Artemisinin derivatives containing piperazine ring and fluorine element, and preparation method and application of artemisinin derivatives
Artemisinin derivatives and derivative technology, applied in the field of artemisinin derivatives and their preparation
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Embodiment 1
[0080] A preparation method of an artemisinin derivative containing a piperazine ring and a fluorine element, the process of which is shown in formula (1-1):
[0081]
[0082] R 3 : a=p-CH 3 , b=p-F, c=m-F, d=o-F, e=p-CF 3 , f=m-CF 3 , g=m-OCF 3 , h=p-SCF 3 ;
[0083] R 4 : a=p-F, b=m-F, c=o-F, d=p-CF 3 , e=p-OCF 3 .
[0084] Include the following steps:
[0085] (1) Preparation of Compound 9
[0086] Artemisinin (5 g, 17.73 mmol, compound 8) was dissolved in anhydrous methanol (120 mL), and cooled to 0-5 °C in an ice bath. To this solution was added sodium borohydride (3equ, 2.02g) in portions over 30 minutes. The mixture was stirred at 0-5°C for about 30 minutes and neutralized to pH 7.0 with acetic acid. The reaction solution was concentrated to remove most of the methanol, diluted with cold water (60 mL), and stirred at room temperature for 15 minutes. The precipitate was collected, washed with water (20 mL*3), and dried to obtain 4.51 g of a white solid p...
Embodiment 2
[0142] A preparation method of an artemisinin derivative containing a piperazine ring and a fluorine element, the process of which is shown in formula (1-4):
[0143]
[0144] R 5 : R 7 : a=p-CH 3 , b=p-F, c=m-F, d=o-F, e=p-CF 3 , f=m-CF 3 , g=m-OCF 3 , h=p-SCF 3 ;
[0145] R 6 : R 8 : a=p-F, b=m-F, c=o-F, d=m-CF 3 , e=p-CF 3 , f=p-SCF 3 , g=m-SCF 3 , h=p-OCF 3 .
[0146] Concrete preparation process comprises the following steps:
[0147] (1) Preparation of Compound 14
[0148] Boron trifluoride-diethyl ether (3 mL) was added to a stirred solution of 9 (2.56 g, 9 mmol) at 0 °C, and the mixture was slowly warmed to room temperature and stirred for 2 h. Then the reaction solution was washed with saturated NaHCO 3 The aqueous solution was quenched with anhydrous Na 2 SO 4 dry. Filtration and concentration of the filtrate gave a residue which was purified on chromatography to give the product as a white solid (2.15 g, 90%).
[0149] (2) Preparation of ...
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[0194] 1. Cell culture
[0195] The present invention selects seven cancer cell lines and human normal liver cell line LO2, the seven cancer cell lines are respectively MCF-7 (breast cancer cells), A549 (human lung adenocarcinoma cells), PC12 (pheochromocytoma cells) , SH-SY5Y (human liver cancer cells), U87MG (human glioblastoma cells), U118MG (human brain astroglioma cells) and HCT116 (colorectal cancer cells), these seven cell lines were purchased from Shanghai Biopal Ltd. (Shanghai, China).
[0196] MCF-7, A549, HCT116, PC12, U87MG and U118MG were cultured in DMEM medium supplemented with 10% FBS, 1% penicillin and streptomycin. SH-SY5Y cells were maintained in DMEM / F12 medium supplemented with 10% FBS, 1% penicillin and streptomycin. All seven cell lines were incubated at 37°C, 5% CO 2 cultivated in a moist atmosphere.
[0197] 2. Determination of cell viability
[0198] (1) Cell viability was assessed by MTT assay. Each compound was dissolved in DMSO and diluted wi...
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