(N-substituted carboxamides) whose boron tribromide demethylation afforded corresponding 9-hydroxy-1-(N-substituted carbamoyl)- olivacines. The same pathway but starting from 2-(2-aminoethyl)-6-methoxy- 1,4-dimethylcarbazole led to ethyl 9-methoxy-5,11-dimethyl-6H-pyrido[4,3- b]carbazole-1-carboxylate which did not normally react with amines. It provided either the recovered starting material at 120 °C or 9- methoxyellipticine resulting from an unexpected decarboethylation in a steel vessel at 180 °C. Biological testing of the newly obtained 1- carbamoylolivacine derivatives showed that 9-hydroxylated compounds displayed high cytotoxicity for cultured L1210 and colon 38 cells (IC50 range 5-10 nM) and good antitumor activity in vivo in the P388 leukemia and colon 38 models when administered by the iv route. The most active compound in these series is 9-hydroxy-5,6-dimethyl-1-[N-[2-(dimethylamino)ethyl]carbamoyl]-6H- pyrido[4,3-b]carbazole which was selected for further evaluation on murine solid tumors and for toxicological studies.
Simple method for preparing ellipticine or substituted ellipticine
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, (2020/05/14)
The invention relates to a synthesis process for preparing ellipticine. Ellipticine is obtained through six steps of reaction and three steps of crystallization separation, the target product total yield is high, column chromatography separation is not needed for an intermediate product and the target product, and the method is particularly suitable for large-scale preparation.
Concise Total Syntheses of Pyrido[4,3-b]carbazole Alkaloids Using Copper-Mediated 6π-Electrocyclization
Itoh, Tomoki,Abe, Takumi,Choshi, Tominari,Nishiyama, Takashi,Yanada, Reiko,Ishikura, Minoru
, p. 2290 - 2299 (2016/05/19)
Concise syntheses of 9-methoxyellipticine, 3,4-dihydroellipticine (μ-alkaloid D), 1,2,3,4-tetrahydroellipticine, 2-methyl-1,2,3,4-tetrahydroellipticine, olivacine, 3,4-dihydroolivacine, (±)-guatambuine, and (±)-janetine were developed starting from hexatriene intermediates readily obtained by Pd-catalyzed tandem cyclization/cross-coupling reaction of indolylborates. The route enables the facile construction of pyrido[4,3-b]carbazoles by Cu-catalyzed 6π-electrocyclization and subsequent transformation of the pyridocarbazole intermediates into pyrido[4,3-b]carbazole alkaloids. Concise total syntheses of pyrido[4,3-b]carbazole alkaloids were accomplished using Cu-catalyzed 6π-electrocyclization of hexatriene as a key step.
Friedel-crafts cyclodehydration approach toward the synthesis of ellipti-cine and 9-methoxyellipticine
Ramkumar, Nagarajan,Raghavendra, Medishetty S.,Nagarajan, Rajagopal
, p. 2791 - 2793 (2015/01/09)
An expedient synthesis of biologically important pyrido[4,3-b]carbazole alkaloids, ellipticine and 9-methoxyellipticine, is reported. Our synthetic approach applies a key H3PO4-mediated Friedel-Crafts cyclodehydration to construct the pyridine core.
An efficient modification of ellipticine synthesis and preparation of 13-hydroxyellipticine
Dra?ínsky, Martin,Sejbal, Jan,Rygerová, Barbora,Stiborová, Marie
, p. 6893 - 6895 (2008/02/12)
A simple modification of a previously published ellipticine synthesis is reported, which decreases the reaction time and increases the yield and purity of the product. Benzylic oxidations of 1,4-dimethylcarbazole and ellipticine derivatives were studied and 13-hydroxyellipticine was prepared.
Preparation of polyfunctional aryl azides from aryl triazenes. A new synthesis of ellipticine, 9-methoxyellipticine, isoellipticine, and 7-carbethoxyisoellipticine
Liu, Ching-Yuan,Knochel, Paul
, p. 7106 - 7115 (2008/02/11)
(Chemical Equation Presented) The preparation of polyfunctional aryl azides by the reaction of aryl triazenes with NaN3 in the presence of KHSO4 or BF3·OEt2/TFA (trifluoroacetic acid) has been described. A variety of functional groups (halides, esters, ketones, nitriles, aldehydes, and boronic esters) are tolerated under the Lewis acidic conditions. By using this methodology, the potent antitumor agents, ellipticine and 9-methoxyellipticine, have been synthesized. In addition, isoellipticine and a related derivative, 7-carbethoxyisoellipticine, were also prepared.
A Versatile and Efficient Construction of the 6H-Pyridocarbazole Ring System. Syntheses of the Antitumor Alkaloids Ellipticine, 9-Methoxyellipticine, and Olivacine and Their Analogues
Gribble, Gordon W.,Saulnier, Mark G.,Obaza-Nutaitis, Judy A.,Ketcha, Daniel M.
, p. 5891 - 5899 (2007/10/02)
A general and efficient synthesis of the 6H-pyridocarbazole ring system is described, in which the key steps are (1) regioselective acylation of a 2-lithio-1-(phenylsulfonyl)indole (14) with 3,4-pyridinedicarboxylic acid anhydride (10), (2) cyclization of the deprotected keto acid 17 to keto lactam 19 with acetic anhydride, and (3) the addition of methyllithium to give, after reduction of the intermediate diol 23 with sodium borohydride, the target ring system.In this fashion, ellipticine (1a), 9-methoxyellipticine (1b), and 9-hydroxyellipticine (1c) were synthesized in excellent overall yields from indole.The use of Superhydride, in place of 1 equiv of methyllithium, provided a synthesis of olivacine (2), and the use of phthalic anhydride in the sequence allowed for the preparation of 6,11-dimethylbenzocarbazole (48).The overall yields of ellipticine (1a) (54percent) and 9-methoxyellipticine (1b) (47percent) in six steps from their respective indoles represent one of the most efficient syntheses of these antitumor alkaloids.
Chemistry of 6H-pyridocarbazoles. Part 9. An Efficient Route to 3-indoles and the Synthesis of Some New Ellipticines
Sainsbury, Malcolm,Weerasinghe, Deepthi,Dolman, David
, p. 587 - 590 (2007/10/02)
A new and efficient route to 3-indoles has been developed which requires the Fisher indolisation of 3-(3-pyridyl)butanal with arylhydrazines.The ethylpyridylindoles can be converted into 6H-pyridocarbazoles by a known procedure, leading to the first synthesis of 7-chloro-, 7-fluoro-, 7-methyl-, 8-methoxy-, and 8-hydroxy-ellipticines.The last-named compound is identical with a minor metabolite of ellipticine in Aspergillus alliaceus.
