肿瘤低氧靶向性纳米药物载体的研究进展
张黎黎，刘琪，孙国辉，赵丽娇*，钟儒刚
（北京工业大学生命科学与生物工程学院环境与病毒肿瘤学北京市重点实验室，北京 100124）
摘要：低氧靶向性纳米药物载体能够将药物靶向释放于肿瘤低氧部位，使化疗药物更高效低毒地发挥抗肿瘤作用，因此已成为当前的研究热点。偶氮苯、硝基咪唑和硝基苯类化合物具有良好的低氧还原特性和常氧稳定性，被广泛用作低氧响应基团，从而实现肿瘤低氧靶向性。低氧靶向纳米载体可以对化疗药物、荧光指示剂或者光敏剂等进行包载，然后递送到肿瘤低氧区域，通过低氧响应基团的还原来实现纳米载体的裂解，从而释放出药物，发挥抗肿瘤活性。此外，一些低氧响应基团还具有放疗增敏剂的作用，可以在同一纳米药物上实现化疗和放疗的联合应用。综述了近年来开发的用于化疗药物递送及放疗、光动力治疗和肿瘤成像方面的低氧靶向纳米药物载体，为新型靶向性抗肿瘤药物的开发提供依据。
关键词：纳米载体；低氧靶向作用；抗肿瘤药物；化疗；放疗
中图分类号：TQ469, RT730.5文献标识码：A文章编号：0258-3283（2019）--
Research Progress on Nanomedicine Carriers Targeting Tumor HypoxiaZHANG Li-li, LIU Qi, SUN Guo-hui, ZHAO Li-jiao*,ZHONGRu-gang(Beijing Key Laboratory of Environmental & Viral Oncology, College of Life Science&Bioengineering, Beijing University of Technology, Beijing 100124, China), HuaxueShiji, 2019, 41(10), ～
Abstract:Hypoxia-targetingnanocarrier has become a hot research topic, because it can targetedly release drug to the hypoxic area of tumorso that the chemotherapy exerts anti-tumor effect with highefficacy and low toxicity. Azobenzene, nitroimidazole and nitrobenzene compounds have good hypoxic reduction properties and normoxic stability. So, they are widely used as hypoxic responsive groups to achieve hypoxia-targeting action on tumors.The hypoxia-targetingnanocarrier can encapsulate chemotherapies, fluorescent indicators or photosensitizers, and deliver them to the hypoxic region of tumor.Then the nanocarrierwas fragmented by the reduction of the hypoxia-responsive group followed by the release of drug exerting anti-tumor activity. In addition,some hypoxia-responsive groups act asradiosensitizers and can be used in combination ofradiotherapy with chemotherapy within the same nanocarrier.The hypoxia-targetingnanomedicinecarriers developed in recent years for chemotherapeutics deliverywas reviewed, as well as for radiotherapy, photodynamic therapy and tumor imaging, which will providereferences for the development of novel targeted anticancer drugs.
Keywords:nanocarrier; hypoxia-targeting action; anticancer drug; chemotherapy; radiotherapy
HPV与多环芳烃协同导致DNA损伤的研究
庄琢琛1，贾帅楠1，李劲涛1，崔鑫1，孙国辉1，Pramod Upadhyaya 2，赵丽娇*1，钟儒刚1
（1.北京工业大学 生命科学与生物工程学院 环境与病毒学北京市重点实验室，北京 100124；
2. 明尼苏达大学Masonic癌症中心，美国明尼苏达州 明尼阿波利斯市 55455）
摘要：苯并[a]芘(B[a]P)和人乳头瘤病毒(HPV)均是导致人类癌症的重要因素，前者是环境中广泛存在的致癌物，后者可诱导皮肤和黏膜鳞状上皮细胞异常增殖进而诱发癌症。流行病学证据表明烟草烟气与HPV协同作用可促进口咽鳞癌、头颈部鳞状细胞癌和肺癌等恶性肿瘤的发生，然而关于HPV与多环芳烃（PAHs）的协同致癌作用机制尚不明确。通过平板克隆形成实验、细胞划痕实验以及细胞侵袭实验对B[a]P和HPV的协同致癌作用进行了研究，比较了经B[a]P处理后人宫颈癌HeLa细胞(HPV阳性)和C33A细胞(HPV阴性)表型的变化；用高效液相色谱-电喷雾串联质谱法(HPLC-ESI-MS/MS)法对B[a]P导致的主要DNA加合物——二氢二醇环氧化物-N2-脱氧鸟苷(BPDE-N2-dG)进行了定量分析。结果表明，浓度为10 ～ 40 μmol/L的B[a]P能够显著促进HeLa和C33A细胞的侵袭和克隆形成能力，且呈剂量效应关系；经B[a]P处理后HeLa细胞的侵袭和克隆形成能力均显著高于C33A细胞(p<0.01)，并显著高于对照组HeLa细胞(p<0.01)。经浓度为10 μmol/L的B[a]P处理后HeLa细胞及C33A细胞中BPDE-N2-dG水平均最高，分别为（4172±124）fmol/mg DNA和 （1255±228）fmol/mg DNA；且各B[a]P处理浓度下的HeLa细胞中BPDE-N2-dG的水平均显著高于C33A细胞(p<0.01)，证明了HPV能显著促进B[a]P对DNA的损伤作用，为进一步揭示B[a]P和HPV的协同致癌作用提供了依据。不仅为B[a]P和HPV相关癌症的防治提供了新策略，而且将为癌症病因学研究提供新的方法。
关键词：苯并[a]芘；人乳头瘤病毒；协同致癌；DNA加合物；高效液相色谱-电喷雾质谱联用
中图分类号：R914.2 文献标识码：A 文章编号：0258-3283（2019）--
Synergistic Effect on DNA Damage Induced by HPV and Polycyclic Aromatic Hydrocarbons ZHUANG Zhuo-chen1, JIA Shuai-nan1, LI Jin-tao1, CUI Xin1, SUN Guo-hui1, UPADHYAYA Pramod2, ZHAO Li-jiao*1, ZHONG Ru-gang1 (1. Beijing Key Laboratory of Environmental and Viral Oncololgy, College of Life Science and Bio-Engineering, Beijing University of Technology, Beijing 100124, China; 2. Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, United States)
Abstract: Both benzo[a]pyrene (B[a]P) and human papillomavirus (HPV) are important factors inducing human cancer. The former is a carcinogen widely found in the environment, and the latter can induce cancer by resulting in abnormal proliferation of cutaneous and mucosal squamous cells. Epidemiological evidence suggests that tobacco smoke and HPV can synergistically promote the development of malignant tumors such as oropharyngeal squamous cell carcinoma, head and neck squamous cell carcinoma and lung cancer. However, the mechanism of the synergistic carcinogenesis of HPV and PAHs is unclear. Cell colony formation assay, cell scratch assay and cell invasion assay were conducted to assess the synergistic carcinogenesis of HPV and B[a]P, and the cell phenotypic changes of the human cervical carcinoma HeLa cells (HPV positive) and C33A cells (HPV negative) exposed to B[a]P. High performance liquid chromatography-electrospray tandem mass spectrometry (HPLC-ESI-MS/MS) was used to quantitatively determine the main DNA adduct caused by B[a]P, dihydroglycol epoxide-N2-deoxyguanosine (BPDE-N2-dG). The results showed that the ability of cells invasion and colony formation of HeLa and C33A were significantly promoted by 10-40 μM B[a]P with a dose-response relationship. The invasion and colony formation of B[a]P-treated HeLa cells were significantly higher than those of C33A cells (p<0.01) and those of HeLa cells without B[a]P treatment (p<0.01). The group treated with 10 µM B[a]P in HeLa cell and C33A cell induced the highest levels of BPDE-N2-dG, 4172±124 fmol/mg DNA and 1255±228 fmol/mg DNA, respectively. The levels of BPDE-N2-dG in HeLa cells treated with B[a]P were significantly higher than those in C33A cells (p<0.01). These combined results suggest that HPV could effectively promote DNA damage induced by B[a]P, which provide a reasonable explanation for the results of cellular experiments described above. It provides not only a new strategy for the prevention and treatment of B[a]P and HPV-related cancer, but also a new method for cancer etiology research.
低氧激活偶氮苯类AGT抑制剂的合成及还原性研究
余然，张黎黎，孙国辉，崔鑫，任婷，赵丽娇*，钟儒刚
（北京工业大学 生命科学与生物工程学院学院 环境与病毒学北京市重点实验室，北京 100124）
摘要： O6-烷基鸟嘌呤-DNA烷基转移酶（AGT）是一种重要的DNA修复酶，AGT在保护正常细胞DNA不受烷化剂损伤的同时，也能够修复抗癌烷化剂对肿瘤细胞DNA的损伤，进而导致抗肿瘤药物的耐药性。设计合成了一类具有肿瘤低氧靶向性的AGT抑制剂，该类化合物能够特异性地在肿瘤低氧环境中被还原，释放AGT抑制剂——O6-3-氨基苄基鸟嘌呤（ABG）；而在常氧条件下不能被激活，不能发挥AGT抑制作用。因此，该类化合物可与氯乙基亚硝基脲等烷化剂联合用药，通过靶向性地抑制肿瘤低氧区域中AGT的活性，提高肿瘤细胞对抗癌烷化剂的敏感性。设计合成了4种以偶氮甲苯衍生物为低氧激活基团的O6-烷基鸟嘌呤衍生物。经过体外实验模拟实体瘤中的低氧环境，确证了4种化合物均能够选择性地在低氧条件下被还原为AGT抑制剂——ABG；4种目标化合物的还原活性为：(E)-6-((3-((4-(二丙基氨基)苯基)二氮烯基)苄基)氧基)-9H-嘌呤-2-胺>(E)-(3-((4-(二丙基氨基)苯基)二氮烯基)苯基)甲醇>(E)-6-((3-((4-(乙基氨基)苯基)二氮烯基)苄基)氧基)-9H-嘌呤-2-胺>(E)-(3-((4-(乙基氨基)苯基)二氮烯基)苯基)甲醇，为开发新型靶向性抗肿瘤药物以及设计高效低毒的联合用药策略提供了新的思路。
关键词：O6-烷基鸟嘌呤-DNA-烷基转移酶；低氧激活；AGT抑制剂；肿瘤靶向性；偶氮基团
中图分类号：R914.5 文献标识码：A 文章编号：0258-3283（2019）--
Synthesis and Reduction Activity Evalution of Hypoxia-activated Azobenzene AGT Inhibitors YU Ran, ZHANG Li-li, SUN Guo-hui, CUI Xin, REN Ting, ZHAO Li-jiao*, ZHONG Ru-gang (Beijing Key Laboratory of Environmental and Viral Oncology, College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China), Huaxue Shiji, 2019, 41( ), ～
Abstract：O6-Alkylguanine-DNA alkyltransferase (AGT) is an important DNA repair enzyme. AGT can lead to drug resistance of chemotherapy by repairing DNA damages of tumor cells, while it also protects normal cell DNA from the damages induced by alkylating agents. Design and synthesize a series of AGT inhibitors with tumor hypoxia targeting that can be specifically reduced in tumor hypoxic environments, releasing the AGT inhibitor, O6-3-aminobenzylguanine (ABG). The compounds cannot be activated and exert AGT-inhibiting activity under normoxic conditions. Therefore, the compounds can be used in combination with alkylating agents, such as chloroethylnitrosourea, to increase the sensitivity of the tumor cells to chemotherapy by targetingly inhibiting the AGT activity in tumor hypoxia areas. Four O6-alkylguanine derivatives with azotoluene moiety as hypoxia-activating groups were designed and synthesized. After in vitro experiments to simulate the hypoxic environment in solid tumor, it was confirmed that the four compounds can be selectively reduced to AGT inhibitor (ABG) under the hypoxic conditions, and the reducing activity of the four target compounds was (E)-6-((3-((4-(dipropylamino)phenyl)diazenyl)benzyl)oxy)-9H-purin-2-amine > (E)-6-((3-((4-(ethylamino)phenyl) diazenyl)benzyl)oxy)-9H-purin-2-amine > (E)-6-((3-((4-(diethylamino)phenyl)diazenyl)benzyl)oxy)-9H-purin-2 -amine > (E)-6-((3-((4-(methylamino)phenyl)diazenyl)benzyl)oxy)-9H-purin-2-amine. It provided new ideas for the development of novel tumor targeting chemotherapy and for the design of anti-tumor combination strategies with high-efficacy and low-toxicity.
Key words：O6-alkylguanine-DNA-alkyltransferase; hypoxia-activation; AGT inhibitor; tumor-targeting; azo group
苝四羧酸酐和聚丙烯酸包裹SiO2微球的制备与表征及其在布洛芬控释中的应用
宋玲艳，汤小玉，孙继红*
(北京工业大学 化学化工系 绿色催化与分离北京市重点实验室，北京 100124)
摘要：用致密的纳米二氧化硅球（DNSS）作为载体，通过硅烷试剂（APTES）对其表面进行改性，并引入荧光分子3,4,9,10-苝四羧酸酐（PTD）和聚丙烯酸（PAA）分别得到APTES-DNSS、PTD@DNSS和PAA@DNSS三种有机-无机杂化材料。采用XRD、FT-IR、SEM、TG、PL等分析手段分别对上述材料的结构特征和织构参数以及热稳定性和荧光性能进行了表征。并以布洛芬（IBU）为模型药物，重点考察了以PAA@DNSS为载体的pH敏感释药性能和发光行为。结果表明通过APTES改性以及表面嫁接PTD和PAA并不能改变DNSS的球形特征和约250nm的颗粒尺寸，但是通过嫁接PTD赋予了样品PTD@DNSS的荧光性能，分别在400 nm和450 nm附近出现两个发射峰，进一步负载PAA后样品PAA@DNSS则具有较强的pH敏感释药性能，特别是在pH 7.4的释药条件下，样品PAA@DNSS不仅具有较高的释药率，而且保持较强的荧光性能。上述结果说明嫁接在APTES-DNSS表面的PAA和PTD对药物释放性能和发光行为存在着较强的表面效应。
关键词: 纳米SiO2；布洛芬；荧光性能；pH敏感释放
中图分类号：O647.3 文献标识码：A 文章编号：0258-3283（2019）--
Preparation and Characterization of Perylene-3.4.9.10-tetracarboxylic-dianhydride and Polyacrylic Acid Coated Density Nano-Sio2 Microspheres and Application in Controlled Release of Ibuprofen Song Lin-yan, Tang Xiao-wu, Sun Jihong* (Beijing Key Laboratory for Green Catalysis and Separation, Department of Chemistry and Chemical Engineering, Beijing University of Technology, Beijing 100124, China) Huaxue Shiji, 2019, 41(10), ～
Abstract: Three kinds of organic-inorganic hybrid materials: APTES-DNSS, PTD@DNSS and PAA@DNSS were obtained by using density nano-silica sphere (DNSS) as a carrier via modification by silane reagent (APTES) and subsequent introduce of fluorescence molecule 3,4,9,10-perylene tetracarboxylic anhydride (PTD) and polyacrylic acid (PAA). Their structural features and texture parameters, as well as thermal stability and fluorescence properties were characterized by means of XRD, FT-IR, SEM, TG, and PL methods. Using ibuprofen (IBU) as a model drug and PAA@DNSS as a carrier, their pH-sensitive drug release performances and luminescence behaviors were emphatically investigated. The results showed that the modification of APTES and surface grafting of PTD and PAA could not change the spherical morphology of DNSS and its particle size of around 250 nm, but the fluorescence properties of PTD@DNSS were provided by grafting PTD, exhibiting two emission peaks centered at near 400 nm and 450 nm, respectively. After further loading PAA, PAA@DNSS showed the good pH-responsive behaviors. Especially, PAA@DNSS not only exhibited a higher release amount under the release condition of pH 7.4 than that pH 3.0, but also maintained strong fluorescence properties. These results demonstrated that PAA and PTD grafted on the surface of APTES-DNSS have a strong surface effect on drug release properties and luminescence behaviors.
Key words: nano-silica, ibuprofen; luminescence properties; pH-sensitive release
六方氮化硼修饰分子印迹电化学传感器检测氯氰菊酯
董泽刚a, b，兰天宇a，马丽娇a，杜海军*a，杨洋b
（贵州民族大学 a. 生态环境工程学院，b. 材料科学与工程学院，贵州 贵阳 550025）
摘要：以六方氮化硼（h-BN）修饰玻碳电极（GCE-BN）为基底，苯酚为功能单体，通过电聚合法成功制备了可用于水样中氯氰菊酯（CYP）快速检测的分子印迹聚合膜传感器。借助拉曼光谱仪和扫描探针显微镜表征聚合膜的物相组成和表面结构，采用恒电位诱导法洗脱模板分子，差分脉冲伏安法（DPV）评价传感器的灵敏度。结果表明：传感器响应电流变化值（Δi）与氯氰菊酯的浓度在2.0×10-8 ～ 3.0×10-7 mol/L范围内呈良好的线性关系，检出限低至8.5×10-9 mol/L，水样加标平均回收率在96.3% ～ 100.2%之间。该传感器制备简单，检测成本低廉、兼具良好的稳定性、选择性，具有良好应用前景。
关键词：h-BN；氯氰菊酯；苯酚；分子印迹传感器
中图分类号：O657.1 文献标识码：A 文章编号：0258-3283（2019）
Determination of Cypermethrin by Hexagonal Boron Nitride Modified Molecularly Imprinted Electrochemical Sensor DONG Ze-ganga, b，LAN Tian-yua，MA Li-jiaoa，DU Hai-jun*a，YANG Yangb (a. College of Eco-environmental Engineering, b. School of Materials Science and Engineering, Guizhou Minzu University, Guiyang 550025, China), Huaxue Shiji, 2019, 41(10),
Abstract: The h-BN modified glass carbon electrode (GCE-BN) was used as substrate and phenol was used as the functional monomer. The molecularly imprinted polymer membrane sensor was successfully prepared by electropolymerization, which can rapidly detect cypermethrin(CYP) in water samples. The phase composition and surface morphology of the polymerized membrane were characterized by Raman spectroscopy and scanning probe microscopy. The template molecules were eluted by potentiostatic induction, and the sensitivity of the sensor was evaluated by differential pulse voltammetry (DPV). The results showed that response current (Δi) of sensor had a good linear relationship with the concentration of cypermethrin in the range of 2.0×10-8 ～ 3.0×10-7 mol/L. The detection line was as low as 8.5×10-9 mol/L, and the average recovery of the water sample was between 96.3% ～ 100.2%. This sensor is simple in preparation, low cost in detection, good stability and selectivity, and has a good application prospects.
Key words: h-BN; cypermethrin; phenol; molecularly imprinted sensor
CoMoS4电极材料的制备及其电化学性能
金小青*，邢佳斌，任瑞鑫，齐亚娥
（河西学院 化学与化工学院 甘肃省高校河西走廊特色资源利用省级重点实验室，甘肃 张掖 734000）
摘要：以钼酸钠、氯化钴为原料，采用简单化学沉淀法制备前驱体CoMoO4，然后将CoMoO4和Na2S通过离子交换反应合成双金属硫化物CoMoS4。采用X射线衍射（XRD）、扫描电镜（FESEM）、比表面积测试（BET）表征了产物的组成、结构和形貌，用循环伏安、恒电流充放电等测试方法对电极材料的电化学性能进行了研究。结果表明，当电流密度为1 A/g时，CoMoS4电极材料的比电容值为456 F/g，是Co-S的2.8倍，Mo-S的1.4倍；且1000次循环后，比电容仍保持88%，该电极材料显示出良好的电化学性能。
关键词：电极材料；CoMoS4；离子交换法；电容性能
中图分类号：O646 文献标识码:A 文章编号：0258-3283（2019）
Preparation and Electrochemical Properties of CoMoS4 Electrode Materials JIN Xiao-qing*, XING Jia-bin, REN Rui-xing, QI Ya-e (Key Laboratory of Hexi Corridor Resourses Utilization of Gansu, Department of Chemistry, Hexi University, Zhangye 734000, China), Huaxue Shiji, 2019, 41（10）
Abstract: By using NaMoO4∙2H2O and CoCl2∙6H2O as raw materials, the CoMoO4 precursor was synthesized via a chemical co-precipitation method. Then the CoMoO4 precursor and Na2S was ion-exchanged to form bimetallic sulfide of CoMoS4. In this work, the composition, microstructure and morphology of the samples were systematically characterized by X-ray diffraction (XRD), Field emission scanning electron microscopy (FE-SEM) and Brunner−Emmet−Teller (BET) measurement. The electrochemical performance were investigated by cyclic voltammetry and constant current charge/discharge techniques. The results show that the CoMoO4 electrode material has excellent electrochemical performance. The composites have a superior specific capacitance of 456 F/g at 1A/g, which is 2.8 times of the Co-S nanoparticles and 1.4 times of the Mo-S nanoparticles, and remains about 88% of the initial capacitance after 1000 cycles at current density of 1 A/g, indicating the CoMoS4 composite of excellent electrochemical performance.
Key words: electrode material；CoMoS4；ion exchange；capacitance performance
碱土金属掺杂类石墨相氮化碳的可见光催化性能研究
艾兵*，李思源，刘凡，韩永磊，李德刚
(山东理工大学 化学化工学院，山东 淄博 255049)
摘要：采用热聚合法，以三聚氰胺为前驱体合成类石墨相氮化碳（g-C3N4）光催化剂。并用同样的方法分别以掺入0.5 wt% MgCl2、CaCl2、BaCl2的三聚氰胺为前驱体合成M/ g-C3N4（M ＝ Mg、Ca、Ba）复合光催化剂。使用X射线衍射（XRD）、傅里叶变换红外光谱（FT-IR）、紫外可见漫反射（UV-Vis DRS）、扫描电子显微镜（SEM）等对所制备的光催化剂进行表征。在可见光照射下，通过光催化降解亚甲基蓝（MB）溶液研究碱土金属的掺杂对g-C3N4光催化活性的影响。研究表明，Mg、Ca、Ba等碱土金属的掺杂对g-C3N4的光催化活性分别提升了5.09、3.66、2.19倍。
关键词：热聚合，g-C3N4，碱土金属，光催化
中图分类号： O643 文献标识码：A 文章编号：0258-3283（2019）--
Visible-light Photocatalysis of Alkaline-earth Metals-doped Graphitic Carbon Nitride AI Bing*, LI Si-yuan, LIU Fan, HAN Yong-lei, LI De-gang (School of Chemistry and Chemical Engineering, Shandong University of Technology, Shandong 255049, China), Huaxue Shiji, 2019, 41（10）
Abstract: The graphitic carbon nitride (g-C3N4) photocatalyst was prepared in this work by used thermal polymerization method. Moreover, the M/g-C3N4 (M =Mg, Ca, Ba) composite photocatalyst was prepared by adding 0.5 wt% of MgCl2, CaCl2, BaCl2. The samples were characterized by X-ray diffraction (XRD), fourier transform infrared spectroscopy (FT-IR), UV-visible diffuse reflectance spectroscopy (UV-Vis DRS) and scanning electron microscopy (SEM). The effect of alkaline-earth metals-doped g-C3N4 on the photocatalytic activity was investigated by degradation of methylene blue under the visible light irradiation. The M/g-C3N4 showed the photoactivity of MB evolution 5.09 times, 3.66 times and 2.19 times higher than g-C3N4 under the 0.5 wt% doped of Mg, Ca, Ba respectively.
Key words: thermal polymerization; g-C3N4; alkaline-earth metals; photocatalysis
芦荟大黄素唑类衍生物的合成及抗肿瘤作用研究
曹丽华a，沈庆坤b，全哲山*b
（延边大学医学院 a.药理教研室，b.药学院，吉林 延吉 132002）
摘要: 以天然产物芦荟大黄素为先导化合物，设计、合成了6个未见报道的芦荟大黄素唑类衍生物，结构经核磁共振氢谱、碳谱和质谱确证。以5-氟尿嘧啶（5-Fu）为阳性对照药，采用MTT比色法进行化合物抑制人体结肠癌细胞HCT116的体外活性测试。结果表明，大部分目标化合物对结肠癌细胞的抑制活性强于先导化合物芦荟大黄素，其中3-(((1H-1,2,4-三唑-3-基)硫基)甲基)-1,8-二羟基蒽-9,10-二酮、3-(((5-氨基-4H-1,2,4-三唑-3-基)硫基)甲基)-1,8-二羟基蒽-9,10-二酮对HCT116细胞的半数抑制浓度(IC50)分别为15.18、14.15 μmol/L，明显强于阳性对照药5-Fu (IC50为24.80 μmol/L)。
关键词：芦荟大黄素；唑类；合成；抗肿瘤作用
中图分类号：R914.5 文献标识码：A 文章编号： 0258-3283（2019）
Synthesis and Antitumor Activity of Aloeemodin-azole Derivatives CAO Li-hua a, SHEN Qing-kunb,QUAN Zhe-shan *b (1. Clinical Department of Pharmacy, The 95 Hospital of PLA, Putian Fujian 351100, China; 2. Department of Pharmacology, Yanbian University College of Medicine, Yanji 133002, China; 3. College of Pharmacy, Yanbian University, Yanji 133002, China
Abstract: Six unidentified aloe-emodin azole derivatives were designed and synthesized with the natural product aloe-emodin as the lead compound. Their structures were confirmed by 1H- NMR, 13C- NMR spectra,and MS. The in vitro antiproliferative activity of the compounds in the HCT116 cancer cell lines was evaluated via MTT assay and the 5-Fu as a positive control drug. The results showed that most of the target compounds inhibited colon cancer cells more stronger than the lead compound aloe-emodin. The half-inhibitory concentrations (IC50) of compounds 1a and 1c on HCT116 cells were 15.18 and 14.15 μM, respectively, which were significantly stronger than the positive control drug 5-Fu (IC50 is 24.80 μM).
Keywords: aloe emodin; azole; synthesis; antitumor activity
以邻苯二胺为底物合成苯并咪唑类化合物的方法研究
牟杰*1, 2，孟思寒1，赵宇2，张鹏鹏2，刘杰2
(1.徐州医科大学 药学院，江苏 徐州 221000；2. 江苏省新药研究与临床药学重点实验室，江苏 徐州 221000)
摘要：苯并咪唑是重要的药效团和优势骨架，探索苯并咪唑类衍生物的高效合成方法对药物生产具有重要意义。参考国内外文献，对以邻苯二胺为底物合成苯并咪唑衍生物的方法进行综述。邻苯二胺与醛和腈的反应活性较高，与酸和酯的反应活性较低，产物的选择性依赖于催化体系。绿色合成与光催化相结合的方法可以更有效地合成苯并咪唑衍生物。系统地总结和评述了近年来对以邻苯二胺为底物合成苯并咪唑衍生物的方法，并对其未来发展方向进行展望。
关键词：邻苯二胺；苯并咪唑；合成
中图分类号：O626.2, R914.5 文献标识码：A 文章编号：0258-3283（2019）--
Synthesis of Benzimidazoles with O-phenylenediamine as Substrate MOU Jie* 1, 2 , MENG Si-han 1, ZHAO Yu 2, ZHANG Peng-peng 2, LIU Jie 2(1 School of Pharmacy, Xuzhou Medical University, Xuzhou 221000, China 2 Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou 221000, China), Huaxue Shiji, 2019, 41( 10), ～
Abstract: Be
nzimidazole is an important pharmacophore and privileged structure which has been widely utilized in pharmaceuticals and medicinal chemistry. Due to its extensive applications, the efficient synthetic approaches of benzimidazole derivatives have attracted much attention and make great progress in recent years. This review summarizes the latest information available on the synthesis of benzimidazole derivatives from o-phenylenediamine as substrate which include the conventional as well as green synthetic approach. The synthesis of benzimidazoles from o-phenylenediamine with aldehyde or nitrile showed higher activity than the other carbonyl compounds such as acid or esters. The chemoselectivity of the terminal product depends on the catalyst system. The combination of green chemistry and photocatalysis is helpful to develop more effective synthesis methods of benzimidazole derivatives. The progresses in synthetic methodologies of benzimidazole have been reviewed which can promote its application in drug development.
Key words: benzimidazole; o- phenylenediamine; synthesis
红外镜面反射炉-顶空-气相色谱-质谱法测定不同部位烟叶烟气挥发性化学成分
赵辉，赵杨，李娟，高晓华，周国福，唐石云，申钦鹏*
（云南中烟工业有限责任公司技术中心 云南省烟草化学重点实验室，云南 昆明 650231）
摘要：为简化样品前处理操作步骤，减小分析误差，采用红外镜面反射炉模拟卷烟抽吸过程，基于该装置建立了测定烟叶烟气挥发性化学成分含量的红外镜面反射炉-顶空-气相色谱-质谱（HS-GC/MS）方法，并采用该方法对不同部位烟叶的烟气挥发性化学成分进行了测定。结果表明，利用红外镜面反射炉可模拟卷烟抽吸过程，直接对捕集烟叶烟气挥发性化学成分进行分析，避免了烟支卷制、提取和浓缩过程的干扰；3个部位烟叶样品中醛酮类、酸类、烃类和杂环类挥发性成分含量较高，而醇类、酯类和酚类挥发性成分含量较低；3个部位烟叶常规挥发性成分主要在含量上存在差异，而微量挥发性成分存在明显差异，每个部位烟叶样品分别含有大量不同特有微量挥发性成分。
关键词：红外镜面反射炉；顶空-气相色谱-质谱联用仪；烟叶；挥发性化学成分
中图分类号：O656．3 文献标识码：A 文章编号：0258-3283（2019）
Determination of Volatile Constituents in Mainstream Smoke from Leaves of Different Stalk Positions by Infrared Specular Reflectance Furnace and HS-GC-MS ZHAO Hui, ZHAO Yang, LI Juan, GAO Xiao-hua, ZHOU Guo-Fu, TANG Shi-yun, SHEN Qin-peng* (Key Laboratory of Tobacco Chemistry of Yunnan Province, Research and Development of Center, China Tobacco Yunnan Industrial Co., Ltd., Kunming 650231, China), Huaxue Shiji, 2019, 41（10）
Abstract: To simplify sample preparation and reduce analysis errors, an infrared specular reflectance furnace was used to simulate cigarette smoking process, and the infrared specular reflectance furnace and headspace-gas chromatographic-mass spectrometry (HS-GC-MS) was developed to determine the levels of volatile constituents in mainstream smoke from leaves of different stalk positions. The results showed that: The volatile constituents in mainstream smoke could be analyzed directly based on the infrared specular reflectance furnace, and the rolled, extracted and concentrated were avoided. The levels of aldoketones, acids, hydrocarbons and heterocycles in mainstream smoke from leaves of different stalk positions were higher, while the levels of alcohols, esters and phenols were relatively low. The volatile constituents in mainstream smoke from leaves of different stalk positions were different in content, but there were significant differences in trace volatile compounds, the tobacco leaf in each stalk position contain more specific trace cigarette smoke volatile chemical components, respectively.
Key words: infrared specular reflectance furnace; Headspace-gas chromatography-mass spectrometry (HS-GC/MS); tobacco leaf; volatile constituents
3-[2-氯-4-(三氟甲基)苯氧基]苯甲酸的高效液相色谱分析研究
赵艳芳*1, 2，赵鹏1，常超2，孔繁蕾1
（1. 江苏省农用激素工程技术研究中心，江苏 常州213022; 2. 青岛农业大学 化学与药学院，山东 青岛266109）
摘要：3-[2-氯-4-(三氟甲基)苯氧基]苯甲酸是生产含氟二苯醚类除草剂的重要中间体，建立了一种高效液相色谱检测3-[2-氯-4-(三氟甲基)苯氧基]苯甲酸的新方法。使用Hypersil ODS柱和二极管阵列检测器，以V（乙腈）：V（0.2%磷酸水溶液） ＝ 70：30为流动相，在214 nm波长下对3-[2-氯-4-(三氟甲基)苯氧基]苯甲酸进行了外标法定量分析。在1.0 ～ 20.0 mg/L 范围内，3-[2-氯-4-(三氟甲基)苯氧基]苯甲酸的峰面积与进样浓度呈线性关系，线性相关系数为0.9994，加标回收率在98.0 ~ 103%之间, 相对标准偏差小于1.2%。所建立的液相色谱方法简便、准确，适用于3-[2-氯-4-(三氟甲基)苯氧基]苯甲酸的定量分析与质量控制。
关键词：3-[2-氯-4-(三氟甲基)苯氧基]苯甲酸；高效液相色谱；检测
中图分类号：O657.7 文献标识码：A 文章编号：0258-3283（2019）--
Determination of 3-[2-Chloro-4- (Trifluoromethyl) Phenoxy]Benzoic Acid by HPLC ZHAO Yan-fang*1, 2, ZHAO Peng1, Chang Chao2, KONG Fan-lei1 (1. Jiangsu Agricultural Hormone Engineering Technology Research Center, Changzhou 213022, China; 2. College of Chemistry and Pharmaceutical Science, Qingdao Agricultural University, Qingdao 266109, China), Huaxue Shiji, 2019, 41( ), ～
Abstract: A high performance liquid chromatographic (HPLC) method has been developed for determination of 3-[2-chloro-4-(trifluoromethyl) phenoxy]benzoic acid. The method used a Hypersil ODS column and a photodiode array detector. The mobile phase comprised acetonitrile and 0.2% phosphoric acid aqueous solution (70:30, v/v) and detection was performed at 214 nm. The linear range of determination for 3-[2-chloro-4-(trifluoromethyl)phenoxy]benzoic acid was 1.0 ~ 20.0 mg/L, showing the correlation coefficient of 0.9994. The recovery rate was 98.0 ~ 103% with the RSD < 1.2%. The presented method is suitable for routine analysis and quality control of 3-[2-chloro-4-(trifluoromethyl) phenoxy]benzoic acid in industrial production process.
Key words: 3-[2-chloro-4-(trifluoromethyl)phenoxy]benzoic acid; HPLC; Determination
GC/MS法测定卷烟爆珠中挥发性香味成分含量的研究
郭华诚，孙觅，李阳光，李怀奇*，吴艳艳*
（河南中烟工业有限责任公司，河南 郑州 450016）
摘要：为研究卷烟爆珠中挥发性香味成分，采用离心-萃取的方式对爆珠进行处理，优化萃取条件，建立了一种气相色谱质谱联用（GC/MS）技术测定爆珠中9种挥发性香味成分的方法。结果表明，萃取剂为乙醇，选用机械振荡方式，振荡时间为40 min，料液比为1 g：60 mL时萃取效果较好，目标化合分离效果较高，相关系数>0.999，回收率为96.29％～118.58％，相对标准偏差（RSD）为1.72％ ～ 2.96％，检出限为0.035 ～ 0.044 μg/mL，定量限为0.118 ～ 0.146 μg/mL。方法前处理快捷简便，灵敏度高，可满足爆珠中挥发性香味成分的分析测定，为爆珠卷烟的研发和质量评价提供参考。
关键词：爆珠；离心-萃取；挥发性香味成分；气相色谱质谱联用（GC/MS）
中图分类号：O0657.7+1 文献标识码：A 文章编号：0258-3283(2019)
The Study of Volatile Aroma Components in Cigarette Breakable Capsule by GC/MS Guo Hua-cheng, SUN Mi, LI Yang-guang, LI Huai-qi *, WU Yan-yan* (China Tobacco Henan Industrial Co., Ltd., Zhengzhou 450016, China), Huaxue Shiji, 2019, 41( 10), ～
Abstract: In order to study the volatile aroma components in cigarette breakable capsule, the breakable capsule was treated by centrifugal-extraction method, the extraction conditions were optimized, and a method for the determination of nine volatile aroma components in breakable capsule by gas chromatography-mass spectrometry (GC/MS). The results showed that the extractant was ethanol, mechanical oscillation; the oscillation time was 40 min; the ratio of material to liquid was 1g: 60mL; the extraction was better; the target compounding separation were higher; the correlation coefficient was greater than 0.999; the recovery was 96.29% ～ 118.58%; the relative standard deviation was 1.72% ～ 2.96%; the detection limit was 0.035 ～ 0.044μg/mL; and the limit of quantification was 0.118 ～ 0.146 μg/mL. The method had the advantages of quick and simple pretreatment, high sensitivity, and can meet the analysis and determination of volatile aroma components in the beading, and can provide reference for the development and quality evaluation of the beaded cigarette.
Key words: breakable capsule; centrifugation-extraction; volatile aroma components；gas chromatography-mass spectrometry
四环素猝灭聚酰胺-胺荧光机理及用于测定四环素含量
郭红卫*，李岚，郝洪庆
（嘉应学院 化学与环境学院, 广东 梅州 514015）
摘要: 在pH 1.0的溶液中，四环素对聚酰胺-胺（PAMAM）的荧光有显著的猝灭作用，结合紫外-可见光谱研究发现，动态猝灭、静态猝灭和能量转移猝灭共同导致了PAMAM的荧光猝灭现象。且四环素浓度在0.25～125 µg/mL范围内与lg（F0/F）（F0是加入四环素前PAMAM的荧光强度，F是加入猝灭剂四环素后PAMAM的荧光强度）存在线性关系，回归方程为lg（F0/F）= 11.808c + 0.0029（c为四环素浓度，mg/mL），相关系数为0.9994，据此建立了一种通过猝灭PAMAM的荧光来定量测定四环素的方法。方法已被成功用于尿样中四环素的测定，加标回收率在96%～102%之间，方法检出限为12.5 ng/mL。荧光猝灭法测定尿样中四环素的灵敏度高、检出限低、回收率高，能满足尿样中痕量四环素的测定要求。
关键词: 聚酰胺-胺; 四环素; 荧光猝灭法; 猝灭机理
中图分类号：O657.39 文献标识码：A 文章编号：0258-3283（2019）--
Fluorescence Quenching of Polyamidoamine Induced by Tetracycline and Determination of Tetracycline GUO Hong-wei, LI Lan, HAO Hong-qing (School of Chemistry and Environment, Jiaying University, Meizhou 514015, China ) Huaxue Shiji, 2019, 41( ), ～
Abstract:In the solution of pH1.0, tetracycline had a significantly quenching effect on the fluorescence of polyamidoamine (PAMAM). A nonlinear Stern-Volmer (S-V) plot and UV - visible spectra suggested that dynamic quenching, static quenching, and energy transfer quenching were responsible for the fluorescence quenching of PAMAM. And the concentration of tetracycline had a linear relationship with lg F0/F (F0 is the fluorescence intensity of PAMAM without tetracycline, F is the fluorescence intensity of PAMAM with tetracycline) in the range of 0.25～125 µg/mL. Its regression equation is lg（F0/F）= 11.808c + 0.0029（c is the concentration of tetracycline, mg/mL）with acorrelation coefficient of 0.9994. A method for determining of tetracycline was established based on the fluorescence quenching effect and had been successfully used for the determination of tetracycline in urine samples. The standard recovery rate of this method is in the range of 96 %～102 % and the detection limit is 12.5 ng/mL.The determination of tetracycline content in urine samples by a fluorescence quenching has high sensitivity, low detection limit and high recovery rate and the method can meet the determination demands of trace tetracycline in urine samples.
Key words: PAMAM; tetracycline; Fluorescence quenching; Quenching mechanism
负载超细Au纳米粒子的SiO2亚微球催化活性研究
沈启慧，徐欣辰，李妙，刘曼，刘岩*
（吉林化工学院 化学与制药工程学院，吉林 吉林 132022）
摘要：以表面裸露的银纳米粒子为牺牲剂，利用金属置换反应制备了二氧化硅亚微球负载的Au超细纳米粒子（~1 nm），并通过HRTEM和XPS表征得以证实。该复合材料作为催化剂，在乙醇中以H2O2为氧化剂催化苯乙烯环氧化时，苯乙烯的转化率达到46.7%，选择性达到91.7%，重复催化10个循环后催化活性和选择性没有观察到显着降低。本研究为苯乙烯环氧化反应使用绿色氧化剂和溶剂提供了一种新的高新能可回收的催化剂。
关键词：金；超细纳米粒子；二氧化硅亚微球；苯乙烯环氧化
中图分类号：O643.36 文献标识码：A 文章编号：0258-3283（2019）
Catalysis of Au Nanoparticles Supported on SiO2 Sub-microspheres SHEN Qi-hui, XU Xin-chen, LI Miao, LIU Man, LIU Yan* (Department of Chemistry and Pharmaceutical Engineering, Jilin Institute of Chemical Technology, Jilin 132022, China), Huaxue Shiji, 2019, 41（10）
Abstract: Au nanoparticles (AuNPs, ~1 nm) supported on silica sub-microspheres were synthesized via metal displacement reaction and the bare silver nanoparticles as sacrificial agent. The structurers were confirmed by HRTEM and XPS. The application in styrene epoxidation were introduced. The conversion and selectivity of styrene reached 46.7% and 91.7% when the composite was used as catalyst for styrene epoxidation in ethanol with hydrogen peroxide as oxidant. The catalytic activity and selectivity did not decrease significantly after 10 cycles of reused catalysis. This composite was a new and recyclable catalyst for the epoxidation of styrene using green oxidants and solvents.
Key words: Au；ultrafine nanoparticles；SiO2 sub-microspheres；styrene epoxidatio
以柠檬酸为成孔剂制备微孔-介孔ZSM-5分子筛的研究
徐玲，张强，路广，张淼，李丹丹，刘宗瑞
（内蒙古民族大学 化学化工学院，内蒙古 通辽 028000）
摘要：采用NaOH溶液对ZSM-5分子筛进行不同时间预处理，再以柠檬酸为成孔剂，在水热条件下合成了微孔-介孔ZSM-5分子筛，考察碱处理时间对分子筛内部孔道结构的影响。同时测试了该类型的分子筛在苯酚叔丁基化反应中的催化活性。结果表明，ZSM-5分子筛经1 mol/L的NaOH溶液处理1 h后加入柠檬酸搅拌2 h，于100 ℃条件下晶化24 h所形成的微孔-介孔ZSM-5分子筛具有良好的微孔和介孔复合结构。在苯酚叔丁基化反应中表现出良好的催化性能，在反应温度为418 K时苯酚的转化率为85.6%，2,4-二叔丁基苯酚的选择性为60.2%。
关键词：微孔-介孔ZSM-5分子筛；柠檬酸；2,4-二叔丁基苯酚
中图分类号：O643 文献标识码：A 文章编码：0258-3283（2019）--
Preparation of Micro-mesoporous ZSM-5 Molecular Sieves using Citric Acid as Pore-forming Agent XU Ling, ZHANG Qiang, LU Guang, ZHANG Miao, LI Dan-dan, LIU Zong-rui (College of Chemistry and Chemical Engineering, Inner Mongolia University for Nationalities, Tongliao Inner Mongolia, 028000, China)
Abstract: ZSM-5 Zeolite was pretreated with sodium hydroxide solution for different time, and citric acid was used as a pore-forming agent. Micro-mesoporous ZSM-5 zeolite was prepared under hydrothermal conditions. The alkali treatment time was investigated on the structure of the molecular sieve. At the same time, the catalytic activity of the micro-mesoporous ZSM-5 molecular sieves in tert-butylation of phenol was tested. The results showed that ZSM-5 zeolite treated with 1 mol/L NaOH solution for 1 h, and the micro-mesoporous ZSM-5 formed at 24 h and 100 °C had better micro-mesoporous structure. The sample of 1 h -ZSM-5 exhibited better catalytic performance in the tert-butylation reaction of phenol. The conversion of phenol was 85.6% at a reaction temperature of 418 K, and the selectivity to 2,4-di-tert-butylphenol was 60.2%.
Key words: micro-mesoporous ZSM-5; citric acid; 2,4-di-tert-butylphenol
手性硫脲-酰胺的合成及其在Michael加成反应中的应用
杨静，白冰*，张改红，毛多斌
(郑州轻工业学院 食品与生物工程学院，河南 郑州 450000)
摘要：以3, 5-双(三氟甲基)苯基异硫氰酸酯、1, 2-二胺和取代脯氨醛为原料，经过加成、还原氨化等反应，合成了一系列新型硫脲-酰胺有机小分子催化剂，利用核磁、红外、质谱（1HNMR、13CNMR、IR、MS）等对化合物结构进行了表征，并对其催化2, 4-戊二酮对各种取代硝基烯烃的不对称Michael加成反应进行了研究。结果表明，以甲苯为溶剂，在催化剂用量为1 mol%的情况下，Michael加成产物具有较高的产率（最高95%）和对映选择性（最高e.e. 91%）。
关键词：硫脲-酰胺；有机催化剂；Michael加成
中图分类号：O621.3 文献标识码：A 文章编号：0258-3283（2019）--
Synthesis of Thiourea-amide Organocatalysts and Application in Enantioselective Michael Addition YANG Jing, BAI Bing*, ZHANG Gai-hong, MAO Duo-bin (School of Food & Biological Engineering, Zhengzhou University of Light Industry, Zhengzhou 450000, China), Huaxue Shiji, 2019, 41（10）
Abstract：Several bifunctional chiral thiourea-amide organocatalysts were synthesized from 1, 2-diamine, 1-sothiocyanato-3,5-bis(trifluoromethyl) benzene and N-substitute prolinol. The structures were confirmed by 1HNMR, 13CNMR, IR, MS. They were used as chiral catalysts in asymmetric Michael conjugate addition of acetylacetone to various nitroalkenes. The result shows that the desired Michael addition products were obtained in present of organocatalyst 1 mol% in high yields (up to 95%) and enantioselectivities (up to 91% e.e.).
Key words：thiourea-amide; organocatalyst; Michael addition
高分散CeO2@C核壳材料催化2-取代苯并噻唑的合成研究
项东升*1,朱驯1, 秦恒飞2,周红军3
（1. 盐城工业职业技术学院 化学工程系，江苏 盐城 224005；2. 江苏理工学院 化学与环境工程学院，江苏 常州 213001；3 .江苏天宇检测技术有限公司，江苏 盐城 224005）
摘要:以木质素低聚物前体，在氩气下在600℃下碳化制备了高度分散CeO2@C核壳材料催化剂，并对催化剂进行了X-射线衍射分，拉曼光谱（Raman），透射电镜（TEM）表征，催化剂核壳结构的限域作用与较高的石墨化程度，提高了催化剂的稳定性和催化活性。研究了CeO2@C核壳材料催化剂在以纯O2为氧化剂下，由邻氨基苯硫酚和醛类缩合而得到2-取代苯并噻唑，通过单因素条件实验，确定了合成标题化合物的工艺条件，并获得良好的收率。
关键词: CeO2@C；核壳材料; 催化; 邻氨基苯硫酚;醛; 2-取代苯并噻唑
中图分类号：TQ252.5 文献标识码：A 文章编号：0258-3283（2019）--
Highly Dispersed CeO2@C Core-Shell Nanoparticles as Efficient Catalyst for Synthesis of 2-Substitutedbenzothiazoles XIANG Dong-sheng*1, ZHU Xun1, QIN Heng-fei2, ZHOU Hong-jun3(1. Department of Chemistry Engineering, Yancheng Institute of Industry Technology, Yancheng 224005, China; 2. School of Chemistry and Environment Engineering, Jiangsu University of Technology, Changzhou 213001, China; 3. Jiangsu Tianyu Detection Technology Co.,Ltd, Yancheng 224005), Huaxue Shiji, 2019, 41(10), ～
Abstract: The highly dispersed CeO2@C Core-Shell Nanoparticles was prepared by Lignin-Based Oligomer Precursors under argon at 600 °C. The catalysts were characterized by X-ray diffraction, energy-dispersive X-ray spectrometry, transmission electron microscopy, nitrogen adsorption-desorption, and Raman spectrum. The limited function of the catalyst core-shell structure and the higher degree of graphitization improve the stability and catalytic activity of the catalyst. o-aminothiophenol and aldehydes to achieve condensation Benzothiazole Derivatives by O2 as Oxidation and CeO2@C Core-Shell Nanoparticles as catalyst derivatives. The process conditions for the synthesis of the target product were determined by a single factor conditional experiment, and a good yield was obtained.
Key words: CeO2@C; core-shell material; catalysis; o-aminothiophenol; aldehydes; 2-substitutedbenzothiazoles
塑化剂残留检测用内标试剂邻苯二甲酸二苯酯-D4
的合成研究
徐仲杰1, 2，涂亚辉1, 2，邓晓军3，孙雯1, 2，古淑青3，白少飞1, 2，赵超敏3，罗勇*1, 2
(1. 上海化工研究院有限公司，上海 200062；2. 国家同位素工程技术研究中心上海分中心，上海 200062；3. 上海市检验检疫科学技术研究院，上海 200135)
摘要：以廉价易得的邻二甲苯-D10为标记前体，经过氧化、氯化、酯化三步反应，合成得到标题化合物。通过单因素对实验关键步骤进行优化，得到了较优的合成工艺，以消耗的标记试剂邻二甲苯-D10计算，标题化合物的总收率为75.2%。采用高效液相色谱（HPLC）、质谱（MS）、核磁共振（NMR）进行了结构确认，色谱纯度大于99.0%，同位素丰度大于99.0% atom D。标题化合物可应用于食品中塑化剂残留的检测、人体中塑化剂代谢示踪、环境中塑化剂降解机理研究等领域。
关键词：邻苯二甲酸二苯酯-D4；同位素标记；内标；合成
中图分类号：0652.1 文献标识码：A 文章编号：0258-3283（2019）
Synthesis of the Internal Standard Reagent Diphenyl Phthalate-D4 for Plasticizer Residue Test XU Zhong-jie1, 2, TU Ya-hui1, 2, DENG Xiao-jun3, SUN Wen1, 2, GU Shu-qing3, BAI Shao-fei1, 2, ZHAO Chao-min3, LUO Yong*1, 2 (1.Shanghai Research Institute of Chemical Industry CO.,LTD., Shanghai 200062, China; 2.National Isotope Engineering Technology Research Center-Shanghai Sub-Center, Shanghai 200062, China; 3.Shanghai Research Institute of Inspection and Quarantine Science and Technology, Shanghai 200135, China), Huaxue Shiji, 2019, 41（10）
Abstract：This work presents an efficient and convenient synthesis method of diphenyl phthalate-D4 with o-xylene-D10 as the common substrate, which is mainly obtained by three steps of oxidation, chlorination and esterification. By optimizing the key steps of the experiment via single factor optimization, a better synthetic process was obtained. The total yield of diphenyl phthalate-D4 was 75.2% based on o-xylene-D10 consumed. The structures were confirmed by Mass spectrometry (MS) and nuclear magnetic resonance (NMR). The chromatogram purity was greater than 99.0% and the isotopic abundance was greater than 99.0% atom D. The product can be applied to the detection of plasticizer residues in food, the tracer of plasticizer metabolism in human body, the degradation mechanism of plasticizer in the environment and other fields.
Key words：diphenyl phthalate-D4; isotope labeling; internal standard; synthesis
水稻螟虫信息素成分—13顺-十八碳烯醛等的合成
肖玲香1, 2，黄飞2，张玉顺1，陶云海*1, 2
(1. 云南大学 化学科学与工程学院, 云南 昆明 650091; 2. 昆明博鸿生物科技有限公司, 云南 昆明 650501)
摘要：13顺-十八碳烯醛及13顺-十八碳烯醇和乙酸13顺-十八碳烯酯是水稻螟虫的信息素成分。从十二碳二醇出发，经单酯化和氧化得到乙酸12-氧代十二碳酯，经Wittig反应得到乙酸12顺-十七碳烯酯，再经水解和氧化得到12顺-十七碳烯醛，与甲氧基甲基三苯基氯化膦进行Wittig反应得到13顺-1-甲氧基十八碳-1,13-二烯，水解得到13顺-十八碳烯醛，再经还原和乙酯化分别得到13顺-十八碳烯醇和乙酸13顺-十八碳烯酯。
关键词：水稻螟虫；信息素合成；13顺-十八碳烯醛；13顺-十八碳烯醇；乙酸13顺-十八碳烯酯；Wittig反应
中图分类号：O623 文献标识码：A 文章编号：0258-3283（2019）--
Syntheses of 13Z-Octadecenal, 13Z-Octadecen-1-ol and 13Z-Octadecen-1-yl Acetate, Sex pheromone Components of Both Rice Pests Xiao Ling-xiang1, 2, Huang Fei2, Zhang Yu-shun1, Tao Yun-hai*1, 2 (1. School of Chemistry Science and Engineering, Yunnan University, Kunming 650091, China; 2. Kunming Biohome Technology Co. Ltd., Kunming 650501, China), Huaxue Shiji, 2019, 41(10 ), ～
Abstract：13Z-Octadecenal, 13Z-octadecen-1-ol and 13Z-octadecen-1-yl acetate are sex pheromone components of both rice pests. Synthesis of three compounds was achieved from 1, 12-dodecanediol. Firstly, monoesterification and oxidation of 1, 12-dodecanediol gave 12-oxododecyl acetate, which reacted with the ylide prepared from pentyltriphenylphodphonium bromide to afford 12Z-heptadecen-1-yl acetate. Hydrolysis and oxidation of the acetate gave 12Z-heptadecenal, which reacted with the ylide prepared from (Methoxymethyl)triphenylphodphonium chloride followed by hydrolysis to afford 13Z-octadecenal. Reduction of the aldehyde gave 13Z-octadecen-1-ol, which led to 13Z-octadecen-1-yl acetate by esterification.
Key words：rice pests; pheromone synthesis; 13Z-octadecenal; 13Z-octadecen-1-ol; 13Z-octadecen-1-yl acetate; Wittig reaction
盐酸氨溴索葡萄糖注射液有关物质的合成
陈仕云1，何勇*2，高永好2，彭扶云2，吴宗好2
（1.合肥学院 分析测试中心，安徽 合肥 230601；2.合肥华方医药科技有限公司，安徽 合肥 230088）
摘要：为了控制盐酸氨溴索葡萄糖注射液质量，合成了有关物质4-(6, 8-二溴-3, 4-二氢喹唑啉-3-基)-环己醇盐酸盐。以盐酸氨溴索为起始原料，与甲醛经环合、氧化两步反应合成了此有关物质，经IR、1HNMR、13CNMR及ESI-MS等波谱技术对4-(6, 8-二溴-3, 4-二氢喹唑啉-3-基)-环己醇盐酸盐进行结构确证。本合成路线方法简单、后处理方便、适合工业化生产，为盐酸氨溴索原料及其制剂杂质对照品的制备奠定了物质基础。
关键词：盐酸氨溴索；4-(6, 8-二溴-3, 4-二氢喹唑啉-3-基)-环己醇盐酸盐；有关物质；合成
中图分类号：R914.5 文献标识码：A 文章编号：0258-3283（2019）
Synthesis of Related Substances for Ambroxol Hydrochloride Glucose Injection CHEN Shi-yun1, HE Yong*2, GAO Yong-hao2, PENG Fu-yun2, WU Zong-hao 2（1. Analytical & Testing Center, Hefei University, Hefei 230601, China; 2. Hefei Huafang Pharmaceutical Science & Technology Co., Ltd., Hefei 230088, China), Huaxue Shiji, 2019, 41（10）
Abstract: To perform the quality control of ambroxol hydrochloride glucose injection, related substance 4-(6, 8-dibromo-3, 4-dihydroquinazoline-3-yl)-cyclohexanol was prepared. 4-(6, 8-Dibromo-3, 4-dihydroquinazoline-3-yl)-cyclohexanol was synthesized from ambroxol hydrochloride and formaldehyde by cyclization and oxidation reactions. The structure of 4-(6, 8-dibromo-3, 4-dihydroquinazoline-3-yl)-cyclohexanol was confirmed by IR, 1HNMR, 13CNMR and ESI-MS. The synthetic route designed in this work is simple and the post-processing is convenient, can be used to provide the material foundation for ambroxol hydrochloride related substances 4-(6, 8-dibromo-3, 4-dihydroquinazoline-3-yl) -cyclohexanol reference substance preparation．
Key words: ambroxol hydrochloride; 4-(6, 8-dibromo-3, 4-dihydroquinazoline-3-yl)-cyclohexanol; related substances; synthesis
