5956-87-6Relevant academic research and scientific papers
Production process of evodiamine and method for recycling solvent in production
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Paragraph 0018; 0042; 0045; 0052; 0055, (2021/02/24)
The invention relates to the field of organic synthesis, in particular to a production process of evodiamine and a method for recycling a solvent in production. According to the method, tryptamine isadopted as a raw material, evodiamine is obtained through formylation, cyclization and condensation ring closing, phosgene and ethyl chloroformate are prevented from being used in the whole process, the safety risk in the production process is reduced, and the reaction steps are greatly simplified. Meanwhile, a solvent application process in production is realized, so that the production cost is greatly reduced, and the method has an industrial popularization value.
Design, synthesis and bioactivity study of evodiamine derivatives as multifunctional agents for the treatment of hepatocellular carcinoma
Fan, Xiaohong,Deng, Jiedan,Shi, Tao,Wen, Huaixiu,Li, Junfang,Liang, Ziyi,Lei, Fang,Liu, Dan,Zhang, Honghua,Liang, Yan,Hao, Xiangyong,Wang, Zhen
, (2021/07/14)
Topoisomerase has been found extremely high level of expression in hepatocellular carcinoma (HCC) and proven to promote the proliferation and survival of HCC. Cancer-associated fibroblasts (CAFs) as a kind of key reactive stromal cell that abundantly present in the microenvironment of HCC, could enhance the metastatic ability and drug resistance of HCC. Therefore, developing new drugs that address the above conundrums would be of the upmost significant in the fight against HCC. Evodiamine, as a multi-target natural product, has been found to exert various biological activities such as anti-cancer and anti-hepatic fibrosis via blocking topoisomerase, NF-κB, TGF-β/HGF, and Smad2/3. Inspired by these facts, 15 evodiamine derivatives were designed and synthesized for HCC treatment by simultaneously targeting Topo I and CAFs. Most of them displayed preferable anti-HCC activities on three HCC cell lines and low cytotoxicity on one normal hepatic cell. In particular, compound 8 showed the best inhibitory effect on HCC cell lines and a good inhibition on Topo I in vitro. Meanwhile, it also induced obvious G2/M arrest and apoptosis, and significantly decreased the migration and invasion capacity of HCC cells. In addition, compound 8 down-regulated the expression of type I collagen in the activated HSC-T6 cells, and induced the apoptosis of activated HSC-T6 cells. In vivo studies demonstrated that compound 8 markedly decreased the volume and weight of tumor (TGI = 40.53%). In vitro and in vivo studies showed that its effects were superior to those of evodiamine. This preliminary attempt may provide a promising strategy for developing anti-HCC lead compounds taking effect through simultaneous inhibition on Topo I and CAFs.
Palladium-Catalyzed Carbonylative Difunctionalization of C=N Bond of Azaarenes or Imines to Quinazolinones
Zhou, Xibing,Ding, Yongzheng,Huang, Hanmin
, p. 1678 - 1682 (2020/05/05)
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.
Discovery of Evodiamine Derivatives as Highly Selective PDE5 Inhibitors Targeting a Unique Allosteric Pocket
Zhang, Tianhua,Lai, Zengwei,Yuan, Suying,Huang, Yi-You,Dong, Guoqiang,Sheng, Chunquan,Ke, Hengming,Luo, Hai-Bin
, p. 9828 - 9837 (2020/10/19)
Clinical use of phosphodiesterase-5 (PDE5) inhibitors is limited by several side effects due to weak isoform selectivity. Herein, a unique allosteric pocket of PDE5 is identified by molecular modeling and structural biology, which enables the discovery of highly selective PDE5 inhibitors from natural product evodiamine (EVO). The crystal structure of PDE5 with bound EVO derivative (S)-7e revealed that binding of (S)-7e to the novel allosteric pocket induced dramatic conformation changes in the H-loop with a maximum 24 ? movement of their Cα atoms. This movement directly blocks the binding of substrate/inhibitors to the PDE5 active site, which is different from all traditional PDE5 inhibitors such as sildenafil, tadalafil, and vardenafil. These derivatives showed >570-fold selectivity over PDE6C and PDE11A and achieved potent efficacy for the effective treatment of pulmonary hypertension in vivo.
Palladium-Catalyzed Multistep Tandem Carbonylation/N-Dealkylation/Carbonylation Reaction: Access to Isatoic Anhydrides
Wang, Shoucai,Li, Xuan,Zang, Jiawang,Liu, Meichen,Zhang, Siyu,Jiang, Guangbin,Ji, Fanghua
, p. 2672 - 2679 (2020/02/04)
A novel and efficient synthesis of isatoic anhydride derivatives was developed via palladium-catalyzed multistep tandem carbonylation/N-dealkylation/carbonylation reaction with alkyl as the leaving group and tertiary anilines as nitrogen nucleophiles. This approach features good functional group compatibility and readily available starting materials. Furthermore, it provided a convenient approach for the synthesis of biologically and medicinally useful evodiamine.
A concise synthesis and biological study of evodiamine and its analogues
Deng, Jie-Dan,Lei, Shuai,Jiang, Yi,Zhang, Hong-Hua,Hu, Xiao-Ling,Wen, Huai-Xiu,Tan, Wen,Wang, Zhen
, p. 3089 - 3092 (2019/03/29)
Efficient access to evodiamine and its analogues is presented via Lewis acid catalysis. In this reaction, three chemical bonds and two heterocyclic-fused rings are constructed in one step. The reaction shows good functional group tolerance and atom economy, and various heteroatom-containing evodiamine analogues are obtained in moderate to excellent yields even on a gram scale. An anti-tumor study in vitro demonstrates compound 2b possesses potent efficacy against hepatoma cell line (IC50 = 5.7 μM).
One-Pot Total Synthesis of Evodiamine and Its Analogues through a Continuous Biscyclization Reaction
Wang, Zi-Xuan,Xiang, Jia-Chen,Wang, Miao,Ma, Jin-Tian,Wu, Yan-Dong,Wu, An-Xin
, p. 6380 - 6383 (2018/10/20)
The one-pot total synthesis of evodiamine and its analogues is achieved using a three-component reaction. Through continuous biscyclization, various readily available substrates with good functional group tolerance were easily incorporated into biologically active quinazolinocarboline backbones. The use of triethoxymethane as a cosolvent was crucial for this quick and straightforward transformation.
A method for utilizing the carbonylation reaction three-step synthetic evodiamine method (by machine translation)
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, (2018/04/02)
The invention discloses a three-step synthesis of carbonylation reaction evodiamine method. First of all in order to N, N - dimethyl aniline as the raw materials of reaction by oxidative carbonylation reaction to obtain N - methyl isatin anhydride, by ammonolysis reaction to obtain N - (2 - indole ethyl) - 2 - (methylamino) benzamide, finally through the cyclization reaction of the three-step synthesis tetradium alkalizing compound. The method of the invention the synthesis of novel means, reaction and is simple, the synthesis step is succinct, mild reaction conditions, the process is simple, consistent with the requirements of the development of green chemistry, and utilize the carbonylation reaction has succeeded in synthesizing evodiamine. (by machine translation)
Silver Nitrate-Catalyzed Isocyanide Insertion/Lactamization Sequence to Imidazolones and Quinazolin-4-ones: Development and Application in Natural Product Synthesis
Clemenceau, Antonin,Wang, Qian,Zhu, Jieping
supporting information, p. 4872 - 4875 (2017/09/23)
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.
Investigation into the stability and reactivity of the pentacyclic alkaloid dehydroevodiamine and the benz-analog thereof
Wehle, Sarah,Espargaró, Alba,Sabaté, Raimon,Decker, Michael
supporting information, p. 2535 - 2543 (2016/04/26)
Limited synthetic approaches to obtain the biologically active alkaloid dehydroevodiamine (DHED) are known to date. Undesired demethylation in the most widely applied route was found to be a hampering side reaction for the benz-DHED derivative leading to a quinazolinone, which represents a benz-rutaecarpine derivative. For rutaecarpine, a related plant alkaloid, many different synthetic approaches have been described. Alternative reaction procedures to obtain DHED such as methylation of rutaecarpine and oxidation of evodiamine were investigated to make DHED more easily accessible and the latter method proved to be the most successful one. Furthermore, the remarkable equilibrium between the ring closed quinazolinium and the ring open form of the compounds was systematically investigated by UV-vis measurements. The ring open form and the quinazolinium salt, form the same species when incubated in buffer solution for 24 h. A better soluble form, i.e., 'hydroxyevodiamine', seems to represent the biologically active form that has not yet been described.
