- An efficient new route towards biologically active isocryptolepine and γ-carboline derivatives using an intramolecular thermal electrocyclization strategy
-
An efficient and short route is established for biologically active 11H-indolo[3,2-c]quinoline 1, naturally occurring antiplasmodial isocryptolepine 2 and 5-methyl-11H-indolo[3,2-c]quinoline-5-inium iodide 3 using intramolecular thermal electrocyclization
- Hingane, Dattatray G.,Kusurkar, Radhika S.
-
-
Read Online
- Synthesis of Benzofuroquinolines via Phosphine-Free Direct Arylation of 4-Phenoxyquinolines in Air
-
A palladium-catalysed, phosphine-free, direct arylation of 4-phenoxyquinolines, in air is described. Using an intramolecular approach, the ring-closed products are formed in yields of up to 95 %. This approach allows access to a range of benzofuroquinolines. An array of functional groups on both the quinoline and phenoxy rings are tolerated.
- Shanahan, Rachel M.,Hickey, Aobha,Reen, F. Jerry,O'Gara, Fergal,McGlacken, Gerard P.
-
-
Read Online
- Synthesis of isocryptolepine analogues and their structure-activity relationship studies as antiplasmodial and antiproliferative agents
-
Novel isocryptolepine analogues have been conveniently synthesized and evaluated for antimalarial and antiproliferative activities. We have found 3-fluoro-8-bromo-isocryptolepine (1n) to have the highest activities against chloroquine-resistant K1, chloro
- Aroonkit, Pasuk,Thongsornkleeb, Charnsak,Tummatorn, Jumreang,Krajangsri, Suppachai,Mungthin, Mathirut,Ruchirawat, Somsak
-
-
Read Online
- Access to γ-Carbolines: Synthesis of Isocryptolepine
-
A new method to synthesize γ-carboline derivatives has been developed starting from 3,5-dibromo-4-pyridinamine by monoarylation using the Suzuki–Miyaura cross-coupling reaction followed by the base-mediated ring closure to pyrrole formation. Synthesis of
- Akitake, Masahiro,Miyoshi, Kohei,Noda, Shizuki,Sonoda, Motohiro,Tanimori, Shinji
-
p. 17727 - 17737
(2021/12/17)
-
- Triflic acid-mediated N-heteroannulation of β-anilino-β-(methylthio)acrylonitriles: a facile synthesis of 4-amino-2-(methylthio)quinolines
-
Various functionalised 4-amino-2-(methylthio)quinolines are synthesised through triflic acid-mediated N-heteroannulation of α-functionalized-β-anilino-β-(methylthio)acrylonitriles for the first time. The N-heteroannulation process is highly chemoselective and has mild reaction conditions. However, this process fails in the absence of the β-methylthio group in the acrylonitriles. In addition, a new double N-heteroannulation process is demonstrated to synthesise indolo[3,2-c]quinolines from non-heterocyclic precursors. Natural product isocryptolepine is synthesised in four steps from an acyclic precursor.
- Bandyopadhyay, Debashruti,Panigrahi, Adyasha,Peruncheralathan, S.,Radhakrishnan, Divya,Thirupathi, Annaram
-
p. 8544 - 8553
(2021/10/20)
-
- Synthesis and evaluation of the tetracyclic ring-system of isocryptolepine and regioiso-mers for antimalarial, antiproliferative and antimicrobial activities
-
A series of novel quinoline-based tetracyclic ring-systems were synthesized and evaluated in vitro for their antiplasmodial, antiproliferative and antimicrobial activities. The novel hydroiodide salts 10 and 21 showed the most promising antiplasmodial inhibition, with compound 10 displaying higher selectivity than the employed standards. The antiproliferative assay revealed novel pyridophenanthridine 4b to be significantly more active against human prostate cancer (IC50 = 24 nM) than Puromycin (IC50 = 270 nM) and Doxorubicin (IC50 = 830 nM), which are used for clinical treatment. Pyridocarbazoles 9 was also moderately effective against all the employed cancer cell lines and moreover showed excellent biofilm inhibition (9a: MBIC = 100 μM; 9b: MBIC = 100 μM).
- Albrigtsen, Marte,Andersen, Jeanette H.,Avery, Vicky M.,H?heim, Katja S.,Helgeland, Ida T. Urdal,Kennedy, Emily K.,Lauga, Clémence,Lindb?ck, Emil,Matringe, Théodora,Sydnes, Magne O.,Tan, Kah Ni
-
-
- Substrate or Solvent-Controlled PdII-Catalyzed Regioselective Arylation of Quinolin-4(1H)-ones Using Diaryliodonium Salts: Facile Access to Benzoxocine and Aaptamine Analogues
-
Regioselective C3, C5, and C8 arylation of quinolin-4(1H)-ones have been accomplished either by substrate-control or by tuning the reaction solvent. A variety of aryl(mesityl)iodonium triflates could smoothly deliver arylated products in good to excellent yields. Additionally, it offers great flexibility by arylating medicinally potent quinolone related heterocycles such as acridin-9(10H)-one, and phenanthridin-6(5H)-one under standard reaction conditions. This strategy was further extended with diphenyleneiodonium triflate to access oxacine fused quinolines. The post-modifications of synthesized products enhance the further utility of this protocol in organic synthesis. To the best of our knowledge, this is the first report on C5 arylation of quinolin-4(1H)-ones using iodine(III) reagents.
- Mehra, Manish K.,Sharma, Shivani,Rangan, Krishnan,Kumar, Dalip
-
supporting information
p. 2409 - 2413
(2020/03/16)
-
- Synthesis of 11H-indolo[3,2-c]quinolines by SnCl4-catalyzed cyclization of indole-3-carbaldehyde oximes
-
A new method for synthesizing 11H-indolo[3,2-c]quinolines by SnCl4-catalyzed intramolecular electrophilic amination of 2-arylindole-3-carbaldehyde O-acetyl oximes was developed.
- Aksenov,Gasanova,Prokonov, F. Yu.,Aksenov,Abakarov,Aksenov
-
p. 2262 - 2270
(2020/02/15)
-
- Novel convenient one-pot method for the synthesis of indoloquinolines
-
A novel one-pot method based on the sequence of the Fisher reaction between nitroacetophenone and phenylhydrazines, the reduction with metallic tin directly in polyphosphoric acid, and acylation has been developed for the synthesis of indoloquinolines. Th
- Aksenov,Gasanova,Abakarov,Aksenova,Aksenov
-
p. 836 - 840
(2019/06/03)
-
- A nitroalkane-based approach to one-pot three-component synthesis of isocryptolepine and its analogs with potent anti-cancer activities
-
A second generation polyphosphoric acid-mediated one-pot three-component synthesis of indoloquinoline scaffold is developed. This improved version of the process involves electrophilically activated nitroalkanes for the installation of strategic C-C and C-N bonds and ring C assembly. This modification allows the elimination of unnecessary solvent change operations and all steps are carried out in a true, uninterrupted one-pot manner. A further improvement involves the possibility to install an ortho-amino group in situ. A synthetic application of this method is showcased by the concise synthesis of an isocryptolepine alkaloid and its synthetic analogs with potent anticancer activities.
- Aksenov, Nicolai A.,Aksenov, Alexander V.,Kornienko, Alexander,De Carvalho, Annelise,Mathieu, Véronique,Aksenov, Dmitrii A.,Ovcharov, Sergei N.,Griaznov, Georgii D.,Rubin, Michael
-
p. 36980 - 36986
(2018/11/23)
-
- Dimethyl Sulfoxide Involved One-Pot Synthesis of Quinoxaline Derivatives
-
An efficient, green, and novel method for the synthesis of N-heterocycle-fused quinoxalines is reported herein. Dimethyl sulfoxide was used as both a reactant and a solvent in this reaction. A wide range of products in moderate to excellent yields were obtained, including pyrrolo[1,2-a]quinoxalines, indolo[1,2-a]quinoxalines, 1H-pyrrolo[3,2-c]quinolines, and benzo[4,5]imidazo[1,2-c]quinazolines.
- Xie, Caixia,Zhang, Zeyuan,Li, Danyang,Gong, Jian,Han, Xushuang,Liu, Xuan,Ma, Chen
-
p. 3491 - 3499
(2017/04/11)
-
- One-Pot, Three-Component Assembly of Indoloquinolines: Total Synthesis of Isocryptolepine
-
Indolo[3,2-c]quinolones have been efficiently synthesized via an acid-mediated, one-pot, three-component condensation of arylhydrazines, o-aminoacetophenones, and triazines or nitriles. The synthetic application of this method is showcased by the concise synthesis of isocryptolepine alkaloid and a series of its synthetic analogues with demonstrated cancer cell antiproliferative activities.
- Aksenov, Alexander V.,Aksenov, Dmitrii A.,Orazova, Naila A.,Aksenov, Nicolai A.,Griaznov, Georgii D.,De Carvalho, Annelise,Kiss, Robert,Mathieu, Véronique,Kornienko, Alexander,Rubin, Michael
-
p. 3011 - 3018
(2017/03/23)
-
- Indole [3,2-c] quinoline compound or its pharmaceutically acceptable salts and its preparation method and application
-
The invention discloses indole[3,2-c]quinoline compounds represented by formula I or pharmaceutically acceptable salts thereof, and a preparation method and an application thereof, and belongs to the technical field of the pharmaceutical chemistry. The in
- -
-
Paragraph 0036; 0052-0055
(2016/10/10)
-
- Regioselective Synthesis of Indolo[1,2-c]quinazolines and 11H-Indolo[3,2-c]quinolines via Copper-Catalyzed Cascade Reactions of 2-(2-Bromoaryl)-1H-indoles with Aldehydes and Aqueous Ammonia
-
Highly selective and convenient synthesis of indolo[1,2-c]quinazolines and 11H-indolo[3,2-c]quinolines through copper-catalyzed one-pot cascade reactions of 2-(2-bromoaryl)-1H-indoles with aldehydes and aqueous ammonia has been achieved. Notably, the regioselectivity was easily controlled by tuning the reaction conditions. Compared with literature methods, the present protocol features easily controlled selectivity, readily available starting materials, good functional group tolerance, and simple operation procedures.
- Guo, Shenghai,Tao, Li,Zhang, Wenwen,Zhang, Xinying,Fan, Xuesen
-
p. 10955 - 10964
(2015/11/18)
-
- Rapid synthesis of fused N-heterocycles by transition-metal-free electrophilic amination of arene C-H bonds
-
We disclose an efficient and operationally simple protocol for the preparation of fused N-heterocycles starting from readily available 2-nitrobiaryls and PhMgBr under mild conditions. More than two dozen N-heterocycles, including two bioactive natural products, have been synthesized using this method. A stepwise electrophilic aromatic cyclization mechanism was proposed by DFT calculations. Controlled fusion: A transition-metal-free, low-temperature, and regioselective intramolecular amination of aromatic C(sp2)-H bonds provides fused N-heterocycles. This reaction is operationally simple and scalable (1-10 mmol) and the scope of substrates is wide (see scheme). Density functional calculations indicate that a stepwise electrophilic aromatic cyclization mechanism may be operative.
- Gao, Hongyin,Xu, Qing-Long,Yousufuddin, Muhammed,Ess, Daniel H.,Kuerti, Laszlo
-
supporting information
p. 2701 - 2705
(2014/03/21)
-
- A concise synthesis of indoloquinoline skeletons applying two consecutive Pd-catalyzed reactions
-
The indoloquinoline alkaloids cryptolepine (1), neocryptolepine (2), isocryptolepine (3), and isoneocryptolepine (4) are important tools in traditional medicine. Now, their precursors 1a-4a were synthesized in two steps starting from the corresponding bromo-iodoquinolines. Our strategy is based on palladium-catalyzed reactions, applying regioselective Buchwald-Hartwig amination on 2,3- and 3,4-dihaloquinolines followed by an intramolecular Heck-type reaction. Both steps were carried out under microwave irradiation.
- Bogányi, Borbála,Kámán, Judit
-
p. 9512 - 9519
(2013/10/08)
-
- From biomass to medicines. A simple synthesis of indolo[3,2-c]quinolines, antimalarial alkaloid isocryptolepine, and its derivatives
-
Indolo[3,2-c]quinolines are pharmacologically attractive class of heterocyclic compounds. The method of their synthesis, based on transformation of furfural, which is a large-scale product of treatment of biomass including agricultural and forestry wastes, has been developed. This method was utilized for the total synthesis of antimalarial alkaloid isocryptolepine and its derivatives.
- Uchuskin, Maxim G.,Pilipenko, Arkady S.,Serdyuk, Olga V.,Trushkov, Igor V.,Butin, Alexander V.
-
p. 7262 - 7265
(2012/09/22)
-
- Acid-promoted rearrangement of arylmethyl azides: Applications toward the synthesis of N-arylmethyl arenes and polycyclic heteroaromatic compounds
-
An acid-promoted Aubé-Schmidt's rearrangement of arylmethyl azides provides a useful in situ iminium ion intermediate, which can be efficiently trapped by various nucleophiles. We report here the reaction of this iminium ion with aromatic nucleophiles to
- Tummatorn, Jumreang,Thongsornkleeb, Charnsak,Ruchirawat, Somsak
-
p. 4732 - 4739
(2012/07/28)
-
- A novel total synthesis of isocryptolepine based on a microwave-assisted tandem Curtius rearrangement and aza-electrocyclic reaction
-
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
-
p. 4274 - 4279
(2012/07/16)
-
- Facile assembly of 11 H -indolo[3,2-c]quinoline by a two-step protocol involving a regioselective 6- endo -cyclization promoted by the hendrickson reagent
-
An expedient approach was developed to construct the 11H-indolo[3,2-c] quinoline scaffold starting from acyclic alkyne substrates. The five- and six-membered nitrogen-containing rings in the tetracyclic skeleton were elaborated efficiently by gold(III)-ca
- Xu, Min,Hou, Qiwen,Wang, Shaozhong,Wang, Huaqin,Yao, Zhu-Jun
-
p. 626 - 634
(2011/04/15)
-
- Synthesis and antimalarial evaluation of novel isocryptolepine derivatives
-
A series of mono- and di-substituted analogues of isocryptolepine have been synthesized and evaluated for in vitro antimalarial activity against chloroquine sensitive (3D7) and resistant (W2mef) Plasmodium falciparum and for cytotoxicity (3T3 cells). Di-h
- Whittell, Louise R.,Batty, Kevin T.,Wong, Rina P.M.,Bolitho, Erin M.,Fox, Simon A.,Davis, Timothy M.E.,Murray, Paul E.
-
p. 7519 - 7525
(2012/01/05)
-
- A flexible synthesis of indoles from ortho -substituted anilines: A direct synthesis of isocryptolepine
-
The reaction of anilines bearing a benzylic activating group in the ortho position with aromatic aldehydes or α,β-unsaturated aldehydes results in an efficient synthetic route to substituted indoles. Georg Thieme Verlag Stuttgart · New York.
- Kraus, George A.,Guo, Haitao,Kumar, Ganesh,Pollock Iii, Gerald,Carruthers, Heather,Chaudhary, Divya,Beasley, Jonathan
-
scheme or table
p. 1386 - 1393
(2010/07/16)
-
- New route to the synthesis of the isocryptolepine alkaloid and its related skeletons using a modified Pictet-Spengler reaction
-
A new route to the synthesis of the isocryptolepine alkaloid with antimalarial activity using a modified Pictet-Spengler reaction has been devised. The strategy was then used to generate libraries based on three structural variants of the alkaloid. Compounds based on these three variants in general were accessed in three steps through a modified Pictet-Spengler cyclization reaction as the key step. The C-2-, C-3-, or N-1-linked (aminoaryl)indoles (8, 12, 13) required for cyclization were obtained by treating the corresponding indoles with o-halonitrobenzene using either nucleophilic re-placement or Pd-based chemistry (Heck/Suzuki reaction) followed by reduction of the nitroaryl functionality. The substrates 8, 12, and 13 were then subjected to the Pictet-Spengler reaction to furnish polycyclic structures, indolo-quinolines 4 and 19 and indolo-quinoxalines 20 with three-point diversity in high yields and purities. One of the indolo-quinolines 4a after treatment with CH3I furnished the isocryptolepine alkaloid in excellent yield. Wiley-VCH Verlag GmbH & Co. KGaA, 2009.
- Agarwal, Piyush K.,Sawant, Devesh,Sharma, Sunil,Kundu, Bijoy
-
experimental part
p. 292 - 303
(2009/06/21)
-
- Auto-tandem catalysis: Synthesis of substituted 11H-indolo [3,2-c]quinolines via palladium-catalyzed intermolecular C-N and intramolecular C-C bond formation
-
D-Ring substituted 11H-indolo[3,2-c]quinolines (4) have been prepared via auto-tandem consecutive intermolecular Buchwald-Hartwig reaction and intramolecular palladium-catalyzed arylation on 4-chloroquinoline (1) with N-unsubstituted 2-chloroanilines (2).
- Meyers, Caroline,Rombouts, Geert,Loones, Kristof T. J.,Coelho, Alberto,Maes, Bert U. W.
-
supporting information; experimental part
p. 465 - 470
(2009/04/10)
-
- Heteroatom directed photoannulation: synthesis of indoloquinoline alkaloids: cryptolepine, cryptotackieine, cryptosanguinolentine, and their methyl derivatives
-
A three-step synthesis of indoloquinoline alkaloids is described. The reaction of 2,3 and 4-substituted haloquinolines with anilines afforded the respective anilinoquinolines, which upon photocyclization gave the indoloquinolines. By regioselective methylation on quinoline nitrogen, furnished the alkaloids cryptotackieine, cryptosanguinolentine, cryptolepine, and the synthetic isomer isoneocryptolepine. Their methyl derivatives were also synthesized in search of new antiplasmodial drugs and DNA intercalating agents.
- Dhanabal,Sangeetha,Mohan
-
p. 6258 - 6263
(2007/10/03)
-
- Synthesis of isocryptolepine via a Pd-catalyzed 'amination-arylation' approach
-
Isocryptolepine (cryptosanguinolentine) has been synthesized in three steps via a new approach starting from commercially available 4-chloroquinoline and 2-chloroaniline. The new methodology consists of two consecutive palladium-catalyzed reactions; a sel
- Jonckers, Tim H. M.,Maes, Bert U. W.,Lemière, Guy L. F.,Rombouts, Geert,Pieters, Luc,Haemers, Achiel,Dommisse, Roger A.
-
p. 615 - 618
(2007/10/03)
-
- A photochemical route to synthesize cryptosanguinolentine
-
A synthesis of an indoloquinoline based alkaloid, isolated from Cryptolepis sanguinolenta is reported. The formation of a Schiff base between aniline and indole-3-carbaldehyde and subsequent photochemical transformation afforded the desired alkaloid.
- Kumar, R.Nandha,Suresh,Mohan
-
p. 3327 - 3328
(2007/10/03)
-
- A Convenient Synthesis of Two New Indoloquinoline Alkaloids
-
A concise synthesis of two new indoloquinoline-based alkaloids (1 and 2), isolated from Cryptolepis sanguinolenta, is reported. The palladium-catalyzed cross-coupling reaction of 3-bromoquinoline derivatives with N-pivaloylamino phenylboronic acid gave th
- Timári, Géza,Soós, Tibor,Hajós, Gy?rgy
-
p. 1067 - 1068
(2007/10/03)
-
- Synthesis and DNA binding properties of γ-carbolinium derivatives and benzologues
-
The 5H-pyrido[4,3-b]indole, 11H-indolo[3,2-c]quinoline, 5H-benzo[f]pyrido[4,3-b]indole, and 13H-benz[5,6]indolo[3,2-c]quinoline heteroaromatic nuclei have been synthesized by the Graebe-Ullmann method by classical heating or under microwave irradiation. These tri-, tetra-, and pentacyclic compounds were transformed into the corresponding cationic derivatives by N-alkylation, and the DNA-binding properties of the resulting cationic systems were examined using UV-vis spectroscopy, viscometric determinations, and molecular modeling techniques. The tetracyclic cations were transformed into bis-salts by means of a diethyl bispiperidine rigid chain and a more flexible polyamide linker, but the low solubility of these bis-salts made the study of their bisintercalating properties difficult.
- Molina,Vaquero,Garcia-Navio,Alvarez-Builla,De Pascual-Teresa,Gago,Rodrigo,Ballesteros
-
p. 5587 - 5599
(2007/10/03)
-
- Structure-activity relationships of antimalarial indoloquinolines
-
Structure-activity relationships have been ascertained and chemical metodology developed for a series of antimalarial 3-chloroindoloquinoline-5-oxides.The basic side chain as well as the ring N-oxide are critical for antimalarial activity as is a bromine or chlorine in position 3.Substitution at positions 7,8,9,10 in not essential, although the most potent analog in our studies was the 8-nitro compound 4vv. indoloquinolines / antimalarial agents
- Werbel, L. M.,Kesten, S. J.,Turner, W. R.
-
p. 837 - 852
(2007/10/02)
-
- A Convenient Synthesis of 11H-Indoloquinolones
-
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
-
-
- Synthetic Routes to Arylpyrido-azepines and -azepines.
-
9-Phenyl-6-methoxy-5H-pyridoazepine and 9-phenyl-7-methoxy-5H-pyridoazepine have been obtained by arylation (PhLi) of 6,9-dimethoxy-5H-pyridoazepine and by photolysis of 6-azido-9-phenylquinoline in potassium methoxide-methanol-dioxan
- Schofield, Joseph,Smalley, Robert K.,Scopes, David I. C.,Patel, Dalpat I.
-
p. 1401 - 1426
(2007/10/02)
-