First characterization at atomic resolution of the C-activating groups in a peptide synthesis acid chloride,acid azide and carboxylic-carboxylic mixed anhydride*

The X-ray diffraction structures of three N^α-protected, C^α-activated MeAib derivatives are reported. They are Tos-MeAib-Cl, Tos-MeAib-N₃ and Tos-MeAib-O-Piv. The geometry and conformation of these classical carboxyl activating groups, which have been characterized at atomic resolution for the first time, are discussed.     

人血凝结因子Xa发色底物的合成研究

利用混合酸酐法和活泼酯法及廉价的试剂较方便地合成了人血凝结因子Xa的一种发色底物。     

4-去乙酰化长春碱氨基酸衍生物的合成

目的:合成4-去乙酰化长春碱氨基酸衍生物,为长春碱靶向前药的合成奠定基础。方法:氨基酸N端采用苄氧羰基(Z)保护,利用混合酸酐法合成(4-去乙酰化长春碱)-氨基酸-Z,然后催化氢化得到(4-去乙酰化长春碱)-氨基酸衍生物。结果:采用新方法合成4-去乙酰化长春碱氨基酸衍生物,结构经质谱和1H-NMR确证。结论:本实验所采用的方法通用性强,优化了反应条件,反应步骤缩短,产率高,产物后处理简便,降低了实验成本。     

Synthesis of glutathione analogues with modified ionizable groups for the study of enzyme: ligand interactions

The syntheses and analyses of GSSG analogues with modified ionizable groups are described. Using the mixed anhydride method, three symmetrical and three asymmetrical peptide analogues were obtained in moderate overall yields. The products were analyzed by HPLC, ¹H-NMR, thin-layer electrophoresis, and amino acid analysis. They were used to study enzyme: ligand interactions in glutathione reductase.     

Synthesis of dipeptide 4-nitroanilides containing non-proteinogenic amino acids

A series of tert-butyloxycarbonyl amino acid 4-nitroanilides, including N-alkylated amino acids and (R)- thiazolidine-4-carboxylic acid, (S)-oxazolidine-4-carboxylic acid. (4S,5S)-5-methyloxazolidine-4-carboxylic acid, (4S,5R)-5-methyloxazolidine-4-carboxylic acid, (S)-azetidine-2-carboxylic acid, (S)-pipecolic acid and (S)-3,4-dehydroproline, were prepared conveniently by the isocyanate method or the mixed anhydride procedure. The resulting amino acid 4-nitroanilides were extended to corresponding dipeptide 4-nitroanilides with tert-butyloxycarbonyl-(S)-alanine. In the case of sterically hindered amino acid 4-nitroanilides the mixed anhydride procedure with diphenylphosphinyl chloride was successful.     

生色底物连续速率法测定圆斑蝰蛇凝血因子X激活剂的活性

目的:采用生色底物连续速率法测定凝血因子X激活剂的酶学活性。方法:将凝血因子X激活剂与凝血因子X及生色底物同时加入反应体系,以1 min为间隔时间,连续监测凝血因子Xa的生色底物Suc-Ile-Gly(γP ip)G ly-Arg-pNA在405 nm波长下的吸收值变化。通过吸收值对时间平方作图所得直线的斜率,对凝血因子X激活剂的浓度进行线性回归从而测得供试品的活性。结果:该方法的线性范围为0.45~1.20 u.mL-1,凝血因子X激活剂制剂与溶液的板间精密度(n=4)分别为6.2%及6.8%,板内精密度(n=3)分别为1.5%和1.8%。结论:本方法进行凝血因子X激活剂的活性测定,快速、准确、重现性良好。     

A facile preparation of (2,4,6‐14C)‐cyanuric acid under solvent‐free conditions

(2,4,6‐¹⁴C)‐Cyanuric acid was prepared from ¹⁴C‐urea by the heterocyclization of the latter in the presence of ammonium chloride. This procedure involves solvent‐free fusing of the reactants in a vacuum sealed glass tube. The product was purified by ion‐exchange column chromatography using Sephadex SE C‐25. A radiochemical yield of 60.5% was obtained based on ¹⁴C‐urea and the product had a specific activity of 19.06 mCi/mmol. Copyright © 2002 John Wiley & Sons, Ltd.     

肝病用氨基酸制剂在临床营养支持中的应用

肝功能不全时代谢异常,血浆氨基酸谱发生改变,Fisher比值下降,出现不同程度营养不良,肝病用氨基酸制剂配合肠内营养(EN)或肠外营养(PN)支持治疗,对营养的改善和肝功能的转归都有着重要的临床意义。该文就肝病用氨基酸制剂在临床营养支持中的应用做一简要阐述。     

A facile preparation method of a PFC-containing nano-sized emulsion for theranostics of solid tumors

Theranostics means a therapy conducted in a diagnosis-guided manner. For theranostics of solid tumors by means of ultrasound, we designed a nano-sized emulsion containing perfluoropentane (PFC5). This emulsion can be delivered into tumor tissues through the tumor vasculatures owing to its nano-size, and the emulsion is transformed into a micron-sized bubble upon sonication through phase transition of PFC5. The micron-sized bubbles can more efficiently absorb ultrasonic energy for better diagnostic images and can exhibit more efficient ultrasound-driven therapeutic effects than nano-sized bubbles. For more efficient tumor delivery, smaller size is preferable, yet the preparation of a smaller emulsion is technically more difficult. In this paper, we used a bath-type sonicator to successfully obtain small PFC5-containing emulsions in a diameter of ca. 200nm. Additionally, we prepared these small emulsions at 40°C, which is above the boiling temperature of PFC5. Accordingly, we succeeded in obtaining very small nano-emulsions for theranostics through a very facile method.     

发色底物法测定注射用降纤酶中类凝血酶的含量

目的建立发色底物法测定注射用降纤酶类凝血酶的方法。方法以Be-Phe-Val-Arg-PNA为发色底物,检测波长405nm。结果降纤酶在2～10单位/mL范围内呈良好的线性关系,r=0.9993(n=5)。结论本法简便,准确,专属性强,适用于产品的质量控制。     

Preparation of N-9-fluorenylmethoxycarbonylamino acid chlorides from mixed anhydrides by the action of hydrogen chloride1

N-9-Fluorenylmethoxycarbonyl- (Fmoc) amino-acid chlorides have been prepared by reaction of hydrogen chloride on purified mixed Fmoc-amino acid-monoalkyl carbonic acid anhydrides in dichloromethane. The products partially undergo subsequent conversion to the corresponding esters due to the presence of the liberated alcohol, the extent depending on the nature of the alkyl group. Esterification occurred to 5–20% when the alkyl group was isopropyl. Anhydrides of monoisopropenyl carbonic acid which liberate acetone instead of an alcohol gave products uncontaminated with ester. The three components in a reaction mixture could be determined as the reaction progressed by normal phase high-performance liquid chromatography of aliquots, which had been freed of excess hydrogen chloride, on a μPorasil (underivatized silica) column using tert-butanol-hexane (1.5:98.5) as solvent.     

效应面法优化盐酸昂丹司琼微球的制备工艺

目的：优化盐酸昂丹司琼聚乳酸乙醇酸嵌段共聚物（PLGA）微球的处方工艺。方法：o／o型乳化溶剂挥发法制备微球，采用小复合设计安排实验，考察盐酸昂丹司琼和PLGA的重量比（X1）、PLGA在内相中的浓度（X2）以及正己烷加入的时间（X3）对微球性质的影响。微球性质的评价指标是包封率（Y1）、载药量（Y2）、粒径（Y3）、体外释曲曲线零级方程拟合的相关系数（Y4）和16d的累积释放度（Y5）。根据最佳数学模型绘制效应面图，通过效应面法优化制备工艺。结果：最优工艺：X1为1：10，X2为32％，X3为65min。按照优化工艺制备的微球的包封率为50．69％，载药量4．6l％，粒径为58μm，体外释药曲线符合零级释放（r=0．99），16d的累积释放度约为91％。优化工艺的预测值和实洲值比较接近。结论：采用效应面法完成了盐酸昂丹司琼微球的多目标优化。     

银杏酚的简易合成

目的用简易方法合成银杏酚,为银杏酚的制备寻找新的途径。方法以3,5-二甲氧基溴苯为原料,经金属化、偶联、脱甲基化反应制得银杏酚。结果成功地合成了银杏酚,总收率为63%,其结构经核磁共振氢谱及元素分析确证。结论本法合成步骤短,反应条件温和,收率较高。     

一种饱和褐藻胶寡糖的制备方法

目的报道一种饱和褐藻胶寡糖的制备方法。方法以褐藻胶为原料,用酸水解法降解,在pH2.85处分级获得均聚古罗糖醛酸片段(PG)和均聚甘露糖醛酸片段(PM),分别在稀盐酸中水解(PG:pH3.8,120℃,3h;PM:pH4,120℃,4h)。水解物经凝胶渗透色谱法分离,获得寡糖组分,反复纯化后,获得系列褐藻胶寡糖。用红外光谱(IR)、核磁共振谱(NMR)、质谱(MS)等方法分析了寡糖的结构。结果褐藻胶经酸水解法降解,分离纯化后获得古罗糖醛酸寡糖二糖到六糖和甘露糖醛酸寡糖二糖到六糖,结构分析表明寡糖保持了原褐藻胶大分子的结构特征。结论本研究为褐藻胶低分子寡糖的制备提供了一种有效、简便的方法。     

萃取-显色法快速测定莪术油脂质体包封率

目的：建立快速测定莪术油脂质体（ZTO-L）包封率的方法。方法：采用香草醛硫酸显色法,在波长520nm处测定脂质体中莪术醇的含量,利用石油醚萃取法分离ZTO-L与游离药物,考察石油醚用量与脂质体和药物回收率的关系;并与葡聚糖凝胶柱色谱分离法和透析法进行比较。结果：莪术醇浓度在0.8～6.0μg·ml-1线性关系良好（r=0.997）。莪术油中莪术醇的百分含量为70.37%。石油醚萃取法对空白脂质体的回收率为99.34%,对莪术醇回收率为98.77%,用该法所测脂质体平均包封率为70.78%。透析法不适合用于分离ZTO-L与游离药物。结论：萃取-显色法可快速准确地测定ZTO-L的包封率,且不受脂质体粒径、ZETA电位的限制。     

甘露醇-旋光法测定鞣柳硼三酸散中硼酸的含量

目的建立旋光法测定鞣柳硼三酸散中硼酸的含量。方法以低浓度明胶溶液提取制剂中硼酸,利用甘露醇结合硼酸形成具有旋光性复合物,并建立鞣柳硼三酸散中硼酸的含量测定方法。结果硼酸浓度在5～20 g.L-1的浓度范围内与旋光度线性关系良好(r=0.999 2),方法的平均回收率为99.98%,RSD为1.3%。结论旋光法测定鞣柳硼三酸散中硼酸的含量,操作简便、快速,结果准确,重现性好。     

用HPLC法和氨基酸分析仪测定多维氨基酸片中18种氨基酸

目的：RP-HPLC法和氨基酸分析仪（amino acid analyzer，AAA）法测定氨基酸含量的比较。方法：采用Agilent高效液相色谱系统和日立835-50氨基酸分析仪测定多维氨基酸片中18种氨基酸的含量。RP-HPLC法采用C18柱和邻苯二甲醛柱前衍生化进行，AAA法采用离子交换色谱柱和茚三酮柱后衍生化进行。结果：HPLC法和AAA法的变异系数分别〈1．5％和3％，最小检测量分别为3pmol和30pmol。HPLC法的测定值与AAA的测定值有相关性。两种测定方法的平均相对偏差为5．74％（0．24％～9．60％）。结论：两种方法都可用于测定氨基酸，但测定结果存在差异。     

A facile synthesis of deuterium labeled 2,2‐dimethyl‐[2H6]‐succinic acid and its anhydride

Deuterium labeled 2,2‐dimethyl‐[²H₆]‐succinic anhydride by a sequence of reactions involving Knoevenagel condensation of [²H₆]‐acetone with ethyl cyanoacetate in the presence of piperidine, Michael addition of cyanide, HCl hydrolysis, simultaneous decarboxylation, and subsequent dehydration using acetic anhydride in an overall yield of 34.23% based on [²H₆]‐acetone utilized in the reaction is reported. The title compounds were characterized and confirmed spectroscopically by Fourier transform infrared, ¹H‐NMR, and Mass. The chemical purity as determined by HPLC was 99%. To the best of our knowledge, the synthesis of these specifically deuterium labeled compounds has not been reported so far.     

11-脱氧甘草次酸的制备

目的制备11-脱氧甘草次酸。方法采用改进的克莱门森反应还原甘草次酸的11位羰基。结果制备了11-脱氧甘草次酸,并通过IR、NMR等手段对其结构进行了鉴定。结论改进的克莱门森还原法制备11-脱氧甘草次酸收率较高,对环境友好,而且简便。