- Dithiolation indolizine exerts viability suppression effects on A549 cells via triggering intrinsic apoptotic pathways and inducing G2/M phase arrest
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Indolizine derivatives have been reported for the treatment of numerous diseases. However, few studies were carried out for non-small cell lung cancer (NSCLC). We synthesized series of indolizine compounds. The results of MTT assay showed compound 8 (C8) markedly inhibited the proliferation of A549 cells, however, C8 (15, 30 μg/mL) had little cytotoxicity in other cell lines (SH-SY5Y, HepG2, and BEAS-2B cells), Hoechst staining and JC-1 staining showed that C8 induced changes in the nucleus morphology, increased the loss in mitochondrial membrane potential in A549 cells. The results of flow cytometry manifested that cell cycle of the cells was arrested in the G2 / M phase by C8, ROS levels and the proportion of apoptosis of cells increased. We performed western blotting analysis to detect the expression levels of apoptosis and cycle-related proteins. These results validated that the apoptosis of cells was triggered by endoplasmic reticulum stress (ERS) and the PI3K/Akt-mediated mitochondrial pathway collaboratively. Besides, the utilization of PI3K/Akt inhibitors and p53 inhibitors further proves the above argument and C8-induced cycle arrest of A549 cells is majorly regulated by p53. C8 induced the accumulation of ROS contents involved in mitochondrial damage. The proliferation of A549 cells was inhibited after treatment with the compound, which induced apoptosis and cycle arrest of cells. It is suggested that C8(dithiolation indolizine) is a potential candidate compound against non-small cell lung cancer.
- Li, Guanting,Wu, Xianwei,Sun, Peng,Zhang, Zhiyang,Shao, Enxian,Mao, Jianping,Cao, Hua,Huang, Hongliang
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- Electrochemical diselenylation of indolizines: Via intermolecular C-Se formation with 2-methylpyridines, α-bromoketones and diselenides
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An efficient electrochemical system for the construction of diselenytlated indolizines from available pyridines, ketones and diselenides under undivided electrolytic conditions was developed. No external oxidants and transition-metal catalysts are needed for achieving this three-component tandem reaction realizing C-C, C-N and C-Se bond formations.
- Li, Junxuan,Liu, Xiang,Deng, Jiadi,Huang, Yingshan,Pan, Zihao,Yu, Yue,Cao, Hua
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- Photocatalytic Synthesis of 3-Sulfanyl- and 1,3-Bis(sulfanyl)indolizines Mediated by Visible Light
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A metal-free method for the synthesis of 3-sulfanyl indolizines from thiols and 2-arylindolizines, is reported. The reaction is mediated by eosin Y under blue LED light irradiation and uses atmospheric oxygen as oxidant. By the use of a catalytic amount of I2, the corresponding 1,3-bis-sulfanyl indolizines are obtained, in good yields.
- Gomes, Caroline S.,Lenard?o, Eder J.,Monzon, Loana I.,Penteado, Filipe,Perin, Gelson,Silveira, Claudio C.
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- Transition-Metal-Free Regioselective Cross-Coupling: Controlled Synthesis of Mono- or Dithiolation Indolizines
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An efficient transition-metal-free regioselective C-H/S-H cross-coupling of indolizines with thiols has been developed for the first time to describe a workable route to indolizine thioethers. This finding provides a new method and more straightforward pathway for controllable synthesis of mono- or dithiolation indolizines that are otherwise difficult to obtain by the literature methods. The reaction exhibits good functional group tolerance and high efficiency and affords the products in good to excellent yields.
- Li, Bin,Chen, Zhiyu,Cao, Hua,Zhao, Hong
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- Oxidation Potential-Guided Electrochemical Radical-Radical Cross-Coupling Approaches to 3-Sulfonylated Imidazopyridines and Indolizines
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Oxidation potential-guided electrochemical radical-radical cross-coupling reactions between N-heteroarenes and sodium sulfinates have been established. Thus, simple cyclic voltammetry measurement of substrates predicts the likelihood of successful radical-radical coupling reactions, allowing the simple and direct synthetic access to 3-sulfonylated imidazopyridines and indolizines. The developed electrochemical radical-radical cross-coupling reactions to sulfonylated N-heteroarenes boast the green synthetic nature of the reactions that are oxidant- and metal-free.
- Kim, Wansoo,Kim, Hun Young,Oh, Kyungsoo
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p. 15973 - 15991
(2021/07/26)
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- Mechanochemical Synthesis of 1,2-Diketoindolizine Derivatives from Indolizines and Epoxides Using Piezoelectric Materials
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A simple and efficient mechanochemical-induced approach for the synthesis of 1,2-diketoindolizine derivatives has been developed. BaTiO3 was used as the piezoelectric material in this transformation. This method features no usage of solvent, simple experimental operation, scalable potential, and high conversion efficiency, which make it attractive and practical.
- Wang, Yumei,Zhang, Ziwu,Deng, Lichan,Lao, Tianfeng,Su, Zhengquan,Yu, Yue,Cao, Hua
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supporting information
p. 7171 - 7176
(2021/09/14)
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- Regioselective C-H dithiocarbamation of indolizines with tetraalkylthiuram disulfide under metal-free conditions
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An efficient and straightforward metal-free regioselective C-H dithiocarbamation of indolizines with tetraalkylthiuram disulfide has been described. A series of indolizine-dithiocarbamate derivatives were easily accessed in moderate to good yields with a broad scope. In addition, imidazo[1,2-a]pyridines were also well tolerated to afford diverse imidazoheterocycle-dithiocarbamate products, which are expected to be utilized for drug discovery. Of note, the reaction could be readily scaled up, and shows its practical value in organic synthesis.
- Cao, Hua,Lin, Jiatong,Liu, Xiang,Song, Dan,Zhan, Haiying,Zhang, Zemin,Zhuang, Canzhan
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supporting information
p. 5284 - 5288
(2021/06/28)
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- Synthesis of 1,2-Dicyano-3-arylcycl[3.2.2]azines – First 1,2-Dicarbonitriles Based on Cyclazine Heterocycle
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The first 1,2-dicarbonitriles have been prepared for cyclazine systems. In particular, a synthetic procedure to 1,2-dicyano-3-arylcycl[3.2.2]azines has been developed. Unexpected chlorination of 3-arylcycl[3.2.2]azine-1,2-dicarboxylic acid derivatives by thionyl chloride at 4-position was found, which according to theoretical considerations can proceed by the electrophilic (SEAr) mechanism. The compounds are blue fluorophores in 450–480 nm region with quantum yields in toluene of ca. 30 % for non-chlorinated derivatives, which decrease to 3–4 % for chlorinated ones.
- Chernyak, Alexander V.,Kalashnikov, Valery V.,Kazachenko, Vladimir P.,Pushkarev, Victor E.,Simakov, Anton O.,Simonov, Sergey V.,Starikov, Andrei S.,Tarakanov, Pavel A.,Tkachev, Valery V.,Tomilova, Larisa G.,Yarkov, Alexander V.,Zhurkin, Fedor E.
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supporting information
p. 5852 - 5856
(2020/09/21)
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- Enantioselective Synthesis of 3-Allylindolizines via Sequential Rh-Catalyzed Asymmetric Allylation and Tschitschibabin Reaction
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The first highly regio- and enantioselective synthesis of 3-allylindolizines has been developed by the sequential Rh-catalyzed asymmetric allylation and Tschitschibabin reaction. Above the 20:1 branch/linear ratio, up to a 96% yield and 99% ee could be obtained with the help of tert-butyl-substituted chiral bisoxazolinephosphine ligand. In situ generated highly nucleophilic 2-alkylpyridinium ylides are utilized to undergo the asymmetric alkylation reaction before cyclization.
- Li, Ke,Li, Changkun
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supporting information
p. 9456 - 9461
(2020/12/21)
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- NH4I-catalyzed C–S bond formation via an oxidation relay strategy: Efficient access to dithioether decorated indolizines
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An efficient NH4I-catalyzed C–H/S–H cross-coupling reaction of indolizines with thiols is reported. Compared to previous methods, this environmentally friendly oxidation relay strategy uses O2 as an oxidant to afford dithioether decorated indolizines in up to 98% yield. Promising results have been obtained, indicating the high applicability and atom economy of this method.
- Zhu, Yu,Yang, Liechao,Fang, Liyun,Du, Xiaofan,Chen, Keda,Yu, Chuanming,Jiang, Xinpeng
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supporting information
(2020/09/15)
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- Visible-Light-Induced Regioselective Dicarbonylation of Indolizines with Oxoaldehydes via Direct C-H Functionalization
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A metal-free system for regioselective dehydrogenative cross-couplings between indolizines and oxoaldehydes catalyzed by visible light under mild conditions has been described. As an atom economical and eco-friendly protocol, the reaction proceeds in good yields using inexpensive, readily available visible-light sources and the environmentally friendly oxidant oxygen. Various valuable 1,2-dicarbonyl derivatives attached to an indolizine core were easily accessed by the direct dicarbonylation of the sp2 C-H bond.
- Teng, Lili,Liu, Xiang,Guo, Pengfeng,Yu, Yue,Cao, Hua
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supporting information
p. 3841 - 3845
(2020/05/08)
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- Synthesis of Pyrrolo[2,1,5- cd]indolizine Rings via Visible-Light-Induced Intermolecular [3+2] Cycloaddition of Indolizines and Alkynes
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A range of indolizine smoothly underwent visible-light-induced intermolecular [3+2] annulations with internal alkynes to afford pyrrolo[2,1,5-cd]indolizine in good to excellent yields with high regioselectivity. Through this cascade reaction, a series of fluoroactive fused indolizines with a large π-system were conveniently synthesized. The usage of visible light as energy source with air as a stoichiometric oxidant under simple conditions makes this process attractive and practical.
- Zhang, Yu,Yu, Yue,Liang, Bing-Bing,Pei, Yong-Yan,Liu, Xiang,Yao, Hua-Gang,Cao, Hua
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p. 10719 - 10727
(2020/09/18)
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- Palladium(II)/Copper(II)-Catalyzed C–H Sulfidation or Selenation of Arenes Leading to Unsymmetrical Sulfides and Selenides
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A novel palladium(II)/copper(II)-catalyzed sulfidation of the C–H bond in electron-rich arenes and in pentafluorobenzene with disulfides was developed. This catalytic system can be used to efficiently produce various types of either unsymmetrical aryl sulfides or alkyl aryl sulfides. The present protocol could also be applied to the direct preparation of unsymmetrical aryl selenides via C–H selenation.
- Nishino, Kota,Tsukahara, Shouya,Ogiwara, Yohei,Sakai, Norio
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p. 1588 - 1593
(2019/02/09)
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- A visible-light-induced intermolecular [3 + 2] alkenylation-cyclization strategy: Metal-free construction of pyrrolo[2,1,5-cd] indolizine rings
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A simple and efficient visible-light-induced intermolecular [3 + 2] alkenylation-cyclization process has been developed. This reaction provided an unprecedented metal-free double C(sp2)-H bond oxidation coupling of indolizines with electron-deficient alkenes. Through this cascade reaction, a series of pyrrolo[2,1,5-cd]indolizine derivatives with a large π-system were synthesized. Furthermore, this approach features easily available starting materials, good functional group tolerance, step-economy, high efficiency and mild conditions.
- Liang, Yaofeng,Teng, Lili,Wang, Yajun,He, Qiuxing,Cao, Hua
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supporting information
p. 4025 - 4029
(2019/08/07)
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- Synthesis, photophysical, and electrochemical properties of 2,5-diaryl-indolizines
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A variety of novel 2,5-diaryl-indolizines have been prepared through the palladium-catalyzed cross-coupling reactions of organozinc reagents prepared from 2-aryl-indolizines with aromatic halides. The photophysical properties of representative compounds indicate that the 2,5-diaryl-indolizines are promising candidates to be used in optoelectronic devices and biomolecular labeling. In addition, cyclic voltammetry studies of some nitrophenyl-substituted indolizines have shown evidences of an oxidation process without the correspondent reduction peak suggesting a dimerization reaction.
- Amaral, M?nica F.Z.J.,Deliberto, Laila A.,De Souza, Camila R.,Naal, Rose M.Z.G.,Naal, Zeki,Clososki, Giuliano C.
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p. 3249 - 3258
(2014/05/06)
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- Synthesis of functionalized indolizines via copper-catalyzed annulation of 2-alkylazaarenes with α,β-unsaturated carboxylic acids
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A novel copper-catalyzed annulation of 2-alkylazaarenes with α,β-unsaturated carboxylic acids has been accomplished. This reaction featuring C-H olefination and decarboxylative amination processes provides a concise access to C-2 arylated indolizines from simple and readily available starting materials.
- Yang, Yuzhu,Xie, Chunsong,Xie, Yongju,Zhang, Yuhong
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supporting information; experimental part
p. 957 - 959
(2012/04/04)
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- Microwave promoted synthesis of cycl[3.2.2]azines in water via a new three-component reaction
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A microwave-promoted and base-catalyzed synthesis of cycl[3.2.2]azines is accomplished in water via a three-component reaction (3-CR) of 2-picoline, α-bromoacetophenone and alkyne. The extension of the methodology to the synthesis of steroidal and carbocyclic cycl[3.2.2]azine is also reported.
- Gogoi, Shyamalee,Dutta, Mandakini,Gogoi, Junali,Boruah, Romesh Chandra
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experimental part
p. 813 - 816
(2011/03/18)
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- 2- [ (2-SUBSTITUTED) -IND0LIZIN-3-YL] -2-OXO-ACETAMIDE DERIVATIVES AS ANTIFUNGAL AGENTS
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The invention provides compounds of formula (I), and pharmaceutically acceptable salts thereof wherein: Rl, R2, R3, R4, R5, R6, R7, X and X1 are as defined herein. These compounds are useful in the manufacture of medicaments for use in the prevention or treatment of a fungal disease. Compounds of formula (I), and agriculturally acceptable salts thereof, may also be used as agricultural fungicides.
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Page/Page column 166
(2008/12/05)
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- A mild preparation of substituted indolizines and indole from simple aromatic precursors using (trimethylsilyl)diazomethane
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A mild and convenient synthesis of substituted indolizines from readily available 2-(pyridin-2-yl)acetyl derivatives using (trimethylsilyl)diazomethane is described. The extension of this methodology to the synthesis of indole from 2-aminobenzaldehyde is also reported.
- Zhu, Liusheng,Vimolratana, Marc,Brown, Sean P.,Medina, Julio C.
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p. 1768 - 1770
(2008/09/18)
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- ANTIFUNGAL AGENTS
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Compounds of formula (I), and pharmaceutically acceptable salts thereof, may be used in therapy, for example as antifungal agents: (I) wherein: Rl, R2, R3, R4, R5, R6, R7, X and X1 are as defined herein. Certain compounds of formula (I) are also provided. Compounds of formula (T), and agriculturally acceptable salts thereof, may also be used as agricultural fungicides.
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Page/Page column 42
(2008/06/13)
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- Controlling chemoselectivity-application of DMF di-t-butyl acetal in the regioselective synthesis of 3-monosubstituted indolizines
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Among a number of DMF dialkyl acetals investigated for the regioselective synthesis of 3-acylindolizines, the di-t-butyl acetal, via its iminium intermediate readily formed in situ, provides the highest chemoselectivity for the intermolecular cyclization of picolinium salts. DMF di-t-butyl acetal was applied to the syntheses of a variety of 3-acylated indolizines including alkyl, aryl, and heteroaryl substituents.
- Xia, Zhiqiang,Przewloka, Teresa,Koya, Keizo,Ono, Mitsunori,Chen, Shoujun,Sun, Lijun
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p. 8817 - 8820
(2007/10/03)
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- An improved synthesis of some 5-substituted indolizines using regiospecific lithiation
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Various 2-substituted indolizines can be directly and selectively lithiated in the 5 position and subsequent reactions with different electrophiles lead to some novel classes of indolizines. In particular, previously unknown 5-formyl- and 5-iodoindolizine have been prepared by this way and the molecular structure of 5-formyl-2-phenylindolizine was confirmed by X-Ray analysis. The reactivity of the 5-CHO- and 5-COPh groups toward some nucleophiles has been examined, and some additional classes of derivatives (oximes and alcohols) have been obtained. The possibility of Suzuki cross-coupling of 5-iodoindolizines and boronic acids was proven.
- Kuznetsov, Alexey G.,Bush, Alexander A.,Rybakov, Viktor B.,Babaev, Eugene V.
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p. 1074 - 1083
(2007/10/03)
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- A new approach for the synthesis of fused pyrroles. The synthesis of acyl substituted pyrrolo[1,2-x]azines
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N-Acetonyl- and N-phenacyl quaternary salts of α-methyl substituted heterocycles 16, 17, 21, 23 and 26 were converted with DMFDMA into the corresponding 3-acylpyrrolo[1,2-a]pyridine 18, 7-benzoylpyrrolo[1,2- c]pyrimidine 22, and 6-benzoylpyrrolo[1,2-a]pyrazine derivatives 24 and 27. A concurrent reaction produced methyl and phenyl substituted pyrrolo[1,2- x]azines 19, 20, 25 and 28.
- Copar,Stanovnik,Tisler
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p. 1577 - 1580
(2007/10/02)
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- 2-Methylpyridinium Salts as 1,4-Dinucleophiles. Quinolizinium Salts from the Westphal Condensation
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Condensation of 2-methylpyridinium salts with 1,2-dicarbonyls in the presence of base, yielded 2,3-disubstituted quinolizinium compounds.Results obtained with different pyridinium substrates are discussed.
- Alvarez-Builla, J.,Trigo, G. Gonzales,Ezquerra, J.,Fombella, M.E.
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p. 681 - 685
(2007/10/02)
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