- Chemistry of 6H-Pyridocarbazoles. Part 10 - Carbon-13 Nuclear Magnetic Resonance Spectra of Ellipticines and some Model Compounds
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The 13C NMR spectrum of ellipticine has been re-interpreted by reference to model compounds, and correlated with the spectra of a number of new ellipticine derivatives.
- Sainsbury, M.,Watkins, D.,Weerasinghe, D. K.
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- Exploiting an intramolecular Diels-Alder cyclization/dehydro-aromatization sequence for the total syntheses of ellipticines and calothrixin B
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The tetracyclic and pentacyclic skeletons of pyrido and quinolinocarbazole alkaloids have been synthesizedviaa unified strategy. The prominent key step involved a Diels-Alder intramolecular cyclization/dehydro-aromatization sequence. From these carbazole-lactam cores, linear syntheses have been developed for ellipticines and calothrixin B.
- Deng, Chengdan,Liu, Yuancui,Xu, Mei,Xie, Kaiqiang,Liu, Sheng
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- Regioselection Switch in Nucleophilic Addition to Isoquinolinequinones: Mechanism and Origin of the Regioselectivity in the Total Synthesis of Ellipticine
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Ellipticine was synthesized in six steps and 20% global yield starting from the readily available 2,5-dimethoxy isoquinoline. Unprecedented regioselective control of the nucleophilic attack on the isoquinoline-5,8-dione is first described. Investigation of the possible pathways of this transformation through density functional theory calculations reveals unexpected N-oxide assistance in cascade tautomerizations, which was crucial for directing the nucleophilic attack and hastening the overall process. Using this strategy, we prepared the aniline-isoquinolinedione adduct and submitted it to an intramolecular double C-H cross-coupling activation to furnish ellipticinequinone, which gave ellipticine after a MeLi addition/BH3reduction sequence.
- Castro, Joaquim A. M.,Ligiéro, Carolina B. P.,Maior, Christian R. S.,Miranda, Paulo C. M. L.,Morgon, Nelson H.,Naciuk, Fabrício F.,Rocco, Silvana A.,Serikava, Bruno K.
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- Simple method for preparing ellipticine or substituted ellipticine
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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.
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- Synthesis and cytotoxicity of novel bisellipticines and bisisoellipticines
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A series of bis-ellipticines 7-9 and bis-isoellipticines 10-12 tethered through the indole nitrogen was synthesized and screened for antitumor cytotoxicity in the L-1210 murine leukemia assay. Activity was only displayed by 1,10-bis(6-ellipticinyl)-?-decane (8).
- Obaza-Nutaitis, Judy A.,Gribble, Gordon W.
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p. 171 - 187
(2019/07/31)
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- Total Synthesis of Olivacine and Ellipticine via a Lactone Ring-Opening and Aromatization Cascade
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Effective preparation of olivacine and ellipticine via late-stage D-ring cyclization is described. Key features of the synthetic routes include trifluoroacetic acid-mediated formation of a lactone that is fused to a tetrahydrocarbazole derivative and its one-pot two-step ring opening and aromatization mediated by para-toluenesulfonic acid and palladium on carbon, respectively.
- Dilek, ?mer,Patir, Süleyman,Tilki, Tahir,Ertürk, Erkan
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p. 7901 - 7916
(2019/06/17)
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- Regioexhaustive Functionalization of the Carbocyclic Core of Isoquinoline: Concise Synthesis of Oxoaporphine Core and Ellipticine
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A general and versatile strategy has been developed for the functionalization of the carbocyclic core of the isoquinoline. This regioexhaustive approach employs electrophilic halogenation as a toolbox methodology and delivers highly decorated intermediates that can be further elaborated toward medicinally relevant building blocks or natural products.
- Horváth, Dániel Vajk,Domonyi, Frigyes,Palkó, Roberta,Lomoschitz, Andrea,Soós, Tibor
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p. 2181 - 2190
(2018/03/21)
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- Synthesis and in vitro antitumor activity of 9-hydroxyellipticine derivatives with glucose conjugation via triazolylmethyl succinate linker
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Three types of novel 9-hydroxyellipticine derivatives 7a-c with glucose conjugation, linked by a triazolylmethyl succinic ester bond, were synthesized, and their cytotoxicity against HeLa S-3 and 293T cells was evaluated together with ellipticine (1) and 9-hydroxyellipticine (3). These new compounds 7a-c exhibited potent antitumor activity against HeLa S-3 and 293T, and water solubility of 7a was greatly higher than those of 1 and 3. The effects of an -OCH2CH2-spacer and the amino sugar moiety on the antitumor activity were examined using 7b,c. Furthermore, one of these glucose-conjugates 7a was applied to hydrolysis, catalyzed by carboxyesterase, leading to the formation of 3 under physiological conditions.
- Sato, Naoya,Kawai, Yu,Akaba, Yosuke,Honma, Shoji,Sakai, Norio,Konakahara, Takeo
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p. 664 - 679
(2016/05/09)
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- SMALL MOLECULES TARGETING REPEAT r(CGG) SEQUENCES
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The invention provides a series of bioactive small molecules that target expanded r(CGG) repeats, termed r(CGG)exp, that causes Fragile X-associated Tremor Ataxia Syndrome (FXTAS). The compound was identified by using information on the chemotypes and RNA motifs that interact. Specifically, 9-hydroxy-5,11-dimethyl-2-(2-(piperidin-1-yl)ethyl)-6H-pyrido[4,3-b]carbazol-2-ium, binds the 5′CG/3′GGC motifs in r(CGG)exp and disrupts a toxic r(CGG)exp-protein complex. Specifically, dimeric compounds incorporating two 9-hydroxyellipticine analog structures can even more potently bind the 5′CGG/3′GGC motifs in r(CGG)exp and disrupts a toxic r(CGG)exp-protein complex. Structure-activity relationships (SAR) studies determined that the alkylated pyridyl and phenolic side chains are important chemotypes that drive molecular recognition of r(CGG) repeats, such as r(CGG)exp. Importantly, the compound is efficacious in FXTAS model cellular systems as evidenced by its ability to improve FXTAS-associated pre-mRNA splicing defects and to reduce the size and number of r(CGG)exp-protein aggregates.
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- Friedel-crafts cyclodehydration approach toward the synthesis of ellipti-cine and 9-methoxyellipticine
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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.
- Ramkumar, Nagarajan,Raghavendra, Medishetty S.,Nagarajan, Rajagopal
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p. 2791 - 2793
(2015/01/09)
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- Synthesis and evaluation of novel ellipticines as potential anti-cancer agents
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Drugs that inhibit DNA topoisomerase I and DNA topoisomerase II have been widely used in cancer chemotherapy. We report herein the results of a focused medicinal chemistry effort around novel ellipticinium salts which target topoisomerase I and II enzymes with improved solubility. The salts were prepared by reaction of ellipticine with the required alkyl halide and evaluated for DNA intercalation, topoisomerase inhibition and growth inhibition against 12 cancer cell lines. Results from the topoisomerase I relaxation assay indicated that all novel ellipticine derivatives behaved as intercalating agents. At a concentration of 100 μM, specific topoisomerase I inhibition was not observed. Two of the derivatives under investigation were found to fully inhibit the DNA decatenation reaction at a concentration of 100 μM, indicative of topoisomerase II inhibition. N-Alkylation of ellipticine was found to enhance the observed growth inhibition across all cell lines and induce growth inhibition comparable to that of Irinotecan (CPT-11; GI50 1-18 μM) and in some cell lines better than Etoposide (VP-16; GI50 = 0.04-5.2 μM). 6-Methylellipticine was the most potent growth inhibitory compound assessed (GI50 = 0.47-0.9 μM). N-Alkylation of 6-methylellipticine was found to reduce this response with GI50 values in the range of 1.3-28 μM.
- Deane, Fiona M.,O'Sullivan, Elaine C.,Maguire, Anita R.,Gilbert, Jayne,Sakoff, Jennette A.,McCluskey, Adam,McCarthy, Florence O.
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p. 1334 - 1344
(2013/05/21)
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- A convenient access to 1,3-disubstituted furo[3,4-b]indoles by acid ion-exchange resin-catalyzed furan formation
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Efficient synthesis of furo[3,4-b]indoles starting from the corresponding indole is reported. The first route involves derivatization, protection, and deprotection steps, which stretch the syntheses. The second method provides a shorter and more efficient strategy to accessing the furoindole. The innovation starts with alkylation at C-2 of the indole presenting at the C-3 position a ketone-acetal, followed by the cycloaromatization catalyzed by polymeric ion-exchange resins. The second route represents a significant improvement over other methods previously described.
- Basset, Joan,Romero, Manel,Serra, Tha?s,Pujol, M. Dolors
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scheme or table
p. 356 - 362
(2012/01/06)
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- Ellipticines and 9-acridinylamines as inhibitors of d-alanine:d-alanine ligase
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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.
- Vehar, Bla?,Hrast, Martina,Kova?, Andreja,Konc, Janez,Mariner, Katherine,Chopra, Ian,O'Neill, Alex,Jane?i?, Du?anka,Gobec, Stanislav
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p. 5137 - 5146
(2011/10/04)
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- Modifications to the Vilsmeier-Haack formylation of 1,4-dimethylcarbazole and its application to the synthesis of ellipticines
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Figure represented. An improved method for the preparation of 3-formyl-1,4-dimethylcarbazole, a key intermediate in the synthesis of ellipticine, is presented. Conditions of the Vilsmeier-Haack reaction have been modified to facilitate the production of 3-formyl-1,4-dimethylcarbazole as a major product leading to an overall improvement in yield of ellipticine from 3% to 14%. This approach was also applied to the synthesis of 6-methylellipticine and 9-methoxyellipticine.
- Deane, Fiona M.,Miller, Charlotte M.,Maguire, Anita R.,McCarthy, Florence O.
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p. 814 - 823
(2011/10/04)
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- Efficient microwave-assisted synthesis of ellipticine through N-(1,4-dimethyl-9h-carbazol-3-ylmethyl)-n-tosylaminoacetaldehyde diethyl acetal
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The long-lasting problematic low yield in the D-ring cyclization of ellipticine (1a) was dramatically improved through N-(1,4-dimethylcarbazol-3- ylmethyl)-N-tosylaminoacetaldehyde diethyl acetal with microwave irradiation. The overall yield of 1a starting from indole was significantly increased by 25-fold. This new approach is superior to reported methods in yields and, reaction time, and it provides efficient access to a broad spectrum of ellipticine derivatives.
- Lee, Hsueh-Yun,Chen, Grace Shiahuy,Chen, Chien-Shu,Cherna, Ji-Wang
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scheme or table
p. 454 - 458
(2010/06/19)
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- An expedient synthesis of ellipticine via Suzuki-Miyaura coupling
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A simple and efficient total synthesis of ellipticine was developed via the Suzuki-Miyaura coupling of sterically sensitive 2-hydroxybenzeneboronic acid with a multifunctional aryl halide using Pd(OAc)2 as a catalyst and Cu(OAc)2·H2O as an additive in DMSO/H2O as a key step followed by double N-arylation and cyclization.
- Konakahara, Takeo,Kiran,Okuno, Yuri,Ikeda, Reiko,Sakai, Norio
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supporting information; experimental part
p. 2335 - 2338
(2010/06/13)
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- Preparation of polyfunctional aryl azides from aryl triazenes. A new synthesis of ellipticine, 9-methoxyellipticine, isoellipticine, and 7-carbethoxyisoellipticine
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(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.
- Liu, Ching-Yuan,Knochel, Paul
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p. 7106 - 7115
(2008/02/11)
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- An efficient modification of ellipticine synthesis and preparation of 13-hydroxyellipticine
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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.
- Dra?ínsky, Martin,Sejbal, Jan,Rygerová, Barbora,Stiborová, Marie
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p. 6893 - 6895
(2008/02/12)
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- Regioselective synthesis of ellipticine
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An eight-step synthesis of the tetracyclic pyridocarbazole alkaloid ellipticine (=5,11-dimethyl-6H-pyrido[4,3-b]carbazole; 1a) in an overall yield of 13% is reported, starting from 4,7-dimethyl-1H-indene. Key steps were iodination, Suzuki coupling, reductive cyclization, DDQ oxidation, and heterocyclization under loss of H2O.
- Ho, Tse-Lok,Hsieh, Sheng-Ying
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p. 111 - 116
(2007/10/03)
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- Synthesis of ellipticine: A radical cascade protocol to aryl- and heteroaryl-annulated[b]carbazoles
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Imidoyl selanides, synthesized from amides, have been used as radical precursors of imidoyl radicals in cascade reactions. The novel radical cascade has been developed for the simple synthesis of the medicinally important aryl-annulated[b]-carbazoles. The protocol has been exemplified with the high-yielding total synthesis of the anticancer alkaloid ellipticine.
- Pedersen, Jan M.,Bowman, W. Russell,Elsegood, Mark R. J.,Fletcher, Anthony J.,Lovell, Peter J.
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p. 10615 - 10618
(2007/10/03)
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- Synthesis of 3-methoxyellipticine andellipticine by friedel-crafts reaction of indole-2,3-dicarboxylic anhydride and selective demethylation
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Reaction of 1-benzylindole-2,3-dicarboxylic anhydride with 2,4,6-trimethoxypyridine in the presence of a Lewis acid gave 1-benzyl-3-(2,4,6-trimethoxynicotinoyl)indole-2-carboxylic acid as the sole product in high yield, which could be changed to 1-benzyl-3-(2,4,6-trimethynicotinoyl)indole. 1-Benzyl-3-(2,4,6-trimethoxynicotinoyl)indole was converted to 3-methoxyellipticine and ellipticine by selective demethylation and triflation of the methoxy group.
- Miki, Yasuyoshi,Aoki, Yoshiyuki,Tsuzaki, Yasuhiko,Umemoto, Misako,Hibino, Hajime
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p. 2693 - 2703
(2007/10/03)
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- Synthesis of ellipticine by reaction of 1-(4-methoxybenzyl)indole-2,3-dicarboxylic anhydride with (3-bromo-4-pyridyl)-triisopropoxytitanium
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The synthesis of ellipticine by the reaction of 1-(4-methoxybenzyl)indole-2,3-dicarboxylic anhydride with (3-bromo-4-pyridyl)-triisopropoxytitanium was reported. The reaction involved the deprotection of the 1-(4-methoxybenzyl) group of the 2-acylindole-3-carboxylic acid by treatment with perchloric acid in acetic acid to afford 2-(3-bromoisonicotinoyl)indole, which was then converted to ellipticine. The effect of different reagents and conditions on the reaction was observed and infrared spectrometry was performed on the products.
- Miki, Yasuyoshi,Hachiken, Hiroko,Yanase, Norihide
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p. 2213 - 2216
(2007/10/03)
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- Synthesis of ellipticine by hetaryne cycloadditions - Control of regioselectivity
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We have modified Gribble's and Moody's approaches to ellipticines by introducing substituents into the 3,4-didehydropyridine dienophile to control the key cycloaddition step. A chloro substituent at position 2 improved the yields and the regioselectivities of the cycloadditions and the overall efficiency of the synthesis of ellipticine.
- Díaz, Maite,Cobas, Agustín,Guitián, Enrique,Castedo, Luis
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p. 4543 - 4549
(2007/10/03)
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- An efficient total synthesis of ellipticine
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A total synthesis of ellipticine could be attained through the palladium catalyzed tandem cyclization-cross-coupling reaction of indolylborate (2b) with vinyl bromide (3) as a key reaction.
- Ishikura, Minoru,Hino, Ayako,Katagiri, Nobuya
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- A novel entry to pyrido[4,3-b]carbazoles: An efficient synthesis of ellipticine
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The palladium catalyzed tandem cyclization-cross-coupling reaction of indolylborate (2) with vinyl bromide (9) was developed for the preparation of pyrido[4,3-b]carbazole as a key reaction. The cross-coupling reaction of 2a provided hexatriene (10), and then cyclization of 10 to pyrido[4,3- b]carbazole (12) was effected with irradiation or Lewis acid. Using indolylborate (2c) for the cross-coupling reaction, a novel construction of ellipticine was attained through similar reaction sequences.
- Ishikura, Minoru,Hino, Ayako,Yaginuma, Toshikatsu,Agata, Isao,Katagiri, Nobuya
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p. 193 - 207
(2007/10/03)
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- Intramolecular cyclization of ortho-(cyclohex-2-enyl)anilines. Modified synthesis of ellipticine
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It was found that the reactions of arylamines with 3-bromocyclohexene afforded hydrocarbazole compounds in 64-78% yields. A modified procedure for the synthesis of antitumor alkaloid ellipticine was proposed.
- Mustafin,Khalilov,Ismagilov,Baimetov,Spirikhin,Abdrakhmanov,Tolstikov
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p. 2121 - 2126
(2007/10/03)
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- Polar Control of the Regioselectivity of Hetaryne Cycloadditions. Synthesis of Ellipticine
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A regioselective cycloaddition between 1,3-dimethyl-4-(phenylsulfonyl)-4H-furoindole and 2-chloro-3,4-didehydropyridine is the key step of a modification of Gribble's approach to ellipticines.The use of a fluoride-promoted elimination for the generation of the pyridine and the control of the regioselectivity of the cycloaddition improve the yield of ellipticine by a factor of 3.
- Diaz, M. Teresa,Cobas, Agustin,Guitian, Enrique,Castedo, Luis
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p. 157 - 158
(2007/10/03)
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- Reaction of indole-2,3-dicarboxylic anhydride with (3-bromo-4-pyridyl)triisopropoxytitanium: Synthesis of ellipticine
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N-Benzylindole-2,3-dicarboxylic anhydride (1) was reacted with (3-bromo-4-pyridyl)triisopropoxytitanium to give 2-(3-bromoisonicotinoyl)indole-3-carboxylic acid (2) as the sole product in high yield, which could be converted to ellipticine in six steps.
- Miki, Yasuyoshi,Tada, Yoshitaka,Yanase, Norihide,Hachiken, Hiroko,Matsushita, Ko-Ichi
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p. 7753 - 7754
(2007/10/03)
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- INTRAMOLECULAR CYCLIZATION OF ortho-(CYCLOHEX-2-ENYL)ANILINES SYNTHESIS OF ELLIPTICINE
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A convenient method is proposed for the synthesis of the alkaloid ellipticine, which possesses a pronounced antitumoral activity.The interaction of 3-bromocyclohexene (1 equiv.) and 2,5-xylylidine (4 equiv., 150 deg C, 5 h) gave a mixture of hexa- and tetrahydrocarbazoles which was dehydrogenated in the presence of Pd/C to the key synthon 1,4-dimethylcarbazole.The formylation of the carbazole by the Vilsmeier-Haack reaction, interaction with 2,2-diethoxyethylamine, and reduction of the imine formed over Raney nickel led to 3-(2,2-diethoxyethylaminomethyl)-1,4-dimethylcarbazole, the boiling of the N-tosylate of which gave ellipticine in high yield.
- Mustafin, A. G.,Khalilov, I. N.,Tal'vinskii, E. V.,Abdrakhmanov, I. B.,Spirikhin, L. V.,Tolstikov, G. A.
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p. 479 - 483
(2007/10/02)
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- A Versatile and Efficient Construction of the 6H-Pyridocarbazole Ring System. Syntheses of the Antitumor Alkaloids Ellipticine, 9-Methoxyellipticine, and Olivacine and Their Analogues
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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.
- Gribble, Gordon W.,Saulnier, Mark G.,Obaza-Nutaitis, Judy A.,Ketcha, Daniel M.
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p. 5891 - 5899
(2007/10/02)
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- Total Syntheses of Ellipticine Alkaloids and their Amino Analogues
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Staudinger reaction of 9 with triphenylphosphine gave 2,4-dihydropyrroloindole 10.Treatment of 10 with di-tert-butyl dicarbonate and 4-dimethylaminopyridine gave 11.Diels-Alder reaction of 11 with 3,4-pyridyne gave cycloadducts 12 and 13, which were converted into ellipticine 1 and isoellipticine 2.New amino analogues of ellipticine 27 and 28 were also synthesized by this new route.Key words: Ellipticine, 2,4-Dihydropyrroloindole, Staudinger Reaction
- Sha, Chin-Kang,Yang, Jeng-Fenn
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p. 10645 - 10654
(2007/10/02)
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- An Efficient Synthesis of C-11 Substituted 6H-PyridoCarbazoles
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A synthesis of the natural product 5-methyl-6H-pyridocarbazole-11-methanol, 5 from the ketolactam 7 is described.Compound 7 was treated with one equivalent of MeLi followed by quenching of the reaction mixture with water to give the lactone 19.Compound 19 was treated with a number of organolithium reagents such as methyllithium, n-butyllithium, ethoxyvinyl lithium and the lithio derivative of formaldehyde diethyl mercaptal to give, after sodium borohydride reduction, 1, 15, 30, and 31 respectively.Compounds 30 and 31 were hydrolyzed and then reduced to give compounds 5 and 6 respectively, in an overall yield of 21percent.Compounds 16 and 22 were identified as the intermediates in the Saulnier-Gribble synthesis of ellipticine. Key Words: Ellipticine; 9-Methoxy-ellipticine; PyridoCarbazole; Natural Product; Antitumor Agents
- Modi, Sandeep P.,Michael, Meged A.,Archer, Sydney,Carey, James J.
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p. 6539 - 6548
(2007/10/02)
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- Synthetic Studies of Indoles and Related Compounds, Part 221. The Vilsmeier-Haack Reaction of N-Benzyl-1,2,3,4-tetrahydrocarbazoles and its Synthetic Application to Olivacine and Ellipticine2
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Vilsmeier-Haack reaction of 9-benzyl-1,2,3,4-tetrahydrocarbazole (18a) at 120 deg C gave 9-benzyl-1-methylcarbazole-3-carbaldehyde (19a) and 9-benzyl-1-(N,N-(dimethylamino)methyl)carbazole-3-carbaldehyde (22a) in moderate yields, whereas, the same reaction at 0 deg C gave 9-benzyl-1,2,3,4-tetrahydrocarbazole-1-carbaldehyde (20a) in very good yield.The aldehyde (20a) was converted into 9-benzyl-1-methylcarbazole (21a) by another Vilsmeier-Haack reaction.This carbazole (21a) unexpectedly underwent non-regioselective formylation under similar reaction conditions to give a mixture of compound (19a) and 9-benzyl-8-methylcarbazole-3-carbaldehyde (23a).On the basis of the above results, a mechanism of the formation of the aromatic aldehyde (19a) was proposed, which involves 1,5-sigmatropic rearrangement of an N-methylidene dimethylammonium cation from the 4a-position to the 3-position as a key step.Vilsmeier-Haack reaction of 9-benzyl-1,2,3,4-tetrahydro-4-methylcarbazole (18b) at 100 deg C also gave 9-benzyl-1,4-dimethylcarbazole-3-carbaldehyde (19b) in moderate yield.The total syntheses of two antitumor alkaloids, olivacine (10) and ellipticine (11), were achieved by utilizing compounds (19a) and (19b) as key intermediates.
- Yokoyama, Yuusaku,Okuyama, Naomi,Iwadate, Shinji,Momoi, Tokuko,Murakami, Yasuoki
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p. 1319 - 1329
(2007/10/02)
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- SYNTHESIS OF 5-METHYL-6H-PYRIDOCARBAZOLE-11-METHANOL
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The structures of some of the intermediates in Saulnier-Gribble synthesis of ellipticine have been determined.One of the intermediates 8 has been converted to 5-methyl-6H-pyridocarbazole-11-methanol, an alkaloid isolated from Strychnos dinklagei.
- Modi, Sandeep P.,Carey, James J.,Archer, Sydney
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p. 5845 - 5848
(2007/10/02)
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- A REGIOSELECTIVE DIELS-ALDER SYNTHESIS OF ELLIPTICINE
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The trimethylsilyl trifluoromethanesulfonate accelerated Diels-Alder reaction between 1,3-dimethyl-4-(phenylsulfonyl)-4H-furoindole (3) and 5,6-dihydropyridones (10) shows high regioselectivity, yielding carbazole 11 upon hydrolytic workup.Carbazole 11b has been successfully converted to the pyridocarbazole alkaloid ellipticine (1).
- Davis, Deborah A.,Gribble, Gordon W.
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p. 1081 - 1084
(2007/10/02)
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- A REGIOSPECIFIC TOTAL SYNTHESIS OF ELLIPTICINE VIA NITRENE INSERTION
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Ellipticine, a 6H-pyridocarbazole alkaloid, has been regiospecifically synthesized by a general route which should allow for the preparation of a number of derivatives.The approach employs a versatile coupling reaction between phenylboronic acid and a substituted bromoisoquinoline followed by carbazole ring formation via a nitrene insertion reaction to give ellipticine.
- Miller, R. Bryan,Dugar, Sundeep
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p. 297 - 300
(2007/10/02)
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- A NEW PRECURSOR TO 3,4-DIDEHYDROPYRIDINE, AND ITS USE IN THE SYNTHESIS OF THE ANTITUMOR ALKALOID ELLIPTICINE
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A concise synthesis of the antitumor alkaloid ellipticine (1) is reported.The route involves a Diels-Alder reaction between 1,4-dimethylpyranoindol-3-one (3), easily prepared in two steps from indole, and 3,4-didehydropyridine (4), and for its successful execution required the development of a new thermal, reagent-free precursor to the aryne.This precursor, 3-(3,3-dimethyltriazen-1-yl)pyridine-4-carboxylic acid (10a), prepared from 3-aminopyridine-4-carboxylic acid, decomposes in boiling acetonitrile to generate 3,4-didehydropyridine which can be intercepted in Diels-Alder reactions with tetraphenylcyclopentadienone, furan, and 2,5-dimethylfuran.The triazenes (10b) and (10c) can be prepared and decomposed similarly.The key Diels-Alder reaction between the pyranoindolone (3) and 3,4-didehydropyridine (4) gives ellipticine (1) in 20 percent yield, together with an equal amount of isoellipticine (14).
- May, Christopher,Moody, Christopher J.
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p. 247 - 250
(2007/10/02)
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- AN EFFICIENT SYNTHESYS OF 3-ACYLCARBAZOLES AND OBSERVATIONS ON THE FURTHER ELABORATION OF THESE COMPOUNDS TO 6H-PYRIDOCARBAZOLES
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A new procedure for the synthesis of 3-acylcarbazoles useful for the construction of 6H-pyridocarbazoles is described starting from readily available gramines or indoles.This methodology is exemplified by a synthesis of the anticancer alkaloid olivacine.Some discrepancies are noted between our results and those of other authors.
- Hogan, Iain,Jenkins, Paul,Sainsbury, Malcolm
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p. 6505 - 6508
(2007/10/02)
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- FORMATION OF 3,3-DISUBSTITUTED INDOLENINES FROM INTRAMOLECULAR NITRENE REACTION WITH ISOQUINOLINE AND NAPHTHALENE MOIETIES
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Thermolysis of azides 2,7, and 14 gave nitrenes which reacted intramolecularly with isoquinoline and naphthalene moieties to produce 3,3-disubstituted indolenines 3,8, and 15, respectively, as the major products and carbazole derivatives 1,9, and 16, respectively, as the minor products.
- Miller, R. Bryan,Dugar, Sundeep,Epperson, James R.
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p. 217 - 220
(2007/10/02)
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- IMPROVED PROCEDURE FOR THE REDUCTIVE PHENYLATION AND CYCLIZATION OF NITROARENES
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The reductive phenylation of nitroarenes was improved by using iron pentacarbonyl(IPC) as a reducing reagent.The method was applied to the synthesis of ellipticine and dibenzazocine derivatives.
- Miyake, Shinji,Sasaki, Atsushi,Ohta, Toshiharu,Shudo, Koichi
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p. 5815 - 5818
(2007/10/02)
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- A Concise Synthesis of the Antitumour Alkaloid Ellipticine
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A short synthesis of the antitumour alkaloid ellipticine, based on the Diels-Alder reaction between 1,4-dimethylpyranoindol-3-one (2) and 3,4-didehydropyridine, is described.
- May, Christopher,Moody, Christopher J.
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p. 926 - 927
(2007/10/02)
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- SYNTHESIS OF ELLIPTICINE
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The 6H-pyridocarbazole system is efficiently synthesized by intramolecular attack of an ester enolate on an unactivated pyridinium salt.
- Weller, Dwight D.,Ford, Douglas W.
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p. 2105 - 2108
(2007/10/02)
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- Synthesis and Diels-Alder Reactions of 1,3-Dimethyl-4-(phenylsulfonyl)-4H-furoindole. A new Annulation Strategy for the Construction of Ellipticine and Isoellipticine
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The novel fused heterocycle 1,3-dimethyl-4-(phenylsulfonyl)-4H-furoindole (4) is synthesized from 3-ethylindole (6) in six steps (46percent yield) or from indole-3-carboxaldehyde (12) in four steps (21percent yield).Furoindole 4 undergoes Diels-Alder reactions with dimethyl acetylenedicarboxylate, N-phenylmaleimide, benzyne, and 3,4-pyridyne (5) to give the expected adducts 17, 18a,b, 19, and 23a,b, respectively.Deoxygenation and desulfonylation of 19 and 23a,b, respectively, give benzocarbazole 22 and a readily separable mixture of the pyridocarbazole alkaloids ellipticine (1a) and isoellipticine (2a).
- Gribble, Gordon W.,Saulnier, Mark G.,Sibi, Mukund P.,Obaza-Nutaitis, Judy A.
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p. 4518 - 4523
(2007/10/02)
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- An Efficient Synthesis of Ellipticine
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A synthesis of the antitumor pyridocarbazole alkaloid ellipticine (1a) is described in which the key steps are, successively, a highly regioselective acylation of 2-lithio-1-(phenylsulfonyl)indole (4) with 3,4-pyridinedicarboxylic anhydride (3) and acetic anhydride induced ring closure to give keto lactam 8.Further manipulation affords ellipticine in 54percent overall yield from indole (2a).
- Saulnier, Mark G.,Gribble, Gordon W.
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p. 2810 - 2812
(2007/10/02)
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- A NEW SYNTHESIS OF ELLIPTICINE AND OLIVACINE THROUGH PYRIDINE-3,4-QUINODIMETHANE INTERMEDIATES
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Thermolysis of 2-indole (6a) at 500 deg C for 3 min gave 11-demethylellipticine (7a).The similar reaction by using 2-indole (6b) affordedolivacine (7b).Ellipticine and 11-demethylellipticine were obtained by thermolysis of 2-indole (6c).
- Kano, Shinzo,Sugino, Eiichi,Hibino, Satoshi
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p. 1673 - 1676
(2007/10/02)
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- A GENERAL SYNTHESIS OF 6-H-PYRIDOCARBAZOLE ALKALOIDS
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A general and versatile synthesis of the 6-H-pyridocarbazole alkaloid ellipticine is described; the approach employs the coupling of an acetanilide with a bromoisoquinoline followed by heterocyclic ring formation to give ellipticine.
- Miller, R. Bryan,Moock, Thomas
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p. 3319 - 3322
(2007/10/02)
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