- ZYH005, a novel DNA intercalator, overcomes all-trans retinoic acid resistance in acute promyelocytic leukemia
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Despite All-trans retinoic acid (ATRA) has transformed acute promyelocytic leukemia (APL) from the most fatal to the most curable hematological cancer, there remains a clinical challenge that many high-risk APL patients who fail to achieve a complete molecular remission or relapse and become resistant to ATRA. Herein, we report that 5-(4-methoxyphenethyl)-[1, 3] dioxolo [4, 5-j] phenanthridin-6(5H)-one (ZYH005) exhibits specific anticancer effects on APL and ATRA-resistant APL in vitro and vivo, while shows negligible cytotoxic effect on non-cancerous cell lines and peripheral blood mononuclear cells from healthy donors. Using single-molecule magnetic tweezers and molecule docking, we demonstrate that ZYH005 is a DNA intercalator. Further mechanistic studies show that ZYH005 triggers DNA damage, and caspase-dependent degradation of the PML-RARa fusion protein. As a result, APL and ATRA-resistant APL cells underwent apoptosis upon ZYH005 treatment and this apoptosis-inducing effect is even stronger than that of arsenic trioxide and anticancer agents including 5-fluorouracil, cisplatin and doxorubicin. Moreover, ZYH005 represses leukemia development in vivo and prolongs the survival of both APL and ATRA-resistant APL mice. To our knowledge, ZYH005 is the first synthetic phenanthridinone derivative, which functions as a DNA intercalator and can serve as a potential candidate drug for APL, particularly for ATRA-resistant APL.
- Tong, Qingyi,You, Huijuan,Chen, Xintao,Wang, Kongchao,Sun, Weiguang,Pei, Yufeng,Zhao, Xiaodan,Yuan, Ming,Zhu, Hucheng,Luo, Zengwei,Zhang, Yonghui
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- Synthesis of phenanthridinones from N-methoxybenzamides and arenes by multiple palladium-catalyzed C-H activation steps at room temperature
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Many steps make light work: Substituted phenanthridinones can be obtained with high regioselectivity and in very good yields by palladium-catalyzed cyclization reactions of N-methoxybenzamides with arenes (see scheme). The reaction proceeds through multiple oxidative C-H activation and C-C/C-N formation steps in one pot at room temperature, and thus provides a simple method for generating bioactive phenanthridinones. Copyright
- Karthikeyan, Jaganathan,Cheng, Chien-Hong
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- Photoinduced Annulation of N-Phenylbenzamides for the Synthesis of Phenanthridin-6(5H)-Ones
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A general concise method for the synthesis phenanthridin-6(5H)-ones via photoinduced intramolecular annulation of N-phenylbenzamides was developed. Under argon atmosphere and room temperature, phenanthridin-6(5H)-ones were obtained via irradiation N-phenylbenzamides with a 280 nm UV lamp in the presence of methanesulfonic acid in toluene. The mechanism is illustrated and believed to proceed in the order of amides tautomerization, 6π-electric cyclization, [1,5]-H shift, amide-imidine tautomerization, keto-enol tautomerism and evolution hydrogen. (Figure presented.).
- Wang, Nana,Wang, Ding,He, Yun,Xi, Jin,Wang, Tao,Liang, Yong,Zhang, Zunting
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supporting information
p. 1150 - 1155
(2022/02/25)
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- Method for efficiently preparing phenanthridone and derivatives thereof without metal participation
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The invention discloses a method for efficiently preparing phenanthridone and derivatives without metal participation. The preparation method comprises the step of carrying out cyclization reaction on a compound shown in a formula II under the catalysis of methyl trifluoromethanesulfonate to obtain a phenanthridone compound shown in a formula I. According to the invention, the phenanthridone compound is generated in one step by catalyzing the cyclization reaction of the o-aryl phenyl isocyanate through the trifluoromethanesulfonate, and a practical method is provided for synthesizing the substituted phenanthridone derivative with biological activity. The method is free of using any metal reagent, environmentally friendly, easy to operate, high in yield and simple and convenient in post-treatment. In addition, the substrate obtained by the method is high in designability, a compound with the required structurecan be designed and synthesized according to actual needs, and the practicability is high.
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Paragraph 0042-0048
(2021/06/26)
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- Application of phenanthridine compounds to pesticides
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The invention relates to an application of phenanthridine compounds shown in general formula (1) to pesticides. Part of the compounds is used as a plant virus agent and can well inhibit the tobacco mosaic virus; when used as a bactericide, the compounds have good inhibitory activity on tomato early blight, wheat scab, potato late blight, phytophthora capsici, rape sclerotinia rot, cucumber gray mould, rice sheath blight disease, cucumber fusarium wilt, cercospora brown spot of peanut, apple ring rot, wheat sharp eyespot, corn southern leaf blight, watermelon anthracnose and rice bakanae disease; when used as an insecticide, the compounds have poisonous activity on armyworms, mosquito larvae, cotton bollworms, ostrinia nubilalis, aphids, adult mites and plutella xylostella. In the formula,when molecular nitrogen is not imine, R can represent hydrogen atoms, methyl, acetyl and benzoyl; R and R represent a hydrogen atom or an oxygen atom simultaneously; R and R can represent hydroxyl, acetoxyl, methoxyl, methyleneoxy, a fluorine atom and the hydrogen atom; R is a bromine atom or the fluorine atom; R is the hydrogen atom or vinyl. When nitrogen is imine, R doesnot represent any group; one of R and R does not represent any group, and the other can represent the hydrogen atom, methoxyl, ethyoxyl, benzyloxy and a chlorine atom; R, R, R and Rrepresent the hydrogen atom.
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Paragraph 0020; 0025; 0026
(2019/10/01)
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- Is Fe-catalyzed ortho C-H Arylation of Benzamides Sensitive to Steric Hindrance and Directing Group?
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The previously reported Fe-catalyzed ortho C-H arylation of benzamides relied on bi- or tridentate amide groups and specific iron ligands and was sensitive to steric hindrance. By using new mixed titanates, our present protocol accommodates various weakly coordinating benzamides and tolerates high steric hindrance and sensitive functional groups only under the catalysis of FeCl3 and TMEDA. A wide range of privileged condensed ring compounds can thus be facilely accessed.
- Wei, Yi-Ming,Wang, Meng-Fei,Duan, Xin-Fang
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supporting information
p. 6471 - 6475
(2019/08/26)
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- Phenanthridone derivatives and synthesis method and antitumor application thereof
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The invention provides novel phenanthridone derivatives and a synthesis method and an antitumor application thereof, and belongs to the technical field of medicine. The provided compounds have been subjected to antitumor activity evaluation to prove that
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Paragraph 0114; 0115; 0116
(2019/01/08)
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- Synthetic method for phenanthridone compound
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The invention relates to a synthetic method for a phenanthridone compound. The method comprises the following steps: subjecting benzamide with a guiding group and a benzyne precursor to carbon-hydrogen bond and nitrogen-hydrogen bond activation and cyclization under the co-action of a catalyst, an inorganic base, an additive, a solvent and oxygen so as to produce the core skeleton of the phenanthridone compound; and then removing the guiding group so as to synthesize the phenanthridone compound. Compared with the prior art, the invention has the following advantages: the cheap, easily available and environment-friendly copper catalyst is used, and rare metal catalysts like ruthenium, rhodium and palladium are not used in the reaction; a substrate has diversity; reaction conditions are mild; and the method has good repeatability. The method provided by the invention can synthesize natural phenanthridone products like Phenaglydon and Crinasiadine, provides a new idea for synthesis of phenanthridone compounds and natural amaryllidaceae alkaloid products, and has good application prospects.
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Paragraph 0112; 0114; 0117
(2018/09/08)
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- Facile Synthesis of Phenanthridinone Alkaloids via Suzuki–Miyaura Cross-coupling
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Phenanthridinone alkaloids crinasiadine 1 and N-alkylcrinasiadines 6, 7, 8, 9, 10 have been synthesized based on palladium-catalyzed tandem C–C and C–N bond formation starting from 2-aminophenylboronic acid and 2-bromobenzoate in short steps. Related alka
- Kuwata, Yoshiyuki,Sonoda, Motohiro,Tanimori, Shinji
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p. 1645 - 1651
(2017/03/27)
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- Copper-Catalyzed Selective ortho-C-H/N-H Annulation of Benzamides with Arynes: Synthesis of Phenanthridinone Alkaloids
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An efficient and convenient copper-catalyzed method has been developed to achieve direct ortho-C-H/N-H annulation to synthesize phenanthridinones with arynes. This method highlights an emerging strategy to transform inert C-H bonds into versatile functional groups in organic synthesis and provides a new way to synthesize phenanthridinone alkaloids efficiently.
- Zhang, Ting-Yu,Lin, Jun-Bing,Li, Quan-Zhe,Kang, Jun-Chen,Pan, Jin-Long,Hou, Si-Hua,Chen, Chao,Zhang, Shu-Yu
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supporting information
p. 1764 - 1767
(2017/04/11)
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- Synthesis of phenanthridine skeletal Amaryllidaceae alkaloids
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Strategies for the synthesis of Amaryllidaceae alkaloids, including crinasiadine, trisphaeridine, bicolorine, N-methylcrinasiadine, 5,6-dihydrobicolorine, galanthindole, lycosinine A and lycosinine B were reported. Investigation of optionally synthetic routes to approach bicolorine, 5,6-dihydrobicolorine, trisphaeridine and N-methylcrinasiadine were demonstrated as well. In addition, three structurally related alkaloids galanthindole, lycosinine A and lycosinine B were concisely prepared by using Suzuki coupling reaction as the key step.
- Fan-Chiang, Tai-Ting,Wang, Hung-Kai,Hsieh, Jen-Chieh
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p. 5640 - 5645
(2016/08/17)
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- Palladium-catalyzed oxidative insertion of carbon monoxide to N -sulfonyl-2-aminobiaryls through C-H bond activation: Access to bioactive phenanthridinone derivatives in one pot
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Palladium-catalyzed oxidative carbonylation of N-sulfonyl-2-aminobiaryls through C-H bond activation and C-C, C-N bond formation under TFA-free and milder conditions has been developed. The reaction tolerates a variety of substrates and provides biologically important phenanthridinone derivatives in yields up to 94%.
- Rajeshkumar, Venkatachalam,Lee, Tai-Hua,Chuang, Shih-Ching
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p. 1468 - 1471
(2013/06/26)
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- Synthesis of quinolines, 2-quinolones, phenanthridines, and 6(5H)-phenanthridinones via palladium[0]-mediated Ullmann cross-coupling of 1-bromo-2-nitroarenes with β-halo-enals, -enones, or -esters
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Palladium[0]-mediated Ullmann cross-coupling of 1-bromo-2-nitrobenzene (1 R = H) and its derivatives with a range of β-halo-enals, -enones, or -esters readily affords the corresponding β-aryl derivatives, which are converted into the corresponding quinolines, 2-quinolones, phenanthridines, or 6(5H)-phenanthridinones on reaction with dihydrogen in the presence of Pd on C or with TiCl3 in aqueous acetone.
- Banwell, Martin G.,Lupton, David W.,Ma, Xinghua,Renner, Jens,Sydnes, Magne O.
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p. 2741 - 2744
(2007/10/03)
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- Convergent Routes to the Dioxolophenanthridin-6(5H)-one and 2,3,4,4a-Tetrahydrodioxolophenanthridin-6(5H)-one Nuclei. Application to Syntheses of the Amaryllidaceae Alkaloids Crinasiadine, N-Methylcrinasiadine and Trisphaeridine
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Convergent routes to the title nuclei, (1) and (6), have been developed.Thus, Suzuki coupling of boronic acid (8) with aryl bromide (9) gave the biarylylcarbamate (7) which, on treatment with phosphorus oxychloride (POCl3), underwent Bischler-Napieralski
- Banwell, Martin G.,Cowden, Cameron J.
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p. 2235 - 2254
(2007/10/02)
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