他克林的合成

靛红和盐酸羟胺反应制得靛红-3-肟,在环丁砜中经氧化锌催化裂解得到的邻氨基苄腈,和环己酮在无水氯化锌及TEBA作用下于140℃反应0.5 h,制得阿尔兹海默病治疗药他克林,总收率约56%.     

RuCl3催化下-锅法合成α-氨基腈

各种醛、一级胺或二级胺与氰化三甲基硅烷于无水乙腈中，在20mol％无水RuCl3催化下室温反应，得相应的α-氨基腈。该法简单高效，11例收率69％～87％。     

磷酸奥司米韦的合成

（-）-莽草酸经酯化、丙酮保护、甲磺酰化、缩酮交换、还原开环和闭环反应得中间体环氧化物,之后经叠氮开环氧、staudinger反应合成氮丙啶中间体,然后再用叠氮开氮丙啶环、氨基乙酰化、还原叠氮基后与磷酸成盐得到抗流感病毒药磷酸奥司米韦.重点优化了丙酮保护、氮丙啶形成和叠氮还原3个步骤.避免了使用价格较贵的试剂,以及严格无水且易燃易爆的苛刻反应条件,总收率约为14%.     

头孢唑肟钠生产工艺及条件的研究

目的:对头孢唑肟钠生产过程进行研究。方法:以粗品7-氨基-3-烷基头孢烷酸和AE活性酯为原料合成头孢唑肟酸,再与无水碳酸钠反应制得头孢唑肟钠;同时研究反应时间、乙醇用量和滴加时间、无水碳酸钠的用量以及pH值对产品质量的影响。结果:反应过程完全可以实现,合成头孢唑肟钠的适宜工艺参数为反应时间1.5h,乙醇滴加速度400mL.h-1,反应温度30℃以下,乙醇与头孢唑肟酸用量比30mL∶1g,无水碳酸钠与头孢唑肟酸的质量比0.15∶1.00,溶液pH值6.9±0.1。结论:该工艺切实可行,为头孢唑肟钠工业化生产提供了可靠的依据。     

替代重氮甲烷的羧酸甲酯化方法

羧酸在无水 DMF中 ,加入 Li OH· H2 O,于室温反应 0 .5 h,接着加入 Me2 SO4,加热至回流 ,保持 3 h,经处理得相应的甲酯。酯化过程中芳环上的羟基、氨基和酰胺基等敏感基因不受影响。 2 6例收率 72 %～ 1 0 0 %。本法反应条件温和 ,所用试剂价廉毒性小替代重氮甲烷的羧酸甲酯化方法@庄武     

相转移催化剂及其在有机合成方面的应用

引言相转移催化是近年来逐渐发展的一种化学合成方法。1971年C.M.Starks对此曾进行了阐述:当两种反应物分别处在两种不相混的溶液中时,彼此不能反应,但当加入少量第三种物质后,由于它的作用反应即能迅速进行,这种作用即为相转移催化(Phase-Transfer Catalysis,简称PTC)。该第三种物质称为相转移催化剂(Phase-Transfer Catalyst,简称PTC)。此后由于一些反应认为必须在无水条件下,应用诸如氢化钠、氨基钠、醇钠等强碱     

多沙唑嗪、特拉唑嗪及哌唑嗪的高效合成

用4-氨基-2-氯-6,7-二甲氧基喹唑啉与无水哌嗪反应制得4-氨基-2-哌嗪基-6,7-二甲氧基喹唑啉(2).另用2-氯-4,6-二甲氧基-1,3,5-三嗪(3)和4-甲基吗啉(4)反应后加入相应的羧酸,制得的中间体7再与2反应分别制得多沙唑嗪(1a)、特拉唑嗪(1b)和哌唑嗪(1c),总收率分别为82.3％、88.0％和86.4％(以3计).     

1—（2—吡啶基）哌嗪的合成

用工业品2－氨基吡啶在Br2-HBr体系中重氮化,制得2－溴吡啶,收率73．5％;2－溴吡啶与工业无水哌秦直接反应,制得1－（2－吡啶基）哌嗪,收率60％。     

低毒性的抗癌剂9位取代的喜树碱

自然界存在着具有强的抗癌活性的9-甲氧基喜树碱,但因含量很低未作深入研究。本专利以喜树碱为起始原料经硝化、还原、酰化或烷基化得到9位酰氨基或9位烷基胺基取代的喜树碱衍生物。经重氮化反应使氨基转化为重氮盐再与甲醇反应便得9位甲氧基喜树碱。将喜树碱溶于浓硫酸中,在冷却搅拌下,于室温慢慢滴加数倍量的浓硝酸,室温反应24至72h,将反应液倒入水中,以氯仿提取,氯仿层用无水硫酸镁干燥后移去溶剂,残渣经硅胶柱层析纯化得到收率为30％～40％     

邻乙酰胺基苯甲酸的合成

邻硝基甲苯用高锰酸钾氧化得邻硝基苯甲酸,铁粉还原得邻氨基苯甲酸,在无水碳酸钾存在下,与乙酰氯回流得邻乙酰胺基苯甲酸,总收率48.5%.     

胆酸细菌内毒素检查方法的建立

目的 建立检查不溶于水的胆酸原料中细菌内毒素的方法.方法 以无水乙醇为溶剂溶解胆酸后进行试验.结果 无水乙醇短暂处理对细菌内毒素的活性无明显影响,1.25％的乙醇和0.35 g/L的胆酸溶液对鲎试剂和细菌内毒素的凝集反应无明显干扰.结论 胆酸经无水乙醇溶解后采用凝胶法进行细菌内毒素检查是可行的.     

Synthesis of 2-(aryl)-5-(arylidene)-4-thiazolidinone derivatives with potential analgesic and anti-inflammatory activity

A series of novel N-[5-(arylidene)-2-(aryl)-4-oxo-thiazolidin-3-yl]-4-biphenylcarboxamide derivatives was synthesized and evaluated for analgesic and anti-inflammatory activity. In this study, biphenyl-4-carboxylic acid hydrazide was converted to the corresponding aryl hydrazones using aryl aldehydes in the presence of catalytic amount of glacial acetic acid. The aryl hydrazones on reaction with thioglycolic acid in the presence of anhydrous zinc chloride yielded N-[2-(aryl)-4-oxo-thiazolidin-3-yl]-4-biphenylcarboxamide which further on reaction with aromatic aldehydes in the presence of anhydrous sodium acetate and glacial acetic acid furnished the title compounds. All compound exhibited anti-inflammatory activity at the dose 10?mg/kg. The structures of all these newly synthesized compounds were confirmed by their elemental analyses (C, H, N) and spectral data (IR and ¹H NMR).     

对《中国药典》2015版附录无水磷酸氢二钠氯化物鉴别试验方法的改进

目的 ： 改进《中国药典》2015版药用辅料无水磷酸氢二钠氯化物鉴别试验方法,避免黄色悬浮物干扰比色结果。 方法：加入硝酸的量必须大于2.3mL或无水磷酸氢二钠称样量不能超过3.25g,避免滴加硝酸银溶液时与磷酸根反应生成黄色的磷酸银而干扰鉴别试验现象的观察。结果：加大硝酸的量或减少称样量,可以有效防止磷酸氢根电离和磷酸银的形成。结论：本方法可以避免比色鉴别试验出现黄色悬浮物结果。     

USE OF THIOCYANIC ACID TO FORM 2-THIOHYDANTOINS AT THE CARBOXYL TERMINUS OF PROTEINS

The chemistry of the formation of 2-thiohydantoins on the carboxyl terminal of peptides or proteins was investigated. It was found that thiocyanic acid was much more reactive for the formation of 2-thiohydantoins than were the thiocyanate salts. The physical reasons for this observation are explained. The kinetics of the reaction of a number of proteins, and some of their fragments, with thiocyanic acid were also determined. Simple and safe procedures for the preparation of anhydrous thiocyanic acid solutions were devised. The prospective application of these procedures to sequencing from the carboxyl terminal of a polypeptide is discussed.     

超声引导下聚桂醇硬化治疗肾囊肿的效果

目的：对比和分析聚桂醇注射液与无水乙醇治疗肾囊肿的临床效果。方法选取2011年6月~2013年2月在本院确诊并治疗的肾囊肿患者60例作为研究对象,随机分为聚桂醇组和无水乙醇组,超声引导经皮肾穿,分别将聚桂醇注射液与无水乙醇溶液注入两组肾囊肿内,对比两组的疗效及不良反应发生率。结果聚桂醇组的总有效率为96.67%,高于无水乙醇组的83.33%,差异有统计学意义（P＜0.05）。聚桂醇组的不良反应发生率为16.67%,低于无水乙醇组的36.67%,差异有统计学意义（P＜0.05）。结论采用超声引导下聚桂醇注入肾囊肿的治疗效果明显优于无水乙醇,且不良反应发生率更低,其可作为一种新型、更安全、更有效的硬化剂,值得临床推广应用。     

Clarification on publications concerning the synthesis of acetylsalicylic acid

Charles Frédéric Gerhardt (1816-1856) mentioned in his Traité de chimie Organique (1854) a publication, in French (realized in 1852 but published in 1853) entitled "Researches on anhydrous organic acids" in which, was reported the reaction of sodium salicylate with acetyl chloride. He thought that the reaction product was an acid anhydride, but obtained really crude acetylsalicylic acid. Later on, but also in 1853, a publication in german, by the same author related the same experiments. Surprisingly only the second publication has been mentioned in most of the historical studies on the subject. Acetyl salicylic acid was identified and synthesised in 1859 by von Gilm by another method and the product obtained by Gerhardt was identified to it in 1869.     

一种简便的酯合成法

酯化反应是一个可逆反应,在索氏提取器中装入干燥剂除去生成的水,可使反应趋于完成,无需预先制备无水醇,操作简单,收率较高。     

大茴香酸-硫酸荧光体系测定黄芪甲苷

黄芪甲苷 (ａｓｔｒａｇａｌｏｓｉｄｅ)是中药膜荚黄芪Ａｓｔｒａｇａｌｕｓｍｅｍｂｒａｎａｃｅｕｓ (Ｆｉｓｃｈ .)Ｂｇｅ .和蒙古黄芪Ａｓｔｒａｇａｌｕｓｍｅｍｂｒａｎａｃｅｕｓ (Ｆｉｓｃｈ .)Ｂｇｅ .ｖａｒ .ｍｏｎｇｈｏｌｉｃｕｓ (Ｂｇｅ .)Ｈｓｉａｏ的主要活性成分 ,有抗炎、降压、镇痛、镇静、升高血浆中ｃＡＭＰ水平、促进小鼠再生肝ＤＮＡ的含量[1,2 ] 以及促进免疫功能等生理活性。黄芪甲苷的测定方法主要有 :紫外分光光度法[3 ,4 ] 、薄层扫描法[5,6] 和ＨＰＬＣ法[7,8] 。光度法常用香草醛在浓硫酸作用下与甲苷显色…     

马来酸桂哌齐特的合成

目的 改进马来酸桂哌齐特的合成方法。方法 以四氢吡咯为原料,与氯乙酰氯酰化得到中间体N-(2-氯乙酰基)四氢吡咯(1);以(E)-3,4,5-三甲氧基肉桂酸为原料,与特戊酰氯成混合酸酐后再与无水哌嗪进行单酰化反应制得中间体(E)-1-(3,4,5-三甲氧基)肉桂酰基哌嗪(2);中间体1与中间体2发生烃化反应制备桂哌齐特游离碱(3),3与马来酸成盐得目标化合物。结果与结论 以(E)-3,4,5-三甲氧基肉桂酸计,经3步反应合成了马来酸桂哌齐特,总收率为68.88%,其结构经1H-NMR、MS谱确证。     

Instability in Theophylline and Carbamazepine Hydrate Tablets: Cocrystal Formation Due to Release of Lattice Water

Purpose

To demonstrate two sequential solid-state reactions in intact tablets: dehydration of active pharmaceutical ingredient (API), and cocrystal formation between the anhydrous API and a second formulation component mediated by the released water. To evaluate the implication of this in situ phase transformation on the tablet dissolution behavior.

Methods

Tablets containing theophylline monohydrate (TPM) and anhydrous citric acid (CA) were stored at 40°C in sealed polyester pouches and the relative humidity in the headspace above the tablet was continuously measured. Dehydration to anhydrous theophylline (TPA) and the product appearance (TPA-CA cocrystal) were simultaneously monitored by powder X-ray diffractometry. Carbamazepine dihydrate and nicotinamide formed the second model system.

Results

The water of crystallization released by TPM dehydration was followed first by deliquescence of citric acid, evident from the headspace relative humidity (~ 68%; 40°C), and then the formation of TPA-CA cocrystal in intact tablets. The noncovalent synthesis resulted in a pronounced decrease in the dissolution rate of theophylline from the tablets. Similarly, the water released by dehydration of carbamazepine dihydrate caused the cocrystallization reaction between anhydrous carbamazepine and nicotinamide.

Conclusions

The water released by API dehydration mediated cocrystal formation in intact tablets and affected dissolution behavior.