降血脂药物中L-肉毒碱的高效液相色谱法测定

建立了高效液相色谱法测定降血脂药物中L-肉毒碱含量的简便方法.采用Kromasil NH2柱(250mm×4.6mm,5μm),以乙腈∶KH2PO4溶液(6.81g/L,用NaOH调至pH=4.7)=65∶35为流动相,流速为1.0mL/min,检测波长为205nm.结果显示,在用高效液相色谱测试L-肉毒碱(0.4g/L)时,其注射体积在0.5~10L范围内与色谱峰面积呈良好的线性关系,相关系数为0.999 9,回收率为99.53%,RSD为0.31%.该方法操作简便、快速、有良好的准确度,可作为降血脂药物中L-肉毒碱含量的测定.     

4-羟基-2-吡啶酮类化合物的合成研究进展

4-羟基-2-吡啶酮是天然生物碱结构母核,同时也是一类重要的医药中间体,该类衍生物具有抗真菌、抗菌和抗肿瘤等多种生物活性.因此,其合成得到了广泛的研究和关注.综述了近年来4-羟基-2-吡啶酮类化合物的合成方法及其研究进展.     

1-甲基-4-硝基-5-氯咪唑的合成新工艺研究

1-甲基-4-硝基-5-氯咪唑是合成免疫抑制剂硫唑嘌呤(Azathioprine)的中间体.硫唑嘌呤可抑制人体内淋巴细胞,减少狼疮病人的免疫复合物在肾脏的沉积,抑制局部炎症.同时用于治疗类风湿关节炎、各种血管炎、多发性肌炎皮肌炎及系统性红斑狼疮等.     

6-烷氧基-7-乙基-4-羟基-3-喹啉羧酸乙酯的合成及抗球虫活性研究

本文设计并合成了2个新的6-烷氧基-7-乙基-4-羟基-3-喹啉羧酸乙酯化合物.所有化合物的结构均经HRMS,1H NMR,IR和元素分析所证实.对2个化合物进行了抗球虫活性实验,结果表明,化合物6-正十四烷氧基-7-乙基-4-羟基-3-喹啉羧酸乙酯具有抗球虫效果,并有可能作为抗球虫药物使用.目标物制备方法具有合成路线短、产率高、原料易得和总生产成本低的优点.     

电氧化合成2-吡啶甲酸

以2-甲基吡啶为原料,用电化学方法合成了2-吡啶甲酸.研究了反应温度、硫酸浓度、反应物2-甲基吡啶浓度和阳极电位对选择性和电流效率的影响.结果表明,在最佳反应条件下,以电化学方法合成2-吡啶甲酸的选择性高达95.3%,电流效率可达到45.3%.     

几种姜黄素类1,4-戊二烯-3-酮衍生物的合成及结构表征

以芳香醛和酮为原料,合成了3类姜黄素类1,5-二芳基-1,4-戊二烯-3-酮衍生物:1,5-二噻吩基-1,4-戊二烯-3-酮(Ⅰ)、1,5-二苯基-1,4-戊二烯-3-酮类(Ⅱ)和1,5-二呋喃基-1,4-戊二烯-3-酮(Ⅲ);利用元素分析、红外光谱、核磁共振谱(1 H NMR及13 C NMR)分析了产物的组成和结构,初步探讨了其反应条件和反应机理.结果表明,以无水乙醇为溶剂、8%的NaOH溶液为催化剂,反应温度为30⁵0℃时,反应产率较高.     

6-氯哒嗪-3-甲酸甲酯的合成

以乙酰丙酸乙酯为起始原料,经过环合、溴代、消除、重铬酸钾氧化、酯化、POCl3氯代6步反应合成6-氯哒嗪-3-甲酸甲酯,目标化合物总收率42%,本方法操作简单,成本低廉,分离纯化容易,收率高,为6-氯哒嗪-3-甲酸甲酯的规模化合成奠定了基础.     

N-甲基-4-羟基-5-苯基-2-吡啶酮的合成

以丙二酸和二氯亚砜为起始原料,经氯代、环合、催化氢化及烷基化反应合成了新化合物——N-甲基-5-苯基-4-羟基-2-吡啶酮,总收率38.7％,其结构经1H NMR,IR和EI-MS表征.     

2-芳基-2-吗啉醇的合成

醇胺分别与2-溴-4′-甲氧基苯乙酮、2-溴-3′-氯苯丙酮、2-溴-4′-苄氧基苯基丙酮、2-溴-4′-苄氧基苯戊酮、6-甲氧基-2-溴乙酰基萘和6-甲氧基-2-(2-溴丙酰基)萘反应,合成相应的2-芳基-2-吗啉醇(产率80.7%～97.5%)及其盐酸盐.其结构经1H NMR,IR,MS确证.     

2,4-二氯-5-异丙氧基苯胺的合成

1 前言 2,4-二氯-5-异丙氧基苯胺是重要的染料、医药和农药中间体,特别是合成1,2,4,5- 四取代苯类含氮杂环除草剂如口恶草酮、2-[2,4-二氯-5 -(1-甲基乙氧基)苯基]-4-(2-氟乙基)-1,2,4-三嗪-3,5(2H,4H)-二酮等.该中间体合成未见国内文献报道.专利WO 8600072中报道路线是采用间氨基苯酚经酰化、氯化、水解、醚化制得产品(见方程1).     

The Effects of Streptozotocin-Induced Diabetes and Insulin Treatment on Carnitine Biosynthesis and Renal Excretion

Carnitine insufficiency is reported in type 1 diabetes mellitus. To determine whether this is accompanied by defects in biosynthesis and/or renal uptake, liver and kidney were obtained from male Sprague-Dawley rats with streptozotocin-induced diabetes. Diabetic rats exhibited the metabolic consequences of type 1 diabetes, including hypoinsulinemia, hyperglycemia, and increased urine output. Systemic hypocarnitinemia, expressed as free carnitine levels, was evident in the plasma, liver, and kidney of diabetic rats. Compared to control rats, the low free carnitine in the plasma of diabetic rats was accompanied by decreased expression of γ-butyrobetaine hydroxylase in liver and kidney, suggesting impaired carnitine biosynthesis. Expression of organic cation transporter-2 in kidney was also reduced, indicating impaired renal reabsorption, and confirmed by the presence of elevated levels of free carnitine in the urine of diabetic rats. Insulin treatment of diabetic rats reversed the plasma hypocarnitinemia, increased the free carnitine content in both kidney and liver, and prevented urinary losses of free carnitine. This was associated with increased expression of γ-butyrobetaine hydroxylase and organic cation transporter-2. The results of our study indicate that type 1 diabetes induced with streptozotocin disrupts carnitine biosynthesis and renal uptake mechanisms, leading to carnitine insufficiency. These aberrations in carnitine homeostasis are prevented with daily insulin treatment.     

Separation of ADAM derivatives of carnitine and acyl-carnitines by capillary electrophoresis

 The separation of carnitine, acetylcarnitine and palmitoylcarnitine as ADAM (9-anthryldiazo-methane) derivatives was performed using capillary electrophoresis. A buffer system with 90% methanol and various amounts of phosphoric acid and micelle forming SDS was optimized with respect to the best resolution of the carnitine derivatives. A detection limit of 10 μmol/l or 32 ng carnitine was determined by laser induced fluorescence detection. Under optimized conditions low carnitine contents in acylcarnitine standards have been determined. Received: 30 May 1996/Accepted: 17 June 1996     

Development of a CE‐MS2 method for the enantiomeric separation of L/D‐carnitine: Application to the analysis of infant formulas

A new chiral analytical method based on CE‐MS is proposed for the identification and simultaneous quantification of D /L ‐carnitine in infant formulas. Previous derivatization of carnitine with FMOC enabled the optimization of the chiral separation using CE with UV detection. An optimization of electrospray‐MS parameters using a partial filling of the non‐volatile chiral selector (succinyl‐γ‐CD) was performed. A selective fragmentation using MS² experiments with an ion trap analyser was carried out to confirm the identity of D /L ‐carnitine according to the current legislation. Satisfactory results were obtained in terms of linearity, precision, and accuracy. Interestingly, the CE‐MS² method developed allowed a sensitivity enhancement with respect to UV detection of 100‐fold, obtaining an LOD of 100 ng/g for D ‐carnitine. The determination of L ‐carnitine and its enantiomeric purity in 14 infant formulas supplemented with carnitine was successfully achieved, sample preparation only requiring an ultrafiltration with centrifugal filter devices to retain the components with the highest molecular weights.