(S)-3-苯基-2-氨基丙硫醇盐酸盐的合成

以L 苯丙氨酸为原料经还原反应得到氨基醇,用Boc基团进行氨基保护后得到(S) 3 苯基 2 叔丁氧羰基氨基 1 丙醇,甲磺酰化后与硫代乙酸钾在DMF中反应得到(S) 3 苯基 2 叔丁氧羰基氨基 1 丙硫醇乙酸酯,再分别脱除乙酰基,氨基保护基后得到(S) 3 苯基 2 氨基丙硫醇盐酸盐.并用元素分析、红外光谱、核磁共振等手段对中间体和目标化合物进行了表征.     

三步法合成高封端率端氨基聚乳酸

叔丁氧羰基碳酸酐((Boc)2O)和氨基丙醇反应合成叔丁氧羰基氨基丙醇(Boc-氨基丙醇),以此为引发剂在辛酸亚锡的催化下,引发L-丙交酯开环聚合合成叔丁氧羰基氨基封端聚乳酸(BocNH-PLLA),叔丁氧羰基(Boc)经三氟乙酸处理脱除后得到端氨基聚乳酸(PLLA-NH2).以PLLA-NH2为大分子引发剂,引发ω-苄氧羰基L-赖氨酸-N-羧酸酐(ω-Z-L-Lysine-NCA)开环聚合,合成聚L-乳酸-聚ω-苄氧羰基L-赖氨酸两嵌段共聚物(P(LLA-LLz)).采用红外光谱(FT-IR)、核磁共振氢谱(1H-NMR)、凝胶渗透色谱(GPC)对聚合物结构进行了表征.结果表明:PLLA-NH2端基亲核性明显提高,可引发ω-Z-L-Lysine-NCA开环聚合制备嵌段共聚物,PLLA-NH2的合成方法简便,氨基封端率高,其分子量和单体与引发剂的摩尔比具有良好的线性关系.     

合成宾达利的新方法

以邻氨基苯乙酮(2)为原料,经过连续的重氮化-还原-缩合反应序列制得3-甲基-1H-吲唑(3);3经(Boc)2O保护亚氨基后以NBS进行甲基溴代反应制得1-叔丁氧羰基-3-溴甲基-1H-吲唑(5);5与2-羟基异丁酸乙酯缩合得醚2-(1-叔丁氧羰基-1H-吲唑-3-基)甲氧基-2-甲基丙酸乙酯(6);6经HCl/乙酸乙酯溶液脱Boc保护制得关键中间体7;在叔丁醇钾存在下,7与溴苄缩合并水解合成了MCP-1抑制剂宾达利,总收率37.3%,其结构经1H NMR,13C NMR和MS确证。     

沙库必曲中间体(R)-2-(叔丁氧羰基氨基)-3-(联苯-4-基)丙醇的合成

采用D-酪氨酸衍生物为原料,与苯磺酰氯反应制得叔丁氧羰基保护的D-苯丙氨醇苯磺酸酯,经还原,再在5 mol% N-杂环卡宾(NHC)钯催化剂(IMes)Pd(Py)Cl作用下与苯硼酸经过Suzuki-Miyaura偶联反应得到沙库必曲重要中间体(R)-2-(叔丁氧羰基氨基)-3-(联苯-4-基)丙醇,总产率大于57%,ee值大于99%。     

手性γ-氨基酸:5-羟基-3-氨基环己基甲酸的不对称合成

以光学纯的(1S,5S)-5-叔丁氧羰基氨基-3-环己烯基甲酸为原料,经立体选择性地碘代内酯化、脱碘、醇解、水解、酯化5步反应首次合成了两个光学纯的γ-氨基酸衍生物——(1R,3S,5R)-5-羟基-3-叔丁氧羰基氨基环己基甲酸甲酯(总收率36.7%)和(1R,3S,5R)-5-羟基-3-叔丁氧羰基氨基环己基甲酸苄酯(总收率35.2%),其结构经1H NMR,13C NMR,IR和ESI-HR-MS确证。     

S-[2-(叔丁氧羰基氨基)乙基]-3-苯基丙酸硫酯类化合物脱除Boc保护基的反应研究

报道了取代苯丙酸类化合物1a～1d与N-叔丁氧羰基-L-半胱氨酸甲酯(2)在双(2-氧代-3-噁唑烷基)次磷酰氯(BOP-C1)作用下,以79%～92%收率得到缩合产物S-[2-(叔丁氧羰基氨基)乙基]-3-苯基丙酸硫酯类化合物3a～3d;3a～3d在三氟乙酸(TFA)作用下脱除Boc保护基时,结果不仅得到了正常的脱保护基产物4a～4d,还生成了2-取代噻唑啉类化合物5a～5d,研究表明5a～5d是由4a～4d分子内脱水环合而成.通过优化三氟乙酸用量、反应温度以及反应时间等条件,能够以较高收率分别得到4a～4d和5a～5d(收率85%～91%和86%～89%).而S-[2-(叔丁氧羰基氨基)乙基]-3-苯基丙烯酸硫酯类化合物3e～3f由于双键结构,在三氟乙酸作用下仅生成脱除Boc保护基产物4e～4f.该反应的研究为2-取代噻唑啉类化合物的合成提供了一种简便有效的方法.     

ω-苯基-(2S)-N-叔丁氧羰基氨基酸乙酯的制备

格氏试剂和N-叔丁氧羰基焦谷氨酸乙酯反应生成中间体ω-苯基-δ-氧代-(2S)-N-叔丁氧羰基氨基酸乙酯, 分别用对甲基苯磺酰肼和醋酸硼氢化钠结合的一锅法还原或Pd/C催化氢化还原中间体得到ω-苯基-(2S)-N-叔丁氧羰基氨基酸乙酯.     

N-叔丁氧羰基-3-羟基-1-金刚烷基甘氨酸的合成

以金刚烷甲酸(1)为起始原料,经过酰化,取代,脱羧三步反应一锅法制得金刚烷甲基酮(2),然后氧化甲基得到1-金刚烷基乙醛酸(3),将3与盐酸羟氨反应得到1-金刚烷乙醛酸肟(4),还原4并用BOC酸酐保护氨基得到N-叔丁氧羰基-1-金刚烷基甘氨酸(5),最后经高锰酸钾氧化得到DPP-IV抑制剂沙格列汀中间体N-叔丁氧羰基-3-羟基-1-金刚烷基甘氨酸(6),总收率28%。     

(S)-2-氨基-1,1-二苯基-1-丙醇的合成和外消旋Droxidopa前体的拆分

(S)-2-氨基-1,1-二苯基-1-丙醇是一种合成多种手性助剂的重要中间体,也用于外消旋屈昔多巴前体化合物的拆分。从价廉易得的L-丙氨酸出发,通过四步反应制得,总收率55.6%L-丙氨酸经甲酯化,苄氧羰基保护制得的L-2-苄羰基氨基丙酸甲酯与苯基溴化镁反应制得(S)-2-苄氧羰基氨基-1,1-二苯基-1-丙醇。是在5%Pd/C催化加氢下脱除苄氧羰基得到标题化合物。该制备方法涉及的中间体及目标化合物易于纯化,总收率高且重现性好。我们用制得的氨基醇能成功地拆分外消旋苏式屈昔多巴前体化合物3-3,4-二苄氧苯基)-N-苄氧羰基丙氨酸。     

基于树枝状分子及功能化金纳米粒子的电化学免疫传感器检测污泥中大肠杆菌

利用树枝状分子-金纳米粒子复合物修饰电极和金纳米粒子标记物构建电化学免疫传感器,用于污泥中大肠杆菌的检测.首先在玻碳电极表面电聚合对氨基苯甲酸,通过共价作用结合第Ⅳ代氨基末端的树枝状分子(G4-PAMAM),并在其内部载入金纳米粒子,制备修饰电极(GCE/p-ABA/PAMAM (AuNPs)),用于固定大肠杆菌.采用硫堇作为电活性物质包被金纳米粒子,用于标记二抗制备金纳米粒子标记物(Ab2-Au-Th).通过抗原-抗体之间的特异性识别作用,将一抗、金纳米粒子标记物依次修饰在电极表面,用差分脉冲伏安法测定硫堇产生的电流信号,实现对大肠杆菌的检测.在优化的实验条件下,响应电流与大肠杆菌浓度的对数在1.0×102～1.0×106 cfu/mL范围内呈线性关系,检出限为70 cfu/mL(S/N=3).利用本方法检测污水处理厂的不同污泥样品中的大肠杆菌,回收率为89.4％～ 105.8％.     

基于血红蛋白/纳米金/二氧化锆-壳聚糖修饰的过氧化氢生物传感器

将二氧化锆(ZrO2)分散于壳聚糖(CS)中得到稳定的CS-ZrO2复合物,制备了Hb/nano-Au/CS-ZrO2/Au过氧化氢生物传感器。 用循环伏安法和计时电流法考察该修饰电极的电化学特性,发现该修饰电极对过氧化氢(H2O2)的还原有良好的电催化作用。 实验结果表明,该传感器对H2O2的线性响应范围为3.9×10-6～1.8×10-3 mol/L,线性相关系数R=0.9956,检测下限为5.6×10-7 mol/L(S/N=3),并具有选择性高、线性范围宽和响应快等优点。     

对乙酰氨基酚在纳米金/十二烷基苯磺酸钠修饰电极上的电化学行为研究

基于电化学沉积法制备了纳米金/十二烷基苯磺酸钠修饰玻碳电极(Nano-Au/SDBS/GCE),并采用扫描电子显微镜、X-射线光电子能谱和电化学方法进行表征。研究了对乙酰氨基酚在Nano-Au/SDBS/GCE上的伏安行为,结果表明,对乙酰氨基酚由在裸玻碳电极上的不可逆氧化过程变为准可逆过程,氧化峰峰电位由0.60 V负移至0.50 V,且在0.42 V处产生一个新的还原峰,表明nano-Au/SDBS膜能催化对乙酰氨基酚的电化学反应。在优化条件下,氧化峰峰电流与对乙酰氨基酚浓度在1.0×10-6mol/L～9.0×10-6mol.L–1和1.0×10-5～1.0×10-4mol.L–1间有良好的线性关系,检出限为8.0×10-7mol.L–1(S/N=3)。     

基于二氧化锆和碳纳米管协同作用的过氧化氢生物传感器

过氧化氢作为一种重要的化工产品在纺织行业、化工行业、造纸工业、环保行业、电子行业、食品卫生行业及其他领域得到广泛的应用~([1]).     

An amperometric hydrogen peroxide biosensor based on immobilizing horseradish peroxidase to a nano-Au monolayer supported by sol-gel derived carbon ceramic electrode

A novel strategy for fabricating horseradish peroxidase (HRP)-based H(2)O(2) sensor has been developed by combining the merits of carbon sol-gel supporting matrix and nano-scaled particulate gold (nano-Au) mediator. The thiol functional group-derived carbon ceramic electrode (CCE) was first constructed using (3-mercaptopropyl) trimethoxy silane as sol-gel monomer. Then, the stable nano-Au monolayer was obtained through covalent linkage between nano-Au and thiol group on the surface of CCE. The experimental results showed that nano-Au monolayer formed not only could steadily immobilize HRP but also efficiently retain its bioactivity. Hydrogen peroxide was detected with the aid of hydroquinone mediator to transfer electrons between the electrode and HRP. The process parameters for the fabrication of the enzyme electrode and various experimental variables such as the operating potential, mediator concentration and pH of background electrolyte were explored for optimum analytical performance of the enzyme electrode. The biosensor had a fast response of less than 8 s with linear range of 1.22 x 10(-5) to 1.10 x 10(-3)mol l(-1) and a detection limit of 6.1 x 10(-6)mol l(-1). The sensitivity of the sensor for H(2)O(2) was 0.29 A l mol(-1) cm(-2). The activation energy for enzyme reaction was calculated to be 10.1 kJ mol(-1). The enzyme electrode retained 75% of its initial activity after 5 weeks storage in phosphate buffer at pH 7.     

以天青Ⅰ为介体的纳米金颗粒增强的葡萄糖传感器

采用层层自组装的方法和异种电荷互相吸引的原理,将Nafion修饰在金电极上固载带正电荷的天青Ⅰ,并利用天青Ⅰ中的氨基固载纳米金,再通过纳米金将酶固定在金电极表面,制成了葡萄糖传感器.采用循环伏安法和交流阻抗法,研究了金电极表面组装各层之后的电化学特征,以及电极对葡萄糖的电化学催化作用. 结果表明,天青Ⅰ不仅可以固定酶和纳米金,而且还可以在酶和电极之间有效地传递电子.在优化的实验条件下,该传感器对葡萄糖响应的线性范围为5.1×10-6 ~4.0×10-3 mol/L,检出限(S/N=3)为1.0 μmol/L.该生物传感器显示出较好的稳定性和抗干扰能力,将其用于人体血清中葡萄糖的测定,结果令人满意.     

Selective determination of dopamine in the presence of high concentration of ascorbic acid using nano-Au self-assembly glassy carbon electrode

The cysteamine (CA) was bound onto surface of the pretreated glassy carbon electrode (GC) with cyclic voltammetry (CV). Gold nanoparticles were self-assembled to the electrode binding with cysteamine via strong AuS covalent bond to fabricate the nano-Au self-assembled modified electrode (nano-Au/CA/GC). The modified electrode was characterized with cyclic voltammetric and ac impedance methods. The electrochemical behavior of dopamine (DA) on the modified electrode was investigated with cyclic voltammetry and differential pulse voltammetry (DPV). A well-defined redox peaks of DA on the nano-Au/CA/GC electrode were obtained at E_pa = 0.175 V and E_pc = 0.146 V (vs. SCE), respectively. The peak current of DA is linear with the concentration of DA in the range of 1.0 × 10⁻⁸ mol L⁻¹ to 2.5 × 10⁻⁵ mol L⁻¹, with the correlation coefficient of 0.998. The detection limit is 4.0 × 10⁻⁹ mol L⁻¹ (S/N = 3). The modified electrode exhibited an excellent reproducibility, sensibility and stability for determination of DA in the presence of high concentration AA, and can be applied to determinate dopamine injection, with satisfied result.     

A high-sensitive amperometric hydrogen peroxide biosensor based on the immobilization of hemoglobin on gold colloid/L-cysteine/gold colloid/nanoparticles Pt-chitosan composite film-modified platinum disk electrode

A hemoglobin (Hb)/gold colloid (nano-Au)/L-cysteine (L-cys)/nano-Au/nanoparticles Pt (nano-Pt)-chitosan (CHIT) composite film-modified platinum disk electrode (abbreviated to modified electrode) has been prepared to construct a biosensor for determination of H(2)O(2). The electrochemical characteristics of the biosensor were studied by cyclic voltammetry and chronoamperometry. The modified process was characterized by electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The morphologies of different composite film were investigated with scanning electron microscopy (SEM) and the element of composite film was investigated with X-ray photoelectron spectroscopy (XPS). Analytical parameters such as pH and temperature were also studied. The linear range for the determination of H(2)O(2) is 1.4 x 10(-7) to 6.6 x 10(-3)mol/L with a detection limit of 4.5 x 10(-8)mol/L (S/N=3). The sensor achieved 95% of the steady-state current within 10s. The sensor exhibited high sensitivity (17.62 microA/(mmol L)), selectivity and stability. The method is applied to the determination of H(2)O(2) with satisfactory results.     

One-step construction of an electrode modified with electrodeposited Au/SiO2 nanoparticles, and its application to the determination of NADH and ethanol

A new electrode was developed by one-step potentiostatic electrodeposition (at ?2.0 V for 20 s) of Au/SiO₂ nanoparticles on a glassy carbon electrode. The resulting electrode (nano-Au/SiO₂/GCE) was characterized by scanning electronic microscopy, X-ray photoelectron spectroscopy and electrochemical techniques. The electrochemical behavior of dihydronicotinamide adenine dinucleotide (NADH) at the nano-Au/SiO₂/GCE were thoroughly investigated. Compared to the unmodified electrode, the overpotential decreased by about 300 mV, and the current response significantly increased. These changes indicated that the modified electrode showed excellent catalytic activity in the oxidation of NADH. A linear relationship was obtained in the NADH concentration range from 1.0?×?10^?6 to 1.0?×?10^?4 mol?L^?1. In addition, amperometric sensing of ethanol at the nano-Au/SiO₂/GCE in combination with alcohol dehydrogenase and nicotinamide adenine dinucleotide was successfully demonstrated. A wide linear response was also found for ethanol in the range from 5.0?×?10^?5 to 1.0?×?10^?3 mol?L^?1 and 1.0?×?10^?3 to 1.0?×?10^?2 mol?L^?1, respectively. The method was successfully applied to determine ethanol in beer and biological samples.     

亚硝酸根在纳米金修饰玻碳电极上的电催化氧化行为及其测定

采用直接电化学沉积法制备出纳米金修饰玻碳电极,研究了其对亚硝酸根的电催化氧化作用。结果表明,亚硝酸根在该修饰电极上于0.8 V处出现了一个良好的氧化峰。在最优实验条件下,亚硝酸根的峰电流与其浓度在2×10-6～2×10-3mol/L范围内呈一定的线性关系,检出限为6.0×10-7(S/N=3),提出了用循环伏安法测定亚硝酸根的方法。纳米金修饰电极用于东莞自来水水样中亚硝酸根的测定,回收率在98.1%～101.4%之间。对比本方法,用分光光度法对东莞自来水样中亚硝酸根进行了测定,结果满意。