1、研究论文One-pot Synthesis of(E)-Diethyl 2-styrylquinoline-3,4-dicarboxylate DerivativesZhao Di1,Liu Yanying2,Wang Yang3,Li Yang1(1 College of Chemistry and Materials Engineering,Bohai University,Jinzhou,121000;2 Research Institute of Jinzhou Petrochemical Company,Jinzhou,121000;3 Center of Experiment an
2、d Equipment Management,Bohai University,Jinzhou,121000)AbstractIn the present work,a simple and flexible synthesis of a series of novel(E)-diethyl 2-styrylquinoline-3,4-dicarboxylates 3a 3i with good yields has been achieved,involving one-pot sequential Arbuzov/Horner-Wadsworth-Emmons(HWE)reaction s
3、equence using diethyl 2-(bromomethyl)quinoline-3,4-dicarboxylate as substrate.The molecular structures of these newly synthesized products were confirmed by spectral data and elemental analyses.KeywordsBromomethyl,Styrylquinoline,One-pot,Arbuzov reaction,HWE reaction“一锅法”合成(E)-2-苯乙烯基喹啉-3,4-二酸二乙酯类衍生物
4、赵 頔1 刘延鹰2 王 洋3 李 阳1(1 渤海大学化学与材料工程学院锦州121000;2 锦州石化分公司研究院锦州121000;3 渤海大学实验与设备管理中心锦州121000)联系人,李阳男,43 岁,博士,教授,主要从事有机合成研究。E-mail:bhuzh 国家自然科学基金项目(21878023,U1608222)、辽宁省特聘教授项目、辽宁省教育厅“青年育苗”项目(LQ2019006)和辽宁省科技厅博士启动项目(2019-BS-004)资助2022-07-12 收稿,2022-10-09 接受摘要本文设计以 2-溴甲基喹啉-3,4-二甲酸二乙酯为起始化合物,经一锅连续的 Arbuzov
5、反应/Horner-Wadsworth-Emmons(HWE)反应过程,简便而有效地合成了一系列结构新颖的(E)-2-苯乙烯基喹啉-3,4-二羧酸二乙酯类衍生物(3a 3i),其结构均已通过波谱数据和元素分析得以证实。关键词溴甲基苯乙烯基喹啉一锅法Arbuzov 反应HWE 反应Among a great variety of quinoline derivatives,2-styryl quinolines(SQLs)form an important type of structural motifs in medicinal chemistry and represent a signi
6、ficant component of pharmacolo-gically active molecules.Members of this family have been claimed to exhibit a wide range of biolo-gical properties,such as anticancer1,antitumor2,antimalarial3,antifungal,antibacterial4,antimi-crobial5,and anti-HIV activities6.For example,styrylquinoline FZ-41(I,Schem
7、e 1)had entered clinical trials as an inhibitor of HIV integrase7.WK14 derivative(II,Scheme 1)exhibited potent anti-C.albicans activity by selectively inhibiting the Cdr1p efflux pump8.Compounds of 8-carboxy-substituted 2-styryl quinolines(III,Scheme 1)exhibited significant antiproliferative activit
8、y against the P388 leukemia cell line9.Recently,Dhanawat et al.have described the 2-styrylquinoline structure as an elite scaffold and a wonderful pharmacophore in drug discovery10.Owing to their striking biological activities and structurally diversified molecules for bio-screening,985http:/www.hxt
9、b.org化学通报2023 年 第 86 卷 第 5 期DOI:10.14159/ki.0441-3776.2023.05.015Scheme 1Structures of some bioactive 2-styrylquinline derivatives I III图式 1具有生物活性的 2-苯乙烯基喹啉衍生物(I III)的结构considerable synthetic efforts have been made surrounding the 2-styrylquinoline structure template for further functionalization an
10、d modification by organic and medicinal chemists with the aim of enhancing the potency of this privileged class of quinolines11 14.For example,Kumar et al.15 reported the one-pot direct synthesis of(E)-ethyl 2-styrylquinoline-3-carboxylate derivatives by using In(OTf)3 as the catalyst(as shown in Sc
11、heme 2a).However,this method is not completely satisfactory since the use of expensive transition metal catalyst.In this regard,Dabiri et al.16 reported such synthesis using 1-methylimidazolium trifiuoroacetate(Hmim TFA)ionic liquid(Scheme 2a).Similarly,Sarma et al.17 exploited this synthesis employ
12、ing-SO3H functionalized ionic liquid as reaction media(Scheme 2a).Although ionic liquids have emerged as effective solvents for the chemical transformations,the high cost and their toxicity has limited their practical application.Scheme 2Synthetic methodologies for 2-styrylquinoline-carboxylates图式 2
13、2-苯乙烯基喹啉羧酸酯类化合物合成方法In light of the above reports and in view of structural diversity playing a prominent role towards new drug discovery,we envisioned that it might be a worthwhile effort to design and synthesize a new class of carboxylate functionalized 2-styrylquinoline derivatives,because it migh
14、t lead to a new dimen-sion of structural diversity as potential candidates for biological evaluations or provide more opportunities for further synthetic manipulations.Thus,in the context of our continuing interest in the construction of interesting types of quinoline-based com-pounds1823,we would l
15、ike to report herein the one-pot synthesis of a series of structurally new and intriguing(E)-diethyl 2-styrylquinoline-3,4-dicarboxylate derivatives as shown in Scheme 2b.To the best of our knowledge,the synthesis of such 2-styrylquinoline derivatives has not been achieved so far,which might be an a
16、ttractive template for further study from both a biological as well as a building block perspective.1Experimental Section1.1GeneralThe chemicals used in this work were obtained from Energy Chemical and were used without purification.Melting points were determined by use of a WRS-1B melting point apparatus and are uncor-rected.The 1H and 13C NMR spectra were recorded on an Agilent 400-MR spectrometer using CDCl3 as the solvent.The reported chemical shifts(values)are given in parts per million dow
