5-氟尿嘧啶聚乙二醇-聚十六烷基氰丙烯酸酯纳米粒的制备

目的:以聚乙二醇-聚十六烷基氰丙烯酸酯(PEG-PHDCA)聚合物制备5-氟尿嘧啶(5-Fu)纳米粒,并对其进行体外释药研究.方法:采用溶剂扩散法制备5-Fu PEG-PHDCA纳米粒,在单因素基础上采用正交设计法优化得到最佳处方,并对5-Fu聚合物纳米粒的粒径、Zeta电位、载药量、包封率和体外释放进行了研究.结果:制得的5-Fu聚合物纳米粒的平均粒径为132 nm,Zeta电位为-(12±2)V,载药量为12.3%,包封率为48.8%.体外释放研究发现,5-Fu PEG-PHDCA纳米粒释药近似符合Higuchi释药模型:Q=0.564 4+8.386t1/2(r=0.996 0).结论:采用溶剂扩散法制备5-Fu聚合物纳米粒方法简单,重现性好,其体外释放显示出明显缓释作用.     

砂蓝刺头地上部分化学成分研究

目的　研究砂蓝刺头地上部分的化学成分。方法　溶剂提取和色谱法分离纯化 ,理化性质、核磁共振波谱和质谱鉴定结构。结果　分离鉴定了 6个化合物 :蒲公英甾醇乙酸酯 ( ) ,伪蒲公英甾醇乙酸酯 ( ) ,蒲公英甾醇 ( ) ,伪蒲公英甾醇 ( ) ,β-香树脂醇乙酸酯 ( ) ,β-香树脂醇棕榈酸酯 ( )。结论　化合物 ～ 均为首次从蓝刺头属植物中分离得到     

以六氯化钨催化制备醛的二乙酸酯

醛与醋酐加催化量的 WCl6在 CH2 Cl2 中 (或不用溶剂 ) ,室温反应 3～ 15 min,高化学选择性得到醛的二乙酸酯(acylal——尚无译名 )。 10例收率 90 %以上以六氯化钨催化制备醛的二乙酸酯@裘鹏程     

Knoevenagel缩合反应新催化剂

芳醛或杂芳醛与含有活泼亚甲基的化合物（氰乙酸酯、氰乙酰胺、丙二腈）于水中在磷酸氢二铵催化下，室温搅拌即可发生Knoevenagel反应。条件温和，时间短，后处理简单，环境友好。20例收率70％～95％。     

聚乙二醇化聚氰酯毫微粒作为salvicine载体：合成、制备和体外特性

目的：合成和鉴定聚乙二醇化聚氰酯共聚物,制备聚乙二醇化聚氰酯共聚物和聚氰酯聚合物的毫微粒,测定二种毫微粒的体外特性。方法：用^1H-NMR,^13C-NMR和FTIR测定聚乙二醇化聚氰酯共聚物的结构,用凝胶渗透色谱法测定共聚物的分子量,用乳化／蒸发法制备毫微粒。结果：^1H-NMR,^13C-NMR和FTIR光谱与聚乙二醇化聚氰酯共聚物的结构相符,合成共聚物的分子量是6680,用HPLC测定毫微粒的包封效率时,共聚物对salvicine的测定无干扰,聚乙二醇化聚氰酯共聚物毫微粒的包封率是92．6％,聚氰酯聚合物的包封效率是98．9％。二种毫微粒的粒径均为250nm左右。Zeta电位值受聚合物结构的影响,与聚氰酯毫微粒比较（－23．1mV),聚乙二醇化聚氰酯毫微粒显示低的Zeta电位值（－9.6mV)。毫微粒的体外释放显示一个开始的突释效应,然后缓慢释放达28天。结论：聚乙二醇化聚氰酯毫微粒可能是salvicine体内抗肿瘤作用的一个有效载体。     

固液相烃化反应的研究——以固体碱金属碳酸盐为碱的乙酰丙酮、乙酰乙酸乙酯的烃化反应

徐成治等(化学学报 1983,41(6):514)发现并报道了在无溶剂无催化剂条件下,固体碳酸钾可以方便地用于丙二酸酯、氰乙酸酯的烃化反应。为了进一步研究以碱金属碳酸盐(M_2CO_3)为碱的活性亚甲基化合物的烃     

顶空气相色谱法测定头孢替坦二钠中的残留溶剂

目的 用毛细管气相色谱法建立头孢替坦二钠中5种残留溶剂的测定方法.方法 采用DB-624毛细管色谱柱(60m×0.32mm×1.0μm),固定相为6％氰丙基-苯基,94％二甲基聚硅氧烷,FID检测器,载气为氮气,程序升温,进样口温度200℃,检测器温度250℃,分流进样模式,测定残留溶剂的含量.结果 在各种的浓度范围内具有良好的线性关系(5种溶剂的相关系数均为0.999以上),5种溶剂3个浓度的回收率均在90.0％～110.0％之间.结论 本方法专属性强,操作简便,结果可靠,可用于5种残留溶剂的同时测定.     

GC测定盐酸克林霉素棕榈酸酯中的9种残留溶剂

目的建立毛细管气相色谱法测定盐酸克林霉素棕榈酸酯中的残留溶剂。方法乙醇、丙酮、乙腈、二氯甲烷、乙酸乙酯和三氯甲烷测定采用顶空进样法,色谱柱为DB-624(6%氰丙基苯基-94%二甲基聚硅氧烷固定液)石英毛细管柱,柱温为60℃,维持10 min,以20℃.min 1升至180℃,维持2 min,二甲基甲酰胺-水(1∶4)为溶剂;甲苯、吡啶和二甲基甲酰胺测定采用直接进样法,色谱柱为DB-624(6%氰丙基苯基-94%二甲基聚硅氧烷固定液)石英毛细管柱,柱温为90℃,二氯甲烷为溶剂。结果被测物均能得到很好的分离,峰面积与浓度呈良好的线性关系,精密度和回收率良好。结论该法可用于盐酸克林霉素棕榈酸酯原料药中残留溶剂的检测。     

工作场所空气中2-乙氧基乙基乙酸酯的气相色谱测定方法

2-乙氧基乙基乙酸酯又称乙二醇单乙醚醋酸酯,(2-ethoxyethyl acetate,2-EEA)。2-乙氧基乙基乙酯为无色具醚味无色液体,其沸点156℃,相对密度(20℃/4℃):0·973 0,微溶于水,能与芳香烃混溶。主要用途为金属、家具喷漆用溶剂和刷涂漆用溶剂。由于其毒性较苯系物等常用溶剂低,目前     

培美曲塞二钠原料药中9种残留溶剂测定方法研究

目的:建立培美曲塞二钠原料药中甲醇等残留溶剂的测定方法.方法:采用气相色谱直接进样法,FID检测器,6%氰丙基苯基-94%二甲基硅氧烷毛细管色谱柱,应用程序升温,进样口温度180℃,检测器温度250℃,载气为N2,以水和二甲基亚砜为溶剂配制对照品溶液及样品溶液,采用外标法定量.结果:9种残留溶剂在对应于限度的50%～150%浓度范围内有良好的线性关系(r=0.997 1～0.999 9),平均回收率为85.6%～101.1%.结论:方法简单、可靠、精确,可用于培美曲塞二钠原料药残留溶剂的测定.     

Selegiline-functionalized, PEGylated poly(alkyl cyanoacrylate) nanoparticles: Investigation of interaction with amyloid-β peptide and surface reorganization

Alzheimer's disease (AD) is a neurodegenerative disorder for which the research of new treatments is highly challenging. Since the fibrillogenesis of amyloid-β peptide 1-42 (Aβ_1-42) peptide is considered as a major cause of neuronal degeneration, specific interest has been focused on aromatic molecules for targeting this peptide. In this paper, the synthesis of selegiline-functionalized and fluorescent poly(alkyl cyanoacrylate) nanoparticles (NPs) and their evaluation for the targeting of the Aβ_1-42 peptide are reported. The synthetic strategy relied on the design of amphiphilic copolymers by tandem Knoevenagel-Michael addition of cyanoacetate derivatives, followed by their self-assembly in aqueous solutions to give the corresponding NPs. Different cyanoacetates were used: (i) hexadecyl cyanoacetate (HDCA) to form the hydrophobic core of the NPs; (ii) rhodamine B cyanoacetate (RCA) for fluorescent purposes; (iii) methoxypoly(ethylene glycol) cyanoacetate (MePEGCA) for stealth properties and (iv) selegiline-poly(ethylene glycol) cyanoacetate (SelPEGCA) to obtain the desired functionality. Two different amphiphilic copolymers were synthesized, a selegiline-containing copolymer, P(MePEGCA-co-SelPEGCA-co-HDCA), and a rhodamine-labelled counterpart, P(MePEGCA-co-RCA-co-HDCA), further blended at variable ratios to tune the amount of selegiline moieties displayed at the surface of the NPs.Optimal formulations involving the different amphiphilic copolymers were determined by the study of the NP colloidal characteristics. Interestingly, it was shown that the zeta potential value of the selegiline-functionalized nanoparticles dramatically decreased, thus emphasizing a significant modification in the surface charge of the nanoparticles. Capillary electrophoresis has then been used to test the ability of the selegiline-functionalized NPs to interact with the Aβ_1-42 peptide. In comparison with non functionalized NPs, no increase of the interaction between these functionalized NPs and the monomeric form of the Aβ_1-42 peptide was observed, thus highlighting the lack of availability of the ligand at the surface of the nanoparticles. A mechanism explaining this result has been proposed and was mainly based on the burial of the hydrophobic selegiline ligand within the nanoparticles core.     

吡嘧司特钾的合成

以氰乙酸乙酯为起始原料 ,与原甲酸三乙酯缩合得到 2 -氰基 - 3-乙氧基丙烯酸乙酯 ,再经与 2 -氨基 - 3-甲基吡啶环合 ,进而成盐得到吡嘧司特钾 ,总收率为 30 %。     

Die Cyanessigesterreaktion substituierter Naphthochinone. 2. Mitt.: Beitrag zum Reaktionsmechanismus

Cyanoacetate Reaction of Substituted Naphthoquinones. Part II The reaction between 2-methyl-1,4-naphthoquinone and cyanoacetate has been studied. The structure model of the sodium hydrogen sulfite derivative permits an insight into the mechanism of the reaction. NMR-spectrometry brings direct evidence for the bonding on the quinoidal skeletal structure. In accordance with the analogous model a 1,2-addition can be assumed. The reaction is base catalysed. An attack by the carbanion of cyanoacetate on C-2 of the quinoidal system takes place.     

普瑞巴林的合成

氰乙酸甲酯经缩合、加成、环化、氨解、Hoffman重排、拆分制得抗惊厥药物普瑞巴林,总收率16.1%.     

吡嘧司特钾的合成

以氰乙酸乙酯为起始原料，先与叠氮化钠反应生成5-乙氧羰甲基-1H-四唑，再与2-氨基-3-甲基吡啶和原甲酸三乙酯缩合得到吡嘧司特，进而成盐得到吡嘧司特钾，总收率38．7％。     

帕珠沙星的合成研究

以左氟沙星中间体（S）-9，10-二氟-3-甲基-7-氧代-2，3-二氢-7H-吡啶[1，2，3-de][1，4]苯并恶嗪-6-羧酸乙酯为原料，经与氰乙酸乙酯缩合、脱羧、环合、水解及Hoffman降解制得帕珠沙星，总收率43%。     

吡嘧司特钾的合成

以氰乙酸乙酯为原料，与叠氮化钠环合得到四唑-5-乙酸乙酯，再与2-氨基-3-甲基吡啶缩合得到3-(3-甲基-2-吡啶氨基)-2-(1H-四唑-5-基)丙烯酸乙酯，之后经环合成盐得到吡嘧司特钾，总收率48％。     

Studies on aminopyrazoles: antibacterial activity of some novel pyrazol

Hydrazones 2a-d were prepared from diazotiazation of sulfanilamide or its derivatives followed by coupling with ethyl cyanoacetate. 3-Aminopyrazoles 3a-d were obtained by refluxing of 2a-d with hydrazine hydrate in ethanol. [Bis(-methylthio)methylene]malononitrile (4) was reacted with aminopyrazoles 3a-d in refluxing DMF containing triethylamine to yield the novel pyrazolo[1,5-a]pyrimidines 6a-d. The anilino derivatives 8a-h were obtained by fusion of compounds 6a-d with aromatic amines. When compounds 6a,c,d were subjected to the reaction with hydrazine hydrate, the hydrazino derivatives 9a-c were isolated. Also, the aminopyrazoles 3 were reacted with some electrophiles such as arylidenemalononitriles, ethoxymethylene malononitrile and ethyl ethoxymethylene cyanoacetate to yield the novel substituted pyrazolo[1,5-a]pyrimidines 13, 17 and 19, respectively. Structures of the new compounds were established by their elemental analyses and spectral data. Most of these compounds were also tested in vitro for their antibacterial activity against some gram positive and gram negative bacteria.     

Configuration and conformation of isomeric 3,5-diaryl-4-cyano-4-methoxycarbonylcyclohexanones

Configuration and Conformation of the Isomers of 3.5-Diaryl-4-cyano-4-methoxycarbonyl-cyclohexanones The steric behaviour of the reaction products from the addition of methyl cyanoacetate to some 1.5-diaryl-1.4-pentadien-3-ones has been elucidated by spectroscopic methods.     

2-氨基-6-环丙胺基-9H-嘌呤的合成

氰乙酸乙酯经亚硝化、与盐酸胍在乙醇钠存在下缩合闭环、Pd/C催化还原得2,4,5-三氨基-6-羟基嘧啶,与甲酸环合得鸟嘌呤,再经乙酰化、氯化、与环丙胺缩合得到抗病毒药阿巴卡韦中间体2-氨基-6-环丙胺基-9H-嘌呤,总收率约39%。