硝酸布康唑的合成

目的合成硝酸布康唑。方法以4-氯苄基氯为起始原料,经Grignard反应、缩合、氯化、缩合、成盐等5步反应制得目标化合物。结果目标化合物的熔点、红外光谱均与文献报道一致,总收率为37.9%,纯度为99.6%（HPLC法）。结论本工艺操作简单,成本较低,适合工业化生产。     

HPLC法测定硝酸异康唑软膏中的硝酸异康唑的含量及有关物质

目的：建立高效液相色谱法，测定硝酸异康唑软膏中的硝酸异康唑的含量及有关物质。方法：用ZORBAX Extend C18（250mm×4．6mm，5μm）色谱柱，2％醋酸铵溶液-甲醇-乙腈（270：375：355）为流动相，检测波K为235nm。结果：硝酸异康唑与硝酸益康唑的分离度大于5．0及检出灵敏度完全达到要求，最小检出量为0．02μg。浓度在40～250μg·mL^-1。内线性关系良好（r=1．0000，n=6）。平均回收率为101．1％，RSD为1．1％。结论：本方法准确、简便、快速，能有效控制硝酸异康唑软膏的质量。     

3-溴-5-乙酰基异(口恶)唑的合成

目的：本合成方法是以合成3-溴-5-乙酰基异噁唑为目的。方法用乙醛酸和丙炔酸乙酯为原料，经5步反应合成3-溴-5-乙酰基异噁唑。结果总收率为(19．9％)，反应条件温和，原料价廉易得，适于规模化生产。     

抗真菌新药硝酸异康唑的研究进展

摘 要 硝酸异康唑是一种广谱抗真菌药,具有高效的抗真菌和抗革兰阳性菌活性,对表浅部真菌病疗效出色。文中对硝酸异康唑的作用机制、药物动力学、药物相互作用、临床评价和安全性等进行综述。     

硝酸依柏康唑的合成工艺改进

目的改进硝酸依柏康唑的合成方法。方法以3,5-二氯溴苄为起始原料经Wittig反应、氢化、水解、环合4步反应得到关键中间体2,4-二氯-10,11-二氢-5H-二苯并[a,d]环庚烯-5-酮,该中间体经还原、氯代、氮烃化、成盐4步反应合成硝酸依柏康唑。结果与结论目标化合物的结构经质谱、核磁共振氢谱确证。与原工艺路线相比,改进后的路线反应步骤短、操作简单、条件温和,易于工业化生产,总收率为26%(以3,5-二氯溴苄计)。     

硝酸布康唑栓微生物限度检查方法适用性试验研究

目的 对硝酸布康唑栓微生物限度检查方法适用性试验研究分析.方法 该试验通过硝酸布康唑栓限度检查的方法,观察分析硝酸布康唑酸对真菌和革兰阳性细菌的抑制作用.结果 结果显示,依据硝酸布康唑栓白色念珠菌和金黄色葡萄球菌总数计数.结论 该试验中硝酸布康唑栓对真菌和细菌具有较强的抑菌作用,采用中和法和薄膜过滤法可去除抑菌的作用.     

3-氨甲酰基-和3-氨基-5-甲基异噁唑的合成工艺研究

本文对磺胺甲(口恶)唑的两个中间体3-氨甲酰基-5-甲基异(口恶)唑(1)和3-氨基-5-甲基异(口恶)唑(2)的合成工艺进行了一些研究。国内采用以草酸二乙酯为起始原料、中间产物不加分离的一锅合成工艺合成1,经过工艺改进,收率不断提高。80年代初报道用5-甲基异(口恶)唑-3-甲酸酯的醇溶液氨解得1的收     

6-(1-溴乙基)-4-氯-5-氟嘧啶合成新方法

以氟乙酸乙酯为起始原料,改进抗真菌药物伏立康唑中间体6-(1-溴乙基)-4-氯-5-氟嘧啶的合成方法.该方法简化了生产工艺,降低了反应成本,反应条件温和,适合工业化生产,总收率为41.7%.     

硝酸舍他康唑泡腾胶囊的制备工艺和含量测定

目的研究硝酸舍他康唑泡腾胶囊的制备工艺及含量测定。方法确定处方的组成,制备泡腾胶囊,并用紫外分光光度法测定硝酸舍他康唑的含量。结果紫外分光光度法测定硝酸舍他康唑含量的标准曲线为A=0．0075p＋0．0096（r=0．9997）,在质量浓度10～90mg·L^-1内吸光度与质量浓度之间的线性关系良好。结论该泡腾胶囊的制备方法简单,用紫外分光光度法测定含量,方法可靠。     

美洛昔康合成工艺改进

目的改进关洛昔康的合成工艺，提高美洛昔康的收率。方法通过工业丙醇为原料合成2-氨基-5-甲基噻唑，提高了收率。美洛昔康的合成采用二甲基甲酰胺和二甲苯混合作溶剂，减少溶剂用量。结果收率从40．7％提高到52．5%。结论美洛昔康的改进工艺提高了工业化生产的批生产量。     

Recent advances in automated solid-phase carbohydrate synthesis: from screening to vaccines

The past year has witnessed significant advances in a new technology for the synthesis of complex carbohydrates. Solid-phase methods have been applied to the construction of previously inaccessible carbohydrates. Furthermore, the application of automated solid-phase carbohydrate synthesis is promising. New methods for the synthesis of carbohydrates and potential applications are described in this review.     

6个小分子海洋药物的全合成方法

骨架新颖、活性独特的海洋天然产物是药物先导化合物的重要来源,但由于海洋样品采集困难、一些高活性天然产物在海洋生物体中含量低微,往往难以获取足够量的化合物进行后续药物的深入研究,成为海洋小分子药物研究的瓶颈之一。现代有机合成尤其是海洋天然产物全合成的迅猛发展,为获取复杂小分子海洋活性天然产物提供了一个重要手段。探究复杂小分子海洋天然产物合成的新策略和新方法,建立高效、高选择性的规模化制备技术,是国际海洋药物研究的热点。本文就6个上市的小分子海洋药物的全合成研究作一概述,重点阐述有机合成对于成药分子规模化制备的途径。     

连续流动化学在药物合成中的应用

连续流动化学是近十多年来发展的新技术。因连续流动化学具有安全性极高、传热传质速度快、自动化程度高和可在线监测及纯化等优点,促进了其在有机合成反应中的快速发展。在放热量较大、需高温高压和环境污染大的反应中的优势尤为明显。本文综述了近年来连续流动化学技术在药物合成中的应用,进一步说明了它的优点和重要意义,也展示了连续流动化学技术在药物合成中的广阔前景。     

4-三氟甲氧基苯胺的合成及应用

本文介绍了含氟中间体的理化性质、反应机理、最新的应用及科研发展走向.以4-三氟甲氧基苯胺作为含氟中间体的代表化合物进行合成工艺路线的研究以及实际研发应用,并简单介绍一种新的合成方法,以对氨基苯酚、三氟溴甲烷为原料合成对三氟甲氧基苯胺,拓展了对三氟甲氧基苯胺的合成思路,为学者做了详细的总结与归纳,以便更简洁、方便地了解含氟化合物及其下游产品4-三氟甲氧基苯胺,也为其工艺的优化和新工艺研究的摸索开辟道路.     

Chemical protein synthesis methods in drug discovery

The applicability of chemical protein synthesis over the last five years has been greatly expanded by significant increases in the size (up to 600 amino acids) and variety of accessible proteins, including new classes of proteins such as phosphoproteins, glycoproteins and integral membrane proteins. Chemical protein synthesis has also produced novel high-throughput screening and biosensor technology, and exciting lead compounds for the generation of powerful synthetic protein pharmaceuticals.     

芽孢杆菌中天然脂肽类抗生素的合成及作用机制研究进展

摘要：抗生素的发现为治疗细菌感染带来了突破性进展,但随之而来的抗生素耐药性问题也愈发严峻。在减缓抗生素耐药性进展的同时,发现新型抗生素的需求也愈发强烈。天然抗生素是新型抗生素的潜在选择,而芽孢杆菌能够产生多种具有广谱抑菌活性的细菌脂肽,包括polymyxins、surfactins、iturins、fengycins等,具有巨大的研究和开发潜力。本文综述了芽孢杆菌产生的一系列脂肽类抗生素的特征、合成及作用机制,充分展现了芽孢杆菌脂肽的应用潜力。未来可利用基因组测序技术挖掘新型脂肽类抗生素合成通路,利用基因工程及分子生物学技术提高产量,运用化学合成和化学修饰进行改良,促进芽孢杆菌中脂肽类抗生素的开发利用。     

Nucleotide deoxysugars: essential tools for the glycosylation engineering of novel bioactive compounds

The irreversible spread of new resistance mechanisms against existing therapeutical antibiotics has led to the development of technologies and strategies for the glycosylation engineering of novel antibiotics. Amino-, C-branched and O-methylated 6-deoxyhexoses play a favourite role in the biosynthesis of clinically important antibiotics like tylosin, erythromycin or oleandomycin and are essential for the antibiotic activity. They are transferred onto the aglycon by glycosyltransferases using dTDP-activated deoxyhexoses. The in vitro biochemical characterization of the biosynthetic enzymes and the glycosyltransferases are, however, hampered due to the poor synthetic access to dTDP-activated deoxysugars and their biosynthetic intermediates. The overcoming of the poor availability of dTDP-activated sugars was the target of several researchers to fulfil their distinct aims with these sugars which were mostly involved in the synthesis of different biological active compounds. Several completely different strategies were used in the past years to improve the availability of dTDP-activated deoxysugars, varying from complete enzymatic synthesis via syntheses using reaction technology for yield optimization to full organic synthesis or shortcuts like the decomposition of commercially available antibiotics and later chemical activation of the sugar moieties. This review gives a survey of the synthesis of dTDP-activated sugars by chemical and chemoenzymatic approaches and discusses the promiscuity of glycosyltransferases to evaluate the chances for applying them for the production of new bioactive compounds. It summarizes the most important enzymes in the field of synthesis using biosynthetic pathway enzymes and describes solutions for occurring challenges during application. Finally, this review will give a survey about the availability of dTDP-activated sugars in sufficient scale and will also point at important sugars which are still bottlenecks and difficult to synthesize and therefore should become a target for enhanced research efforts.     

The application of microwave irradiation as new convenient synthetic procedure in drug discovery

Heterocyclic compounds hold a special place among pharmaceutically important natural and synthetic materials. The remarkable ability of heterocyclic nuclei to serve both as biomimetics and reactive pharmacophores has largely contributed to their unique value as traditional key elements of numerous drugs. In both lead identification and lead optimization processes there is an acute need for new organic small molecules. Traditional methods of organic synthesis are orders of magnitude too slow to satisfy the demand for these compounds. The fields of combinatorial and automated medicinal chemistry have been developed to meet the increasing requirement of new compounds for drug discovery, within these fields, speed is of the essence. The efficiency of microwave flash-heating chemistry in dramatically reducing reaction times (reduced from days and hours to minutes and seconds) has recently been proven in several different fields of organic chemistry. We believe that the time saved by using focused microwaves is potentially important in traditional organic synthesis but could be of even greater importance in high-speed combinatorial and medicinal chemistry. In this review, it is impossible to cover all significant developments in the area of microwave-assisted organic synthesis (MAOS). Rather, outlines the basic principles behind the technology and summarizes the areas in which microwave technology has made an impact, to date. Specific attention is given to application of microwave irradiation in liquid systems, and in the solid state as well of several representative biologically interesting nuclei. In addition we report some of the most recently disclosed applications in combinatorial chemistry.     

Solid-phase and combinatorial synthesis in beta-lactam chemistry.

Combinatorial chemistry has became a core technology for the rapid development of novel lead compounds in the pharmaceutical industry and for the optimization of therapeutic efficacy. The effort to prepare libraries of compounds by combinatorial chemistry has led to an unprecedented growth in solid phase organic synthesis (SPOS), particularly for the preparation of non-oligomeric small molecules. In this context, the clinically valuable b-lactam compounds are very attractive targets for research using these new techniques. In recent years, b-lactam compounds have been recognized not only as unique antibacterial agents but also as potent enzyme inhibitors, drug delivery agents, and versatile synthetic intermediates. This review gives a comprehensive up-date for the application of solid-phase and combinatorial synthesis to b-lactam compounds.     

Some interactions of natural and synthetic anionic polymers with biologically active substances

Anionic polymers are nowadays extensively used in drug form technology, especially in drug delivery and drug targeting. Development of proper drug and macromolecular excipient composition allows controlled drug delivery in the term of the drug concentration in blood or other tissues, and in the term of the action-time. Between anionic polymers most frequently carbopols, eudragits, alginates and pectins are used. Application of anionic polymers in drug form technology is an up to date problem. According to new synthesis methods and new anionic polymers, new drug delivery systems would be researched. Most selective and safe devices should be developed, concerning biodegradation aspects.