2-二茂铁基乙醇的合成及其抗肿瘤活性  

Synthesis and anti-tumor activity evaluation of 2-ferrocenylethanol

作　　者：问娟娟 刘斌[1] 赵新红[2] 刘浪浪[2,3] 仝红娟 WEN Juanjuan;LIU Bin;ZHAO Xinhong;LIU Langlang;TONG Hongjuan(Collaborative Innovation Center of Green Manufacturing Technology for Traditional Chinese Medicine in Shaanxi Province,School of Pharmacy,Shaanxi Institute of International Trade&Commerce,Xi'an 712046,Shaanxi,China;School of Petrochemical Engineering,Lanzhou University of Technology,Lanzhou 730050,Gansu,China;Shaanxi Baotashan Paint Co.,Ltd.,Xingping 713100,Shaanxi,China)

机构地区：[1]陕西国际商贸学院医药学院,陕西省中药绿色制造技术协同创新中心,陕西西安712046 [2]兰州理工大学石油化工学院,甘肃兰州730050 [3]陕西宝塔山油漆股份有限公司,陕西兴平713100

出　　处：《精细化工》2020年第11期2320-2324,共5页Fine Chemicals

基　　金：陕西省自然科学基础研究计划(面上)(2018JM7046);陕西省教育厅专项科研计划项目(20JK0513);陕西国际商贸学院校级课题(SMXY201914);陕西国际商贸学院“中药药效物质研究”创新团队建设项目资助(SSY18TD01)。

摘　　要：二茂铁与乙酸酐发生Friedel-Crafts酰基化反应制得了乙酰基二茂铁,接着通过Willgerodt-Kindler反应制得二茂铁乙酸,再经过还原反应得到了目标化合物2-二茂铁基乙醇。考察了反应条件对二茂铁乙酸还原成2-二茂铁基乙醇收率的影响。在还原剂为氢化铝锂、溶剂为四氢呋喃、n(氢化铝锂)∶n(二茂铁乙酸)=8∶1,反应温度为25℃,反应时间为24 h的最佳还原条件下,2-二茂铁基乙醇的收率为82%。体外活性测试结果表明,2-二茂铁基乙醇对人乳腺癌细胞MCF-7和MDA-MB-231、人肝癌细胞Hep G2、人宫颈癌细胞HeLa均有明显的抑制活性,其半数抑制浓度(IC50)分别为17.4、12.9、20.7、24.6μmol/L;此外,2-二茂铁基乙醇对人正常乳腺上皮细胞MCF-10A没有毒性,而阳性对照药物5-氟尿嘧啶展现出了一定的毒性。Acetyl ferrocene was prepared by Friedel-Grafts acylation reaction between ferrocene and acetic anhydride.Then,ferrocenylacetic acid was synthesized by Willgerodt-Kindler reaction of acetyl ferrocene.Target compound 2-ferrocenylethanol was obtained by reduction reaction of ferrocenylacetic acid.The effects of reaction conditions on the yield of 2-ferrocenylethanol from ferrocenylacetic acid were studied.Under the optimum conditions of lithium aluminum hydride as reducing agent,tetrahydrofuran as solvent,n(lithium aluminum hydride)∶n(ferrocenylacetic acid)=8∶1,reaction temperature of 25℃,and reaction time of 24 h,the yield of 2-ferrocenylethanol was 82%.The in vitro activity test results showed that 2-ferrocenylethanol had obvious inhibitory activities against human breast cancer cells MCF-7 and MDA-MB-231,human liver cancer cells Hep G2,human cervical cancer cells HeLa,and the corresponding half inhibitory concentration(IC50)values were 17.4,12.9,20.7,24.6μmol/L,respectively.Additionally,2-ferrocenylethanol was nontoxic to human normal mammary epithelial cells MCF-10A,while the positive control drug 5-fluorouracil exhibited essential toxicity.

关 键 词：2-二茂铁基乙醇 Willgerodt-Kindler反应 合成 抗肿瘤活性 医药原料 

分 类 号：TQ463.23[化学工程—制药化工]