- Access to Indole-Fused Polyheterocycles via Pd-Catalyzed Base-Free Intramolecular Cross Dehydrogenative Coupling
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A base-free process to access indole-fused polyheterocycles via a highly efficient and atom-economic palladium-catalyzed intramolecular cross dehydrogenetive coupling (CDC) reaction of 4-aniline substituted coumarins, quinolinones, and pyrones has been developed. A wide range of indolo[3,2-c]coumarins, indolo[3,2-c]quinolinones, and indolo[3,2-c]pyrones can be facilely afforded in good to excellent yields (up to 99%).
- Cheng, Chao,Chen, Wen-Wen,Xu, Bin,Xu, Ming-Hua
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- Macrocyclic bis(ureas) as ligands for anion complexation
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Two macrocyclic bis(ureas) 1 and 2, both based on diphenylurea, have been synthesized. Compound 1 represents the smaller ring with two ethynylene groups as linkers and 2 the larger ring with two butadiynylene groups. On thermal treatment to 130 °C molecule 1 splits up into two dihydroindoloquinolinone (3) molecules. Both compounds 1 and 2 form adducts with polar molecules such as dimethyl sulfoxide (DMSO) and dimethylformamide (DMF) and act as complexing agents towards a series of anions (Cl-, Br-, I-, NO3 -, HSO4-). The crystal structures of 3, 2.2DMSO, 2.2DMF, and of the complex NEt4[Br.2] have been determined. Quantitative investigations of the complexation equilibria were performed via 1H NMR titrations. While 1 is a rather weak complexing agent, the large ring of 2 binds anions with association constants up to log K = 7.93 for chloride ions.
- Kretschmer, Claudia,Dittmann, Gertrud,Beck, Johannes
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- Copper(I)-Catalyzed Nitrile-Addition/ N-Arylation Ring-Closure Cascade: Synthesis of 5,11-Dihydro-6 H-indolo[3,2- c]quinolin-6-ones as Potent Topoisomerase-I Inhibitors
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In this paper, we present a copper(I)-catalyzed nitrile-addition/N-arylation ring-closure cascade for the synthesis of 5,11-dihydro-6H-indolo[3,2-c]quinolin-6-ones from 2-(2-bromophenyl)-N-(2-cyanophenyl)acetamides. Using CuBr and t-BuONa in dimethylformamide (DMF) as the optimal reaction conditions, the cascade reaction gave the target products, in high yields, with a good substrate scope. Application of the cascade reaction was demonstrated on the concise total syntheses of alkaloid isocryptolepine. Further optimization of the products from the cascade reaction led to 3-chloro-5,12-bis[2-(dimethylamino)ethyl]-5,12-dihydro-6H-[1,3]dioxolo[4′,5′:5,6]indolo[3,2-c]quinolin-6-one (2k), which exhibited the characteristic DNA topoisomerase-I inhibitory mechanism of action with potent in vitro anticancer activity. Compound 2k actively inhibited ARC-111- and SN-38-resistant HCT-116 cells and showed in vivo activity in mice bearing human HCT-116 and SJCRH30 xenografts. The interaction of 2k with the Top-DNA cleavable complex was revealed by docking simulations to guide the future optimization of 5,11-dihydro-6H-indolo[3,2-c]quinolin-6-ones as topoisomerase-I inhibitors.
- Hsueh, Wen-Yun,Lee, Ying-Shuan E.,Huang, Min-Sian,Lai, Chin-Hung,Gao, Yu-Sheng,Lin, Jo-Chu,Chen, Yu-Fen,Chang, Chih-Lin,Chou, Shan-Yen,Chen, Shyh-Fong,Lu, Yann-Yu,Chang, Lien-Hsiang,Lin, Shu Fu,Lin, Yu-Hsiang,Hsu, Pi-Chen,Wei, Win-Yin,Huang, Ya-Chi,Kao, Yi-Feng,Teng, Li-Wei,Liu, Hung-Huang,Chen, Ying-Chou,Yuan, Ta-Tung,Chan, Ya-Wen,Huang, Po-Hsun,Chao, Yu-Ting,Huang, Shin-Yi,Jian, Bo-Han,Huang, Hsin-Yi,Yang, Sheng-Chuan,Lo, Tzu-Hao,Huang, Guan-Ru,Wang, Shao-Yun,Lin, Her-Sheng,Chuang, Shih-Hsien,Huang, Jiann-Jyh
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- Ruthenium-and osmium-arene complexes of 2-substituted indolo[3,2- c ]quinolines: Synthesis, structure, spectroscopic properties, and antiproliferative activity
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The synthesis of new modified indolo[3,2-c]quinoline ligands L 1-L8 with metal-binding sites is reported. By coordination to ruthenium-and osmium-arene moieties 16 complexes of the type [(η6-p-cymene)M(L)Cl]Cl (1a,b-8a,b), where M is RuII or OsII and L is L1-L8, have been prepared. All compounds were comprehensively characterized by elemental analysis, electrospray ionization mass spectrometry, IR, UV-vis, and NMR spectroscopy, thermogravimetric analysis, and single-crystal X-ray diffraction (2a, 4a, 4b, 5a, 7a, and 7b). The complexes were tested for antiproliferative activity in vitro in three human cancer cell lines, namely, CH1 (ovarian carcinoma), SW480 (colon adenocarcinoma), and A549 (non-small-cell lung cancer), yielding IC 50 values in the submicromolar or low micromolar range.
- Filak, Lukas K.,Muehlgassner, Gerhard,Bacher, Felix,Roller, Alexander,Galanski, Markus,Jakupec, Michael A.,Keppler, Bernhard K.,Arion, Vladimir B.
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- Double Palladium Catalyzed Reductive Cyclizations. Synthesis of 2,2′-, 2,3′-, and 3,3′-Bi-1H-indoles, Indolo[3,2-b]indoles, and Indolo[2,3-b]indoles
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A palladium catalyzed, carbon monoxide mediated, double reductive cyclization of 1,4-, 1,3-, and 2,3-bis(2-nitroaryl)-1,3-butadienes to afford 2,2′-, 2,3′-, and 3,3′-biindoles, respectively, was developed. In contrast, reductive cyclizations of 1,2-bis(2-nitroaryl)ethenes were nonselective, affording mixtures of monocyclized indoles, indolo[3,2-b]indole, indolo[1,2-c]quinazolin-6(5H)-ones, and 5,11-dihydro-6H-indolo[3,2-c]quinolin-6-ones. Nonselective product formation was also observed from reductive cyclization of 1,1-bis(2-nitroaryl)ethenes, producing indolo[2,3-b]indoles and indolo[2,3-c]quinolin-6-ones. Carbon monoxide insertion to give the carbonyl containing products was the major or sole reaction path starting from 1,1- or 1,2-bis(2-nitroaryl)ethenes.
- Ansari, Nurul H.,Dacko, Christopher A.,Akhmedov, Novruz G.,S?derberg, Bj?rn C. G.
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p. 9337 - 9349
(2016/10/14)
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- Radical Beckmann Rearrangement and Its Application in the Formal Total Synthesis of Antimalarial Natural Product Isocryptolepine via C-H Activation
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The Beckmann rearrangement of ketoximes, mediated by ammonium persulfate-dimethyl sulfoxide as a reagent, has been achieved under neutral conditions. Based on the radical trapping and 18O-labeling experiments, the transformation follows a mechanism involving a radical pathway. The scope and generality of the developed protocol has been demonstrated by 19 examples. The developed protocol and Pd-catalyzed intramolecular double C-H activation were used as key steps in the formal total synthesis of antimalarial natural product isocryptolepine.
- Mahajan, Pankaj S.,Humne, Vivek T.,Tanpure, Subhash D.,Mhaske, Santosh B.
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supporting information
p. 3450 - 3453
(2016/07/26)
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- INDOLO[3, 2-C]QUINOLINE DERIVATIVE, METHOD FOR PRODUCING THE DERIVATIVE, AND ANTIMALARIAL AGENT AND ANTICANCER AGENT COMPRISING THE DERIVATIVE
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PROBLEM TO BE SOLVED: To provide an antimalarial agent having high antimalarial activity (especially, effective even against chloroquine-resistant malaria parasites) and high safety, and an anticancer agent having high antitumor activity and low toxicity for non-tumor cells. SOLUTION: Provided are an antimalarial agent and an anticancer agent comprising an indolo [3,2-c] quinoline derivative (A) represented by the following formula (A) or a pharmaceutically acceptable salt thereof as an active ingredient. In the formula (A), R1 represents a prescribed substituent such as a halogen atom or the like; R2 represents a prescribed substituent such as an aminoalkylamino group or the like; R3 represents an alkyl group; R4 represents a prescribed substituent such as a halogen atom or the like; n represents an integer of 1 to 4; and m represents an integer of 0 to 4. COPYRIGHT: (C)2015,JPO&INPIT
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Paragraph 0135; 0136
(2016/10/10)
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- Synthesis and in vitro cytotoxic effect of 6-amino-substituted 11H- and 11Me-indolo[3,2-c]quinolines
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A series of 6-amino-11H- indolo[3,2-c]quinoline derivatives with various substituents on the quinoline ring were synthesized. A methyl group introduced to N-11 of the intermediate 4 to elaborate novel analog 7. The cytotoxic effect of these 6-amino-substituted 11H- and 11-methyl-indolo[3,2-c]quinoline derivatives in vitro were tested against MV4-11 (human leukemia), A549 (non-small cell lung cancer) and HCT116 (colon cancer) and BALB/3T3 (normal murine fibroblasts). All the N-11 methylated compounds significantly increased the cytotoxicity. Compound 7p was most active with the IC50 value of 0.052 μM against the MV4-11 cell line, and also exhibited a selective activity against A549, HCT116 and BALB/3T3 cell line, with the respective IC50 values of 0.112, 0.007 and 0.083 μM, which were higher or comparable to those of the anticancer drug doxorubicin HCl. The binding constants of 5g and 7h to salmon fish sperm DNA were also evaluated using UV-vis absorption spectroscopy, indicating intercalation binding with constants of 1.05 × 106 L/mol and 4.84 × 106 L/mol.
- Wang, Ning,?witalska, Marta,Wu, Ming-Yu,Imai, Kento,Ngoc, Tran Anh,Pang, Cui-Qing,Wang, Li,Wietrzyk, Joanna,Inokuchi, Tsutomu
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p. 314 - 323
(2014/04/17)
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- Synthesis, β-haematin inhibition, and in vitro antimalarial testing of isocryptolepine analogues: SAR study of indolo[3,2-c]quinolines with various substituents at C2, C6, and N11
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A series of indolo[3,2-c]quinolines were synthesized by modifying the side chains of the ω-aminoalkylamines at the C6 position and introducing substituents at the C2 position, such as F, Cl, Br, Me, MeO and NO2, and a methyl group at the N11 po
- Wang, Ning,Wicht, Kathryn J.,Imai, Kento,Wang, Ming-Qi,Anh Ngoc, Tran,Kiguchi, Ryo,Kaiser, Marcel,Egan, Timothy J.,Inokuchi, Tsutomu
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p. 2629 - 2642
(2014/05/06)
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- Synthesis of diversely substituted indoloquinolinones via Pd(II)/Cu(II)-mediated oxidative C-C bond formation and I(III)-mediated C-N bond formation
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A series of indoloquinolinones bearing different aromatic substitutents were readily synthesized starting from an aryl amine, a methyl 3-oxo-3-phenylpropanoate derivative, and methoxylamine through a series of reactions of coupling/enamination, oxidative
- Zhang, Xiang,Zhang-Negrerie, Daisy,Deng, Jun,Du, Yunfei,Zhao, Kang
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p. 12750 - 12759
(2014/01/17)
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- Synthesis of phenanthridinones via palladium-catalyzed C(sp2)-H aminocarbonylation of unprotected o-arylanilines
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An efficient synthesis of free (NH)-phenanthridinones through Pd-catalyzed C(sp2)-H aminocarbonylation of unprotected o-arylanilines under an atmospheric pressure of CO has been developed. Some ortho heteroarene substituted anilines as well as
- Liang, Dongdong,Hu, Ziwei,Peng, Jiangling,Huang, Jinbo,Zhu, Qiang
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supporting information
p. 173 - 175
(2013/02/23)
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- Regioselective N-methylation of 6-chloroindolo[3,2-c]quinolines and their amination reactivity at the c-6 position
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The treatment of 6-chloroindolo[3,2-c]quinoline 6 with NaHMeI led to methylation at N-11, forming 8, while the reaction of 6 with MeI with heating gave the corresponding 5-methylated quinolinium salt whose SNAr with water smoothly proceeded to form 5-meth
- Wang, Ning,Imai, Kento,Pang, Cui-Qing,Wang, Ming-Qi,Yonezawa, Mizuho,Zhang, Yu,Nokami, Junzo,Inokuchi, Tsutomu
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p. 864 - 869
(2013/08/15)
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- Dicopper(II) and dizinc(II) complexes with nonsymmetric dinucleating ligands based on indolo[3,2-c]quinolines: Synthesis, structure, cytotoxicity, and intracellular distribution
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Dicopper(II) and dizinc(II) complexes [Cu2( MeOOCLCOO)(CH3COO)2] (1) and [Zn2(MeOOCLCOO)(CH3COO) 2] (2) were synthesized by reaction of Cu(CHsub
- Primik, Michael F.,Goeschl, Simone,Meier, Samuel M.,Eberherr, Nadine,Jakupec, Michael A.,Enyedy, Eva A.,Novitchi, Ghenadie,Arion, Vladimir B.
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supporting information
p. 10137 - 10146
(2013/09/23)
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- Quadri-synergetic effect for highly effective carbon dioxide fixation and its application to indoloquinolinone
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The first copper-catalyzed cyclic anti-nucleometallation-carboxylation of 2-alkynylanilines with carbon dioxide in the presence of dimethylzinc (ZnMe 2) and cesium fluoride (CsF) for the effective synthesis of indolyl-3-carboxylic acids and indolodihydropyran-2-one is described. Through a mechanistic study, it is unveiled that the metal ions Cu2+, Zn 2+, Cs+ and F- are working together for this CO2-based highly efficient carboxylation. Copyright
- Li, Suhua,Ma, Shengming
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p. 2387 - 2394,8
(2020/08/31)
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- A novel total synthesis of isocryptolepine based on a microwave-assisted tandem Curtius rearrangement and aza-electrocyclic reaction
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A new entry to the total synthesis of isocryptolepine (cryptosanguinolentine), isolated from Cryptolepis sanguinolenta, was achieved by constructing a tetracyclic ring system through a microwave-assisted tandem Curtius rearrangement and electrocyclic reac
- Hayashi, Kaori,Choshi, Tominari,Chikaraishi, Kyoko,Oda, Aimi,Yoshinaga, Rikako,Hatae, Noriyuki,Ishikura, Minoru,Hibino, Satoshi
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p. 4274 - 4279
(2012/07/16)
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- CuI-catalyzed photochemical or thermal reactions of 3-(2-azidobenzylidene) lactams. Application to the synthesis of fused indoles
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Photochemical or thermal reactions of 3-(2-azidobenzylidene)-lactams afforded fused indoles such as indolo[3,2-c]quinolin-6-ones, pyrido[4,3-b]indol-1-ones and other similar compounds in moderate to high yields via cyclization-ring expansion reactions. Th
- Shi, Zongjun,Ren, Yuwei,Li, Bing,Lu, Shenci,Zhang, Wei
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supporting information; experimental part
p. 3973 - 3975
(2010/07/06)
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- Structure-activity relationships of highly cytotoxic copper(II) complexes with modified indolo[3,2- c ]quinoline ligands
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A number of indolo[3,2-c]quinolines were synthesized and modified at the lactam unit to provide a peripheral binding site able to accommodate metal ions. Potentially tridentate ligands HL1a-HL4a and HL 1b-HL4b w
- Primik, Michael F.,Goeschl, Simone,Jakupec, Michael A.,Roller, Alexander,Keppler, Bernhard K.,Arion, Vladimir B.
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experimental part
p. 11084 - 11095
(2011/02/26)
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- Lewis acid catalyzed indole synthesis via intramolecular nucleophilic attack of phenyldiazoacetates to iminium ions
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(Chemical Equation Presented) Lewis acids catalyze the cyclization of methyl phenyldiazoacetates with an ortho-imino group, prepared from o-aminophenylacetic acid, to give 2,3-substituted indoles in quantitative yields.
- Zhou, Lei,Doyle, Michael P.
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supporting information; experimental part
p. 9222 - 9224
(2010/03/01)
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- Studies of the reactions between indole-2,3-diones (isatins) and 2-aminobenzylamine
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Reflux of equimolecular amounts 2-aminobenzylamine and isatins in acetic acid produced indolo[3,2-c]quinolin-6-ones in good yields. A proposed mechanism involving initial formation of a spiro compound is given. This isolable intermediate subsequently rearranges via a sequential isocyanate ring opening and a cyclisation process to a urea derivative which finally cyclized to the indolo[3,2-c]quinolin-6-ones. The urea derivative could be prepared separately and cyclized selectively to indolo[3,2-c]quinolin-6-one. Reaction of N-acetylisatin with 2-aminobenzylamine at room temperature yielded the 1,4-benzodiazepinone 3-(2-acetamidophenyl)-1,5-dihydro-1,4-benzodiazepin-2-one whereas its isomer 2(2-acetamidophenyl)-4,5-dihydro-1,4-benzodiazepin-3-one was obtained from 2-(2-acetylaminophenyl)-N-(2-aminobenzyl)-2-oxoacetamide in acetic acid at room temperature. The previously unknown linear isomer of indolo[3,2-c]quinolin-6-one, i.e. indolo[2,3-b]quinolin-11-one, has been prepared by thermal (260°C) cyclization of methyl 2-phenylamino indole-3-carboxylate, which in turn was prepared in two steps from methyl indole-3-carboxylate.
- Bergman, Jan,Engqvist, Robert,St?lhandske, Claes,Wallberg, Hans
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p. 1033 - 1048
(2007/10/03)
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- Synthesis of indoloquinolones, triazoloindoloquinolines and its derivatives
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1H,2H-2-Oxo-4-hydrazinoquinolines 1a-e on treatment with cyclohexanone give corresponding 1H,2H-2-oxo-4-quinolinylcyclohexanonehydrazones 2a-e. Thermal Fischer indolization of 2a-e yield 5,6-dihydro-11H-6-oxo-indolo[3,2-c]quinoline 3a-e. Chlorination of 3a-e affords the corresponding chloro compounds 11H-6-chloroindolo [3,2-c]quinolines 4a-e, which on treatment with hydrazine hydrate give 11H-6-indolo [3,2-c]quinolinylhydrazines 5a-e. This hydrazone is used as a building block to synthesize corresponding 3-chloro-1′-(11H-indolo[3,2-c]quinolin-6′ yl-amino)-4-(4′-nitrophenyl) azetidin-2-ones 7a-e and 1-phenyl-8H-indolo[3,2-c]quinolin[3′,4′: 1,2] triazoles 8a-e. 1a-e on treatment with p-nitrobenzaldehyde give 4-quinolinylhydrazono-1-4′ -nitrophenyl methanes 9a-e, which on further treatment with chloroacetyl chloride in triethyl amine afford 3-chloro-1′-(4-quinolin-4′ yl-amino)-4-(4′-nitrophenyl)azetidin-2-ones 10a-e. Some of these compounds have been screened for their biological activity.
- Mulwad,Lohar
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p. 1937 - 1942
(2007/10/03)
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- Synthesis and cytotoxic activity evaluation of indolo-, pyrrolo-, and benzofuro-quinolin-2(1H)-ones and 6-anilinoindoloquinoline derivatives.
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Certain indolo-, pyrrolo-, and benzofuro-quinolin-2(1H)-ones 4a,b, 6, 8, 16a-c and 6-anilinoindoloquinoline derivatives 10a,b, 11a,b, 12a,b have been synthesized and evaluated in vitro against a 3-cell lines panel consisting of MCF7 (Breast), NCI-H460 (Lu
- Chen, Yeh-Long,Chung, Chao-Ho,Chen, I-Li,Chen, Po-Hsu,Jeng, Haw-Yaun
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p. 2705 - 2712
(2007/10/03)
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- New methodology for the preparation of pyrrole and indole derivatives via iminophosphoranes:synthesis of pyrrolo[1,2-a]quinoxalines, indolo[3,2-c]quinolines and indolo[1,2-c]quinazolines
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The aza-Wittig reaction of iminophosphorane N-[o-(triphenylphosphoranylidene)amino]-phenyl pyrrole 4 with heterocumulenes leads to functionalized pyrrolo[1,2-a]quinoxalines. Iminophosphorane 19, derived from 2-(o-amino)phenyl indole, reacts under mild con
- Molina, Pedro,Alajarin, Mateo,Vidal, Angel
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p. 1063 - 1078
(2007/10/02)
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- ortho-PYRROLYLPHENYL HETEROCUMULENES: PREPARATION AND CYCLIZATION TO FUSED PYRROLES
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The aza-Wittig reaction of iminophosphoranes derived from o-(1-pyrrolyl)phenyl azide and 2-(o-aminophenyl)indole with isocyanates, isothiocyanates, carbon dioxide or carbon disulfide, lead to functionalized pyrroloquinoxalines and 11H-indolo
- Molina, Pedro,Alajarin, Mateo,Vidal, Angel
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p. 2847 - 2850
(2007/10/02)
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- A Convenient Synthesis of 11H-Indoloquinolones
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11H-Indoloquinolin-6-ones, which are containing the γ-carboline ring system, can be easily synthesized from 4-azido-3-phenyl-2(1H)-quinolones, which are obtained in a two step reaction from 4-hydroxy-3-phenyl-2(1H)-quinolones.Cyclization of the azi
- Stadlbauer, Wolfgang,Karem, Abdul-Salam,Kappe, Thomas
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- Methods for the Synthesis of 4-Azido-2(1H)-quinolones
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4-Hydroxy-2-quinolones 1 are generally found to be converted to the 4-azidocompounds 3 via the 4-chloroquinolones 2, the 4-tosyloxyquinolones 6, or the 4-aminoquinolones 4, respectively.Choice of the reaction conditions and yields depend on the substituen
- Stadlbauer, Wolfgang
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p. 1305 - 1324
(2007/10/02)
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- Synthesis of Indoles and Isoquinolones from Phenylmalonate Heterocycles
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A new synthesis of the indole system has been achieved by cyclodehydrogenation of amino phenylmalonate heterocycles.Thus, the 4-amino coumarins 1a,b or the 4-amino-2-quinolones 1c-g are converted to the indoles 2 with palladium on charcoal in boiling diph
- Stadlbauer, Wolfgang,Kappe, Thomas
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p. 467 - 476
(2007/10/02)
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