- Cytotoxic hybrids between the aromatic alkaloids bauerine C and rutaecarpine
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Two hybrids between the alkaloids bauerine C and rutaecarpine were prepared. Screening for cytotoxic activity revealed that introduction of two chlorine substituents to the quinazolinocarboline core of rutaecarpine strongly enhances cytotoxic activity, wh
- Huber, Kilian,Bracher, Franz
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Read Online
- Sequential sonagashira and larock indole synthesis reactions in a general strategy to prepare biologically active β-carboline-containing alkaloids
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A general synthetic approach to β-carboline-containing alkaloids was developed. Two consecutive palladium-mediated processes, a Sonagashira coupling and a Larock indole annulation reaction, are central to the method. The scope of the approach was investigated and found to be amenable for constructing a variety of biologically significant natural products and also for preparing substituted analogues for optimization and analysis of their biological properties.
- Pan, Xiaohong,Bannister, Thomas D.
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Read Online
- Synthesis of 1-Thio-Substituted Isoquinoline Derivatives by Tandem Cyclization of Isothiocyanates
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A copper-catalyzed tandem arylation-cyclization process to access 1-(arylthio)isoquinolines from isothiocyanates and diaryliodonium salts is described. It is the first general method to construct the potentially useful 1-(arylthio)isoquinoline derivatives. Moreover, 1-(methylthio)isoquinoline derivatives were also achieved successfully with MeOTf instead of diaryliodonium salts under metal-free conditions. Mechanistic studies reveal that these two processes proceed in different routes. This method has been successfully applied to the synthesis of quinazolinone alkaloid rutaecarpine.
- Wen, Li-Rong,Dou, Qian,Wang, Yuan-Chao,Zhang, Jin-Wei,Guo, Wei-Si,Li, Ming
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Read Online
- Preparation method of 2-trifluoromethyl substituted quinazolinone compound and application of 2-trifluoromethyl substituted quinazolinone compound in synthesis of pharmaceutical molecules
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The invention discloses a preparation method of a 2-trifluoromethyl substituted quinazolinone compound. The preparation method comprises the following steps: adding a palladium catalyst, a ligand, a carbon monoxide substitute, an additive, trifluoroethylimido acyl chloride and amine into an organic solvent, reacting at 110 DEG C for 16-30 hours, and after the reaction is completed, carrying out post-treatment to obtain the 2-trifluoromethyl substituted quinazolinone compound. The preparation method has the advantages of simple operation, cheap and easily available initial raw materials, high reaction efficiency, good substrate compatibility, synthesis of trifluoromethyl quinazolinone compounds substituted by different groups through substrate design, convenient operation, and broadening of the practicality of the method. The method is also successfully applied to the high-yield synthesis of the drug molecule Rutaecarpine.
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Paragraph 0042; 0045
(2021/07/01)
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- Metal-Free Annulation of 2-Nitrobenzyl Alcohols and Tetrahydroisoquinolines toward the Divergent Synthesis of Quinazolinones and Quinazolinethiones
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A simple metal-free method for the synthesis of quinazolinones from commercially available 2-nitrobenzyl alcohols and tetrahydroisoquinolines is developed. The reaction conditions were tolerant of an array of functionalities such as halogen, tertiary amine, protected alcohol, and ester groups. Under nearly identical conditions, quinazolinethiones were obtained in the presence of elemental sulfur and suitable mediators.
- Le, Nhan T. H.,Ly, Duc,Nguyen, Khang X.,Nguyen, Thao T.,Nguyen, Tung T.,Nguyen, Vy P. T.,Pham, Phuc H.,Phan, Nam T. S.,Tran, Cam T. H.
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- Copper-catalyzed synthesis of pyrido-fused quinazolinones from 2-aminoarylmethanols and isoquinolines or tetrahydroisoquinolines
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Pyrido-fused quinazolinones were synthesizedviacopper-catalyzed cascade C(sp2)-H amination and annulation of 2-aminoarylmethanols with isoquinolines or pyridines. The transformation proceeded readily in the presence of a commercially available CuCl2catalyst with molecular oxygen as a green oxidant. Moreover, the dehydrogenative cross-coupling of 2-aminoarylmethanols with tetrahydroisoquinolines was explored, in which CuBr exhibited higher catalytic activity than CuCl2. Broad substrate scope with good tolerance of functionalities was observed under the optimized reaction conditions. The bioactive naturally occurring alkaloid rutaecarpine could be obtained by this strategy. The remarkable feature of this protocol is that complicated heterocyclic structures are readily achieved in a single synthetic step from easily accessible reactants and catalysts. This pathway to pyrido-fused quinazolinones would be complementary to existing protocols.
- Ly, Duc,Nguyen, Duyen K.,Nguyen, Khang X.,Nguyen, Khoa D.,Nguyen, Thao T.,Nguyen, Tung T.,Pham, Phuc H.,Phan, Nam T. S.
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supporting information
p. 4726 - 4732
(2021/06/09)
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- Visible-Light-Mediated Synthesis of Rutaecarpine Alkaloids through C-N Cross-Coupling Reaction
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A visible-light-initiated cross-dehydrogenative-coupling amination is described, featuring metal- and photocatalyst-free, at room temperature, and using air as an oxidant. The reaction provides a facile approach for the synthesis of rutaecarpine and its derivatives. The substrates with electron-withdrawing groups give higher yields than those with electron-donating groups, but the substituent position has a negligible influence on the yield. Using binaphthyl-diyl hydrogen phosphate and dibenzyl phosphate as catalysts both deliver satisfying yields. This straightforward light-driven strategy might be applicable to the synthesis of quinazolinone derivatives.
- Chen, Dong,Li, Shiqing,Wang, Jinhua,Gou, Tiantian,Zhang, Linfeng,Wang, Guixia,Kong, Xiangfei
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p. 987 - 992
(2021/04/21)
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- Novel PDE5 inhibitors derived from rutaecarpine for the treatment of Alzheimer's disease
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A series of novel rutaecarpine derivatives were synthesized and subjected to pharmacological evaluation as PDE5 inhibitors. The structure–activity relationships were discussed and their binding conformation and simultaneous interaction mode were further clarified by the molecular docking studies. Among the 25 analogues, compound 8i exhibited most potent PDE5 inhibition with IC50 values about 0.086 μM. Moreover, it also produced good effects against scopolamine-induced cognitive impairment in vivo. These results might bring significant instruction for further development of potential PDE5 inhibitors derived from rutaecarpine as a good candidate drug for the treatment of Alzheimer's disease.
- Dong, Yan-Hua,Huang, Xian-Feng,Ke, Heng-Ming,Song, Guo-Qiang,Wang, Jin-Hui,Xu, De-Feng
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- Redox Condensations of o-Nitrobenzaldehydes with Amines under Mild Conditions: Total Synthesis of the Vasicinone Family
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A total synthesis of the vasicinone family of natural products from bulk chemicals was developed. Reductive condensation of o-nitrobenzaldehydes with amines utilizing iron pentacarbonyl as a reducing agent followed by subsequent oxidation leads to a great variety of polycyclic nitrogen-containing heterocycles under mild conditions. Enantiomerically pure vasicinone, rutaecarpine, isaindigotone, and luotonin were synthesized from readily available starting materials like hydroxyproline, nitrobenzaldehyde, pyrrolidine, and piperidine in two to four operational steps without chromatography. The antifungal activity of all products was tested.
- Afanasyev, Oleg I.,Podyacheva, Evgeniya,Rudenko, Alexander,Tsygankov, Alexey A.,Makarova, Maria,Chusov, Denis
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p. 9347 - 9360
(2020/08/14)
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- Electrosynthesis of polycyclic quinazolinones and rutaecarpine from isatoic anhydrides and cyclic amines
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A direct decarboxylative cyclization between readily available isatoic anhydrides and cyclic amines was established to construct polycyclic fused quinazolinones employing electrochemical methods. This procedure was performed in an undivided cell without the use of a transition-metal-catalyst and external oxidant. A broad scope of polycyclic fused quinazolinones were obtained in moderate to good yields. Additionally, rutaecarpine was also prepared through our method in one step in good yield. This journal is
- Chen, Xingyu,Lu, Sixian,Sun, Peng,Zhang, Xing
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p. 44382 - 44386
(2020/12/25)
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- TBHP-Mediated Oxidative Decarboxylative Cyclization in Water: Direct and Sustainable Access to Anti-malarial Polycyclic Fused Quinazolinones and Rutaecarpine
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Polycyclic fused quinazolinones with anti-malarial activity were synthesized through tert-butyl hydroperoxide (TBHP)-mediated oxidative decarboxylative cyclization between commercially available isatins and cyclic amines in one step. The reaction proceeds smoothly in water without additional transition-metal catalyst, acid and base. The newly synthesized products were evaluated to exhibit moderate to good anti-malarial activity against chloroquine drug-sensitive Plasmodium falciparum 3D7 strain. Additionally, this method also provides direct approach to Rutaecarpine in good yield.
- Chen, Xingyu,Xia, Fei,Zhao, Yifan,Ma, Ji,Ma, Yue,Zhang, Dong,Yang, Lan,Sun, Peng
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supporting information
p. 1239 - 1244
(2020/07/27)
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- Palladium-Catalyzed Carbonylative Difunctionalization of C=N Bond of Azaarenes or Imines to Quinazolinones
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Supporting information for this article is given via a link at the end of the document. By intercepting the acylpalladium species with C=N bond of azaarenes or imines other than free amines or alcohols, the difunctionalization of C=N bond was established via palladium-catalyzed carbonylation/nucleophilic addition sequence. This method is compatible with a diverse range of azaarenes and imines and allows for the efficient synthesis of a wide range of quinazolinones and derivatives. The synthetic utility has been demonstrated by one-step synthesis of evodiamine and its analogue with inexpensive starting materials.
- Zhou, Xibing,Ding, Yongzheng,Huang, Hanmin
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p. 1678 - 1682
(2020/05/05)
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- Rutaecarpine-NO donor conjugates and application thereof
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The invention discloses rutaecarpine-NO donor conjugates with chemical structural formulas shown as formula I, formula II and formula III, and application of the rutaecarpine-NO donor conjugates in preparation of drugs promoting calcitonin gene-related peptide (CGRP) release and in preparation of drugs treating hypertension and the like.
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Paragraph 0026; 0033; 0036; 0040
(2019/02/13)
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- Copper-Catalyzed Intramolecular α-C-H Amination via Ring-Opening Cyclization Strategy to Quinazolin-4-ones: Development and Application in Rutaecarpine Synthesis
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A copper-catalyzed intramolecular α-C-H amination has been developed for the synthesis of quinazolin-4(3 H)-one derivatives from commercially available isatoic anhydride and primary and secondary benzylamines via ring-opening cyclization (ROC). This method shows good functional group tolerance and allows access to a range of 2-aryl, 2-alkyl, and spiroquinazolinone derivatives. However, 2-methylquinazolin-4(3 H)-one was synthesized from 2-amino- N -isopropylbenzamide by C-C bond cleavage, and N -benzyl-2-(methylamino)benzamide afforded 1-methyl-2-phenylquinazolin-4(1 H)-one along with 2-phenylquinazolin-4(3 H)-one by N-C bond cleavage for aromatization. It is the first general method to construct the potentially useful 2-methylquinazolin-4(3 H)-one by copper-catalyzed intramolecular C-H amination. Also this ROC strategy has been successfully applied to the synthesis of quinazolinone alkaloid rutaecarpine.
- Biswal, Sonali,Chada, Harika,Patel, Srilaxmi M.,Sharada, Duddu S.,Sharma, Sonika
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p. 3160 - 3170
(2019/08/07)
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- Light-Driven Intramolecular C?N Cross-Coupling via a Long-Lived Photoactive Photoisomer Complex
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Reported herein is a visible-light-driven intramolecular C?N cross-coupling reaction under mild reaction conditions (metal- and photocatalyst-free, at room temperature) via a long-lived photoactive photoisomer complex. This strategy was used to rapidly prepare the N-substituted polycyclic quinazolinone derivatives with a broad substrate scope (>50 examples) and further exploited to synthesize the natural products tryptanthrin, rutaecarpine, and their analogues. The success of gram-scale synthesis and solar-driven transformation, as well as promising tumor-suppressing biological activity, proves the potential of this strategy for practical applications. Mechanistic investigations, including control experiments, DFT calculations, UV-vis spectroscopy, EPR, and X-ray single-crystal structure of the key intermediate, provides insight into the mechanism.
- Jing, Dong,Lu, Cong,Chen, Zhuo,Jin, Songyang,Xie, Lijuan,Meng, Ziyi,Su, Zhishan,Zheng, Ke
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p. 14666 - 14672
(2019/09/06)
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- Catalyst-free cyclization of anthranils and cyclic amines: One-step synthesis of rutaecarpine
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An efficient synthesis of a variety of quinazolinone derivatives via a direct cyclization reaction between commercially available anthranils and cyclic amines is described. The developed transformation proceeds with the merits of high step- and atom-efficiency, a broad substrate scope, and good to excellent yields, without additional catalysts, and offers a practical way for the preparation of rutaecarpine and its derivatives with structural diversity.
- Li, Jian,Wang, Zheng-Bing,Xu, Yue,Lu, Xue-Chen,Zhu, Shang-Rong,Liu, Li
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p. 12072 - 12075
(2019/10/14)
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- Method for preparing rutaecarpin derivative
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The invention discloses a synthesis method of rutaecarpin and derivatives thereof and relates to the field of organic chemicals and medicines. A benzoisooxazole derivative and 2,3,4,9-tetrahydro-1H pyridine[3,4-b] indole are adopted as raw materials, no catalyst is used, methylbenzene is adopted as a solvent, and a reaction is performed under a heating condition so as to obtain a series of rutaecarpin derivatives. By adopting the method disclosed by the invention, the rutaecarpin derivatives can be prepared through one hour of the reaction under a heating and stirring condition, and the yieldis 52-78%. The reaction has the advantages that without metal catalysis, a series of the rutaecarpin derivatives can be prepared from simple and easily obtained raw materials through a one-step reaction, and an efficient, simple and convenient novel synthesis method is provided for synthesizing the rutaecarpin derivatives.
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Paragraph 0016-0017
(2019/12/25)
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- Dual-targeting Rutaecarpine-NO donor hybrids as novel anti-hypertensive agents by promoting release of CGRP
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CGRP, known as the most potent vasodilator substance, plays an important role in hypertension initiation and development. TRPV1 and TRPA1 are critical in promoting the synthesis and release of CGRP, thereby regulating the cardiovascular tone. Rutaecarpine exhibits potent vasodilator and hypertensive effects by stimulating CGRP synthesis and release via activation of TRPV1. And NO has been shown to react with H2S in vivo to form HNO, thereby activating HNO-TRPA1-CGRP pathway. Inspired by combination therapy, 11 rutaecarpine-furoxan hybrids were designed, synthesized and evaluated. The results demonstrated that most hybrids exerted comparable or improved vasodilator activities. Among which, 13a is the most potent both ex vivo (EC50 = 13.1 nM) and in vivo. Mechanistic studies revealed that the vasodilator and anti-hypertensive effects of the hybrids might involve the promotion of CGRP release via dual activation of TRPV1 and TRPA1. This work suggests that dual-targeted hybrids might be an effective and promising approach to discover and develop novel anti-hypertensive drugs.
- Ma, Jinjin,Chen, Lan,Fan, Jinbao,Cao, Wei,Zeng, Guangyao,Wang, Yajing,Li, Yuanjian,Zhou, Yingjun,Deng, Xu
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p. 146 - 153
(2019/02/27)
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- Synthesis of rutaecarpine alkaloids: Via an electrochemical cross dehydrogenation coupling reaction
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Substrates are directly oxidized at the anode without using any metal catalyst and oxidant to obtain a series of nitrogen heterocyclic compounds, including benzimidazoles and quinolinones. These compounds are highly tolerant to various functional groups and heterocycle-containing substrates. In addition, natural alkaloids, such as rutaecarpine and deoxyvasicinone, can be synthesized by this method.
- Li, Qian-Yu,Cheng, Shi-Yan,Tang, Hai-Tao,Pan, Ying-Ming
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supporting information
p. 5517 - 5520
(2019/10/28)
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- Metal-Free Synthesis of Polycyclic Quinazolinones Enabled by a (NH4)2S2O8-Promoted Intramolecular Oxidative Cyclization
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An efficient metal-free, (NH4)2S2O8 mediated intramolecular oxidative cyclization for the construction of polycyclic heterocycles was disclosed. A series of polycyclic quinazolinone derivatives with good functional group tolerance were obtained in high yields. The natural products tryptanthrin and rutaecarpine, as well as their derivatives, were easily synthesized by this strategy. A preliminary mechanism study suggested the carbon-centered radical was involved in the catalytic cycle.
- Xie, Lijuan,Lu, Cong,Jing, Dong,Ou, Xinrui,Zheng, Ke
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supporting information
p. 3649 - 3653
(2019/06/04)
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- Silver Nitrate-Catalyzed Isocyanide Insertion/Lactamization Sequence to Imidazolones and Quinazolin-4-ones: Development and Application in Natural Product Synthesis
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Silver nitrate-catalyzed reaction of methyl α,α-disubstituted α-isocyanoacetates with primary amines afforded 3,5,5-trisubstituted imidazolones in good to excellent yields. A silver salt-catalyzed insertion of the isocyano group into the N-H bond of the amine followed by in situ lactamization accounted for the reaction outcome. The same transformation between methyl 2-isocyanobenzoate and amines afforded quinazolin-4-ones in excellent yields. The utility of this chemistry was illustrated by the development of concise syntheses of (±)-evodiamine and rutaecarpine.
- Clemenceau, Antonin,Wang, Qian,Zhu, Jieping
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supporting information
p. 4872 - 4875
(2017/09/23)
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- Total Synthesis of Luotonin A and Rutaecarpine from an Aldimine via the Designed Cyclization
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The total synthesis of rutaecarpine (1) and luotonin A (2) is described through controlled cyclization of a common aldimine intermediate 5 derived from ethyl-2-aminocinnamate and quinazolinone-2-carbaldehyde. The cyanide-mediated imino-Stetter reaction of aldimine 5 provided the corresponding indole derivative 3, from which the total synthesis of rutaecarpine (1) was completed via the formation of a 6-membered C-ring. On the other hand, microwave-assisted thermal 6π-electrocyclization of the common intermediate 5, followed by the formation of a 5-membered C′-ring, allowed the completion of the total synthesis of luotonin A (2).
- Kwon, Se Hyun,Seo, Hong-Ahn,Cheon, Cheol-Hong
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supporting information
p. 5280 - 5283
(2016/10/31)
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- Condensation of anthranilic acids with pyridines to furnish pyridoquinazolones via pyridine dearomatization
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The unprecedented carbodiimide-mediated condensation between pyridines and anthranilic acids via pyridine dearomatization at room temperature has been developed to provide a straightforward approach to pyridoquinazolones. The value of this approach has further been demonstrated by its application to one-step, gram-scale syntheses of a series of pyridoquinazolone-based natural products and their analogues from readily available starting materials.
- Yang, Yajun,Zhu, Cuiju,Zhang, Min,Huang, Shijun,Lin, Jingjing,Pan, Xiandao,Su, Weiping
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supporting information
p. 12869 - 12872
(2016/11/06)
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- [Fe(F20TPP)Cl]-catalyzed amination with arylamines and {[Fe(F20TPP)(NAr)](PhI=NAr)}+. Intermediate assessed by high-resolution ESI-MS and DFT calculations
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Amination of C-H bonds catalyzed by transition metal complexes via nitrene/imide insertion is an appealing strategy for C-N bond formation, and the use of iminoiodinanes, or their in situ generated forms from 'PhI-(OAc)2 + primary amides (such as sulfonamides, sulfamates, and carbamates)', as nitrogen sources for the amination reaction has been well documented. In this work, a 'metal catalyst + PhI(OAc)2 + primary arylamines' amination protocol has been developed using [Fe(F20TPP)Cl] (H2F20TPP = meso-tetrakis(pentafluorophenyl)porphyrin) as a catalyst. This catalytic method is applicable for both intra- and intermolecular amination of sp2 and sp3 C-H bonds (> 27 examples), affording the amination products, including natural products such as rutaecarpine, in moderate-to-good yields. ESI-MS analysis and DFT calculations lend support for the involvement of {[Fe(F20TPP)(NC6H4-p-NO2)](PhI=NC6H4-p-NO2)}+. intermediate in the catalysis.
- Liu, Yungen,Chen, Guo-Qiang,Tse, Chun-Wai,Guan, Xianguo,Xu, Zheng-Jiang,Huang, Jie-Sheng,Che, Chi-Ming
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supporting information
p. 100 - 105
(2015/02/19)
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- Glyoxylic acid in the reaction of isatoic anhydride with amines: A rapid synthesis of 3-(un)substituted quinazolin-4(3H)-ones leading to rutaecarpine and evodiamine
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A dual reactant/catalyst role of glyoxylic acid in the reaction of isatoic anhydride with various amines afforded a novel, robust and rapid synthesis of 3-(un)substituted quinazolin-4(3H)-ones. This metal catalyst-free reaction proceeds via an unusual and unexpected cleavage of C-C bond. A shorter and common route to two alkaloids, that is, rutaecarpine and evodiamine is also accomplished.
- Rao, K. Raghavendra,Raghunadh, Akula,Mekala, Ramamohan,Meruva, Suresh Babu,Pratap,Krishna,Kalita, Dipak,Laxminarayana, Eppakayala,Prasad, Bagineni,Pal, Manojit
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supporting information
p. 6004 - 6006
(2014/12/12)
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- A simple heterocyclic fusion reaction and its application for expeditious syntheses of rutaecarpine and its analogs
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In the search for new inhibitors of cholinesterases, a simple heterocyclic fusion reaction of isatoic anhydride 8 and 3,4-dihydroisoquinoline 22 was discovered which involves a spontaneous dehydrogenation upon heating. Applying the reaction, the bioactive natural alkaloid rutaecarpine and several substituted derivatives out of tryptamines and anthranilic acids or isatoic anhydrides, respectively, can be synthesized without tedious chromatographic purification. This provides simple and fast access to larger amounts of compounds with this privileged structure in medicinal chemistry.
- Huang, Guozheng,Roos, Dominika,Stadtmüller, Patricia,Decker, Michael
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supporting information
p. 3607 - 3609
(2014/06/23)
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- Facile access to ring-fused aminals via direct α-amination of secondary amines with o-aminobenzaldehydes: Synthesis of vasicine, deoxyvasicine, deoxyvasicinone, mackinazolinone, and ruteacarpine
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Secondary amines undergo redox-neutral reactions with aminobenzaldehydes under conventional and microwave heating to furnish polycyclic aminals via amine α-amination/N-alkylation. This unique α-functionalization reaction proceeds without the involvement of transition metals or other additives. The resulting aminal products are precursors for various quinazolinone alkaloids and their analogues. Georg Thieme Verlag Stuttgart. New York.
- Richers, Matthew T.,Deb, Indubhusan,Platonova, Alena Yu.,Zhang, Chen,Seidel, Daniel
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p. 1730 - 1748
(2013/07/26)
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- Selective copper(II) acetate and potassium iodide catalyzed oxidation of aminals to dihydroquinazoline and quinazolinone alkaloids
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Copper(II) acetate/acetic acid/O2 and potassium iodide/tert-butylhydroperoxide systems are shown to affect the selective oxidation of ring-fused aminals to dihydroquinazolines and quinazolinones, respectively. These methods enable the facile preparation of a number of quinazoline alkaloid natural products and their analogues.
- Richers, Matthew T.,Zhao, Chenfei,Seidel, Daniel
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supporting information
p. 1194 - 1201
(2013/07/26)
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- Multicomponent assembly processes for the synthesis of diverse yohimbine and corynanthe alkaloid analogues
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A strategy involving a Mannich-type multicomponent assembly process followed by a 1,3-dipolar cycloaddition has been developed for the rapid and efficient construction of parent heterocyclic scaffolds bearing indole and isoxazolidine rings. These key intermediates were then readily elaborated using well-established protocols for refunctionalization and cross-coupling to access a diverse 180-member library of novel pentacyclic and tetracyclic compounds related to the Yohimbine and Corynanthe alkaloids. Several other new multicomponent assembly processes were developed to access dihydro-β- carboline-fused benzodiazepines, pyrimidinediones, and rutaecarpine derivatives.
- Granger, Brett A.,Wang, Zhiqian,Kaneda, Kyosuke,Fang, Zhenglai,Martin, Stephen F.
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supporting information
p. 379 - 386
(2013/07/26)
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- Efficient syntheses of 2,3-disubstituted natural quinazolinones via iridium catalysis
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Natural products sclerotigenin, pegamine, deoxyvasicinone, mackinazolinone, and rutaecarpine were synthesized. Core quinazolinone structures were constructed via Ir catalysis. The Royal Society of Chemistry 2012.
- Fang, Jie,Zhou, Jianguang
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p. 2389 - 2391
(2012/04/11)
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- RUTAECARPINE DERIVATIVES FOR ACTIVATING CYP1A2 IN A SUBJECT
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The teachings provided herein generally relate to compositions comprising rutaecarpine derivatives that activates CYP1A2 through enzyme induction. The uses for such a derivative can include removing caffeine from a subject, improving sleep, treating insomnia, treating caffeine toxicity, treating caffeine addiction and withdrawal symptoms, and the like. Caffeine is just one example of a substrate that can be removed using the derivatives taught herein, and other examples, including theophylline, are provided herein.
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Page/Page column 11-13
(2013/02/27)
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- New topoisomerases inhibitors: Synthesis of rutaecarpine derivatives and their inhibitory activity against topoisomerases
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A series of rutaecarpine derivatives were prepared by employing previously reported methods and their inhibitory activities against topoisomerase I and II were evaluated. Among them, strongly cytotoxic 10-bromorutaecarpine and 3-chlororutaecarpine showed strong inhibitory activities against topo I and II.
- Kim, Seung Ill,Lee, Seung Ho,Lee, Eung-Seok,Lee, Chong-Soon,Jahng, Yurngdong
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experimental part
p. 785 - 789
(2012/08/29)
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- Total synthesis of rutaecarpine and analogues by tandem azido reductive cyclization assisted by microwave irradiation
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The total synthesis of rutaecarpine and several analogues has been developed by using an azido reductive cyclization process starting from substituted azido benzoic acids. The intramolecular azido reductive cyclization step was performed with triphenylphosphine or Ni2B in HCl-MeOH (1 M) using microwave irradiation. This synthetic route is amenable for the generation of a library of quinazolinone compounds. Georg Thieme Verlag Stuttgart - New York.
- Kamal, Ahmed,Reddy, M. Kashi,Reddy, T. Srinivasa,Santos, Leonardo Silva,Shankaraiah, Nagula
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scheme or table
p. 61 - 64
(2011/02/25)
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- Multicomponent assembly strategies for the synthesis of diverse tetrahydroisoquinoline scaffolds
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Several novel multicomponent assembly processes have been developed for the rapid and efficient assembly of various heterocyclic scaffolds bearing a tetrahydroisoquinoline core, each of which allows for facile derivatization to access a diverse array of compounds. This work led to the serendipitous discovery of a new method for the synthesis of a fused quinazolone ring system, which was applied to a one-step total synthesis of the quinazolinocarboline alkaloid rutaecarpine.
- Granger, Brett A.,Kaneda, Kyosuke,Martin, Stephen F.
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supporting information; experimental part
p. 4542 - 4545
(2011/10/09)
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- Bicyclic 1,2,3-triazolium ionic liquids: Synthesis, characterization, and application to rutaecarpine synthesis
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Starting with commercial reagents, bicyclic 1,2,3-triazolium ionic liquids [b-3C-tr][NTf2] (1) and [b-4C-tr][NTf2] (2) were synthesized in four steps with high overall isolated yields of 68% and 76%, respectively. Since the C-5 hydrogen is acidic, under basic condition ionic liquids 1 and 2 were readily methylated with methyl iodide to afford chemically stable ionic liquids 7 and 8 at room temperature (88% and 82%, respectively). Ionic liquid 1 was used as the ionic solvent to demonstrate its usefulness for the synthesis of rutaecarpine, a natural product.
- Tseng, Ming-Chung,Cheng, Hui-Ting,Shen, Meng-Jane,Chu, Yen-Ho
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scheme or table
p. 4434 - 4437
(2011/10/05)
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- Intramolecular N-aza-amidoalkylation in association with Witkop-Winterfeldt oxidation as the key step to synthesize Luotonin-A analogues
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An expedient four-step approach for the synthesis of a short library of original analogues of the Topo-I Luotonin-A inhibitor, substituted at their C8- and N15-positions, was investigated. This consists of Rutaecarpines formation, their Witkop-Winterfeldt oxidation followed ultimately with functional adjustment of the pyrroloquinolone intermediates. In the first step of these investigations, Rutaecarpines including the Topo-I poison Evodiamine were obtained via the new tandem N-acylation/aza-amidoalkylation using a nitrogen atom as an internal nucleophile with or without association with a decarboxylation.
- Pin, Frédéric,Comesse, Sébastien,Da?ch, Adam
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p. 5564 - 5571
(2011/08/09)
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- Synthesis and vasodilator effects of rutaecarpine analogues which might be involved transient receptor potential vanilloid subfamily, member 1 (TRPV1)
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Rutaecarpine is the major alkaloid component of Wu-Chu-Yu, a well known Chinese herbal drug. It has been reported that rutaecarpine causes the vasodilator, hypotensive effects by stimulation of CGRP synthesis and release via activation of TRPV1. In present study, 23 rutaecarpine analogues were designed and synthesized. Then, the vasodilator effects of theses compounds were screened by rat aortic ring experiment. The result showed that the 14-N atom of rutaecarpine might be the key site for the activity. The 5-carbonyl might make lower contribution to the effect. And simple substitute in indole-ring or quinazoline-ring would not enhance the vasodilator effect unless in proper position with proper group. One of these compounds, 10-methylrutaecarpine, exhibited similar effect with rutaecarpine. Further functional experiments showed its vasodilator and hypotensive effect were related to the stimulation of CGRP release via activation of TRPV1. The vasodilator effects of these compounds were evaluated and the structure-activity relationship was elucidated for the first time. The results suggested a new direction of valuable TRPV1 agonist as anti-hypertensive drugs.
- Chen, Zhuo,Hu, Gaoyun,Li, Dai,Chen, Jun,Li, Yuanjian,Zhou, Huayong,Xie, Ye
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experimental part
p. 2351 - 2359
(2009/09/08)
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- A new and facile synthesis of rutaecarpine alkaloids
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Relevant rutaecarpine analogues (1a-d) have been synthesized efficiently from the ring opened β-carboline derivatives (3a-d) as key intermediates. A unique one-pot reductive-cyclization as key reaction furnished the synthesis of rutaecarpine alkaloids in excellent yields. The key intermediates (3a-d) were prepared from tryptamine following acylation, Bischler-Napieralski cyclization, benzoylation, and oxidative cleavage of the exocyclic double bond. This new synthetic approach provides a facile access to rutaecarpine analogues with potent inhibitory effect on platelet aggregation.
- Lee, Chih-Shone,Liu, Cheng-Kuo,Cheng, Yen-Yao,Teng, Che-Ming
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experimental part
p. 1047 - 1056
(2009/10/04)
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- α-amination of nitrogen heterocycles: Ring-fused aminals
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Aromatic aminoaldehydes react with cyclic amines to produce ring-fused aminals under thermal conditions. This process is applied to two-step syntheses of the quinazolinone alkaloids deoxyvasicinone and rutaecarpine. Copyright
- Zhang, Chen,De, Chandra Kanta,Mal, Rudrajit,Seidel, Daniel
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p. 416 - 417
(2008/09/20)
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- One-pot synthesis of simple alkaloids: 2,3-Polymethylene-4(3H)- quinazolinones, luotonin A, tryptanthrin, and rutaecarpine
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One-pot synthesis of various 2,3-polymethylene-4(3H)-quinazolinones from anthranilic acid, corresponding lactam and SOCl2 is described, which can be applicable to the synthesis of simple 4(3H)-quinazolinone-derived alkaloids, such as luotonin A, tryptanthrin, and rutaecarpine.
- Jahng, Katherine Chae,Kim, Seung Ill,Kim, Dong Hyeon,Seo, Chang Seob,Son, Jong-Keun,Lee, Seung Ho,Lee, Eung Seok,Jahng, Yurngdong
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scheme or table
p. 607 - 609
(2009/04/06)
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- One-pot reductive-cyclization as key step for the synthesis of rutaecarpine alkaloids
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The quinazolinocarboline alkaloids including rutaecarpine (1a), euxylophoricine A (1b), and euxylophoricine C (1c) have been synthesized efficiently from the ring opened β-carboline derivative as key intermediate by a one-pot reductive-cyclization reaction. The key intermediate was prepared from tryptamine (6) following Bischler-Napieralski cyclization, benzoylation, and oxidative cleavage of the exocyclic double bond.
- Lee, Chih-Shone,Liu, Cheng-Kuo,Chiang, Yuen-Lin,Cheng, Yen-Yao
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p. 481 - 484
(2008/09/17)
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- Radical reactions with 3H-quinazolin-4-ones: Synthesis of deoxyvasicinone, mackinazolinone, luotonin A, rutaecarpine and tryptanthrin
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Alkyl, aryl, heteroaryl and acyl radicals have been cyclised onto the 2-position of 3H-quinazolin-4-one. The side chains containing the radical precursors were attached to the nitrogen atom in the 3-position. The cyclisations take place by aromatic homolytic substitution hence retain the aromaticity of the 3H-quinazolin-4-one ring. The highest yields were obtained using hexamethylditin to facilitate cyclisation rather than reduction without cyclisation. The alkaloids deoxyvasicinone 2, mackinazolinone 3, tryptanthrin 4, luotonin A 5 and rutaecarpine 8 were synthesised by radical cyclisation onto 3H-quinazolin-4-one. This journal is The Royal Society of Chemistry.
- Bowman, W. Russell,Elsegood, Mark R. J.,Stein, Tobias,Weaver, George W.
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p. 103 - 113
(2008/03/14)
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- Expedious and practical synthesis of the bioactive alkaloids rutaecarpine, euxylophoricine A, deoxyvasicinone and their heterocyclic homologues
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Efficient assembly of pyrimido-β-carbolines 1 and 2, including the bioactive alkaloids rutaecarpine, euxylophoricine A, and deoxyvasicinone (3), is reported from suitable aromatic amino acids 7 or corresponding aromatic amino esters 8 and imino-thioethers 5 or 6 in a one-step sequence in moderate to good yields. The key step of this methodology is based on an intramolecular aza-displacement of a methylthio group followed by spontaneous cyclodehydration. Furthermore, when aromatic amino esters 8 were used instead of amino acids, a tandem amino-methylthio displacement/amino ester cyclization takes place.
- Hamid, Abdulkareem,Elomri, Abdelhakim,Da?ch, Adam
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p. 1777 - 1781
(2007/10/03)
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- Novel inhibitors of acetyl- and butyrylcholinesterase derived from the alkaloids dehydroevodiamine and rutaecarpine
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Derived from the structures of the alkaloids rutaecarpine and dehydroevodiamine (DHED), and the long-known acetylcholinesterase (AChE) inhibitor tacrine, respectively, novel compounds were synthesised, including: 13-methyl-5,8-dihydro-6H-isoquino[1,2-b]quinazolin-13-ium chloride (12), (8Z)-5,6-dihydro-8H-isoquino[1,2-b]quinazolin-8-imine (13), 5,8-dihydro-6H- isoquino[1,2-b]quinazoline (15a), 13-methyl-5,8-dihydro-6H-isoquino[1,2-b] quinazolin-13-ium chloride (16), 5,7,8,13-tetrahydroindolo [2′,3′:3, 4]pyrido[2,1-b]quinazoline (17), and N-(2-phenylethyl)-N-[(12Z)-7,8,9,10- tetrahydroazepino [2,1-b]quinazolin-12(6H)-ylidene]amine (20), respectively. In a first step to evaluate their possible applicability for antiamnesic therapy, the inhibition of AChE and butyrylcholinesterase (BChE) were determined: compounds 13, 15a, 17, and 20 are moderate or strong inhibitors of ChE, the latter two compounds show a 10-fold higher affinity to BChE. Compound 12 is a moderate inhibitor of AChE showing selectivity towards this enzyme. (Chemical presented)
- Decker, Michael
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p. 305 - 313
(2007/10/03)
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- Facile zeolite induced Fischer-indole synthesis: A new approach to bioactive natural product rutaecarpine
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Starting from glutaric anhydride (5) we have demonstrated an elegant six-step practical synthesis of bioactive natural product rutaecarpine (1a) via o-amidoglutaranilic acid formation, esterification, chemoselective ester reduction, intramolecular dehydrative cyclizations, hydrazone formation and zeolite induced Fischer-indole synthesis with 53% overall yield. The conditions employed in the present synthesis are mild, efficient and general.
- Mhaske, Santosh B.,Argade, Narshinha P.
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p. 3417 - 3420
(2007/10/03)
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- Concise synthesis of quinazoline alkaloids, luotonins A and B, and rutaecarpine
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The total synthesis of luotonin A was achieved in excellent yield by using a Pd-assisted biaryl coupling reaction of N-(bromoquinolinyl)methylquinazolinone with Cy3P and KOAc. The successive treatment of luotonin A with NBS and aq. AgNO3 gave luotonin B in good yield. Although the Pd-assisted coupling reaction of N-(2-bromoindolyl)ethylquinazolinone with Cy3P and KOAc yielded rutaecarpine in poor yield, N-acetate under the same reaction conditions yielded the desired rutaecarpine directly in excellent yield. Graphical Abstract.
- Harayama, Takashi,Hori, Akihiro,Serban, Georgeta,Morikami, Yoshiaki,Matsumoto, Takuya,Abe, Hitoshi,Takeuchi, Yasuo
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p. 10645 - 10649
(2007/10/03)
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- A facile total synthesis of rutaecarpine
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The indoloquinazoline alkaloid rutaecarpine has been synthesized efficiently by employing 9,10,11,12-tetrahydro-4H-pyrido[2,1-b]quinazoline-4,9- dione (4) as a key intermediate, which was prepared by adapting a Dieckmann condensation-decarboxylation sequence from quinazolinone diester 6.
- Chavan, Subhash P.,Sivappa
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p. 997 - 999
(2007/10/03)
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- A facile synthesis of simple alkaloids - Synthesis of 2,3-polymethylene-4(3H)-quinazolinones and related alkaloids
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An efficient procedure for preparation of the simple alkaloids, 2,3-polymethylene-4(3H)-quinazolinones, luotonin A, tryptanthrin, and rutaecarpine has been established by the reaction of lactam-HCl salts with POCl3 followed by cyclization with methyl anthranilate.
- Lee, Eung Seok,Park, Jae-Gyu,Jahng, Yurngdong
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p. 1883 - 1886
(2007/10/03)
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- A short synthesis of quinazolinocarboline alkaloids rutaecarpine, hortiacine, euxylophoricine A and euxylophoricine D from methyl N-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)anthranilates
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Reactions of methyl N-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)anthranilates with tryptamine at room temperature produced 2-cyano-3-[2-(indol-3-yl)ethyl]-4(3H)-quinazolinones, which underwent cyclization on heating with TFAA/HCl(g) to afford quinazolinocarboline alkaloids rutaecarpine (1a), hortiacine (1b), euxylophoricine A (1c) and euxylophoricine D (1d) in excellent yields.
- Mohanta, Pramod K.,Kim, Kyongtae
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p. 3993 - 3996
(2007/10/03)
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- A simple synthesis of rutaecarpine
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Indoloquinazoline alkaloid rutaecarpine was efficiently synthesized by employing 9,10,11,12-tetrahydro-4H-pyrido[2,1-b]quinazoline-4,9-dione as a key intermediate, whose 9-carbonyl group was introduced by benzylidene formation, followed by ozonolysis.
- Lee, Seung Ho,Kim, Seung Ill,Park, Jae Gyu,Lee, Eung Seok,Jahng, Yurngdong
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p. 1555 - 1567
(2007/10/03)
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