甲磺酸多沙唑嗪的合成

丙烯酸乙酯经溴化,与邻苯二酚环合,哌嗪化,成盐制得中间体1-（1,4-苯并二噁烷-2-甲酰基）哌嗪盐酸盐。该中间体与2-氯-4-氨基-6,7-二甲氧基喹唑啉反应制得盐酸多沙唑嗪,再与甲磺酸反应得甲磺酸多沙唑嗪,对反应溶剂进行选择,在最优溶剂条件下,总收率为29．7％,该方法工艺简单,适用于工业化生产。     

甲磺酸帕珠沙星的合成

研究了甲磺酸帕珠沙星的合成路线及工艺。以左旋氧氟沙星的中间体（S）-9,10-二氟-3-甲基-2,3-二氢-7-氧代-7H-吡啶[1,2,3-de][1,4]苯并噁嗪-6-羧酸乙酯为起始原料,经亲核取代反应、酯水解并选择性脱羧、环合、水解、Hofmann降解、成盐,制得甲磺酸帕珠沙星,总收率49．4％。其化学结构经元素分析、^1H NMR、^13C NMR、MS得以确证。该合成路线及工艺适合工业化大生产。     

甲磺酸帕珠沙星的合成

研究氟喹诺酮类抗菌剂甲磺酸帕珠沙星的合成路线及工艺。以左旋氧氟沙星的中间体(S)-9,10-二氟-3-甲基-2,3-二氢-7-氧-7H-吡啶[1,2,3-de][1,4]苯并噁嗪-6-羧酸乙酯为起始原料,经亲核取代反应、酯水解并选择性脱羧、环合、水解、Hofrnann降解、成盐得甲磺酸帕珠沙星,总收率60.0%。其化学结构经元素分析,IR,1H NMR,13C NMR,MS得以确证。该合成路线及工艺适合工业化大生产。     

甲磺酸溴隐亭的合成研究

以α-麦角隐亭为起始原料,使用5,5-二溴巴比妥酸(DBBA)溴化,与甲磺酸成盐得到甲磺酸溴隐亭。甲磺酸溴隐亭结构通过1 HNMR、MS方法进行了确认。     

1-（1，4-苯并二噁烷-2-甲酰基）哌嗪的合成

1-(1,4-苯并二噁烷-2-甲酰基)哌嗪为甲磺酸多沙唑嗪的重要中间体,以邻苯二酚与环氧氯丙烷为原料,经环合、氧化、氯化、酰化、缩合四步反应合成了治疗高血压和前列腺增生药物甲磺酸多沙唑嗪的关键中间体1-(1,4-苯并二噁烷-2-甲酰基)哌嗪。原料廉价,易得,反应条件温和,操作方便。     

甲磺酸帕珠沙星的合成工艺改进

以左氧氟沙星的中间体--(S)-9,10-二氟-3-甲基-7-氧代-2,3-二氢-7H-吡啶[1,2,3-de][1,4]苯并噁嗪-6-羧酸乙酯为起始原料,经过与氰乙酸乙酯缩合、水解脱羧、1,2-二溴乙烷环合、水解、霍夫曼降解、成盐得到喹诺酮类抗菌药甲磺酸帕珠沙星.总收率达到43.8%,并对目标产物,进行了元素分析,IR,1H NMR,13C NMR,MS等确认.与文献报道相比,该合成工艺路线具有反应条件温和,收率较高,适合工业化生产.     

甲磺酸培氟沙星合成工艺改进

以 1 乙基 6 氟 7 氯 1,4 二氢 4 氧代喹啉 3 羧酸为原料 ,经甲哌嗪化 ,甲磺酸成盐得甲磺酸培氟沙星 ,总收率为 82 6%。     

头孢尼西钠的合成

7-氨基头孢烷酸(7-ACA)与5-巯基-1,2,3,4-四氮唑-1-甲基磺酸双钠盐(SMT-DS)在BF3作用下缩合,生成7-氨基-3-[甲磺酸基-1-H-四唑-5-基-巯甲基]-3-头孢烯4-羧酸(3).3与D-(-)-甲酰基扁桃酸酰氯在pH6.5-7.0下酰化、盐酸作用下去甲酰基成头孢尼西酸,再与N,N-二苄基乙二胺二醋酸盐(DBED)结合生成头孢尼西胺盐(5).5经酸化,成盐反应得头孢尼西钠.反应总收率为60.7%,所得产品纯度为98.7%(HPLC).     

甲磺酸多沙唑嗪未知杂质合成与结构鉴定

为了控制抗高血压药物甲磺酸多沙唑嗪产品质量,对制备甲磺酸多沙唑嗪过程中产生的一个未知杂质进行了推测与合成。HPLC、LC-MS、NMR和IR确证所合成的化合物结构即未知杂质1-(4-羟基-6,7-二甲氧基-2-喹唑啉基)-4-(1,4-苯并二恶唑-2-甲酰基)呱嗪。     

甲磺酸培氟沙星合成工艺改进

以1－乙基－6－氟－7－氯－1,4－二氢－4－氧代喹啉－3－羧酸为原料,经甲哌嗪化,甲磺酸成盐得甲磺酸培氟沙星,总收率为82.6%。     

3-氯头孢烯酸的合成

以3 羟基 7 苯乙酰基 3 头孢烯酸二苯甲酯为原料,经过氯代、酯水解、酰胺水解3步反应制备了药物头孢克洛的中间体3 氯头孢烯酸(7 氨基 3 氯 3 头孢烯 4 酸,7 ACCA),总收率73%。酶解反应中以c(NaHCO3)=1×10-3mol/L的水溶液代替常用的氨水溶液,缩短了反应时间。三氯化磷作为氯代试剂,间甲酚作为酯水解试剂,反应中采用TLC进行终控,展开剂分别为V(环己烷)∶V(乙醇)=1∶1和V(丙酮)∶V(石油醚)∶V(乙酸)=5∶5∶1。     

A new approach to catalytic hydrolysis of ester-bound biphenyl cyclooctene lignans from the fruit of Schisandra chinensis Baill by ion exchange resin

In this study, a novel approach was developed to hydrolyze ester-bound biphenyl cyclooctene lignans (EBBCL) from the fruits of Schisandra chinensis Baill into free-state biphenyl cyclooctene lignans (FSBCL) using ion exchange resin. The results of static hydrolysis tests showed that SK1B (H-type strongly acidic cation exchange resin) was the best acidic hydrolysis catalyst and 201 × 7 (OH-type strongly basic anion exchange resin) was the best basic hydrolysis catalyst. According to the underlying mechanism for hydrolytic degradation, the hydrolysis effect of basic catalyst is more obviously. The dynamic hydrolysis efficiency of 201 × 7 (146.7 ± 5.0%) was higher than that of SK1B (131.5 ± 4.7%). Compared with the purity of FSBCL (3.52 ± 0.06%) catalytic hydrolysis by traditional catalyst NaOH, the purity of FSBCL (5.85 ± 0.04%) hydrolysis by 201 × 7 resin was much higher, increased 2.94-fold under the optimization hydrolysis conditions.     

Enzymatic hydrolysis of rawhide using papain and neutrase

Rawhide split was hydrolysed separately by two proteolytic enzymes, papain and neutrase. The effects of enzymatic conditions of the hydrolysis reaction were investigated. During the first 10 min of the enzymatic hydrolysis, the yield of the hydrolysed protein increased sharply, then it slowly increased or became essentially constant due to the limited availability of the substrate. The optimum hydrolysis conditions of papain and neutrase for highest protein yield are at 70 °C, pH 6–7 and 40–50 °C, pH 6–7, respectively. The product from papain hydrolysis is a gelatin with low gel strength and viscosity, while that from neutrase hydrolysis is collagen hydrolysate with viscosity as low as water. This is considered to indicate that longer fragments of protein are obtained from papain hydrolysis than that from neutrase implying different mechanisms of papain and neutrase hydrolysis.     

Nonenzymatic hydrolysis of phosphatidylcholine prepared as liposomes and mixed micelles

Nonenzymatic hydrolysis of phosphatidylcholine was investigated at several pH ranges in liposomes and mixed micelles. Phosphatidylcholine was stable to hydrolysis for 140 hr at pH 4, 7 and 10, but slowly hydrolyzed at pH 1 with a half-time of 50 hr. We conclude that phosphatidylcholine is not significantly degraded by hydrolysis under conditions typical for liposome preparation methods.     

反胶束体系中酶法合成头孢力新的动力学

利用来自Xanthomonas citri的酰化酶由D-α-苯甘氨酸甲酯和7-ADCA合成头孢力新是典型的动力学控制合成过程,其中既有产物的合成又有产物和底物（D-α-苯甘氨酸甲酯）的水解。动力学分析表明,反应置于反胶束体系将不仅提高酶的催化速度而且提高转移酶活力对水解酶活力的选择性。利用AOT/异辛烷反胶束体系酶法合成头孢力新使水解副反应被抑制,合成途径被强化。水成为反胶束酶反应体系中重要的调节手段,它对反应速度呈“铃形”关系。     

苯醚甲环唑的水解研究

研究了苯醚甲环唑在水溶液中的水化学降解行为,结果表明:(1)苯醚甲环唑水解作用随溶液pH值的增大而增强,25℃时其在pH5、7和9的缓冲液中的水解半衰期分别为315.07、11.53和1.33d。(2)苯醚甲环唑在水体中的水解速率随温度升高而加快,其在温度为15、25、35、45℃的pH7缓冲液中的水解半衰期分别为20.81、11.53、6.80和2.14d,平均温度效应系数为2.22。苯醚甲环唑水解反应的平均活化能和活化焓分别为55.53kJ/mol和53.01kJ/mol,而苯醚甲环唑水解反应的活化熵随温度升高而降低,表现出明显的相关性,其平均活化熵为-92.45kJ/mol·k。(3)在相同的培养条件下,苯醚甲环唑在池塘水、河水和超纯水中的降解速率是不同的,其水解半衰期分别为7.31、4.47和12.49d。     

Stability of sucrose fatty acid esters under acidic and basic conditions

The stability of sucrose fatty acid monoesters toward hydrolysis under acidic and basic conditions was evaluated. Mass spectrometric analysis of hydrolysates showed that the glycosidic bond was preferentially hydrolyzed under acidic conditions, whereas the ester bond was selectively hydrolyzed under basic conditions. Under both conditions, the rate of hydrolysis depended on the pH of the solution, the concentration of sucrose monoesters, and the acylated position of the sucrose monoesters. The hydrolysis of the glycosidic bond under acidic conditions was shown to be a first-order process. The rate constants for hydrolysis at various temperatures were measured, and the activation energies were calculated from the slope of the Arrhenius plots. The lifetime of sucrose monoesters estimated from the first-order rate constant for the hydrolysis reaction revealed that the sucrose monoesters have excellent long-term stability over a pH range of 5 to 7 at room temperature.     

肉桂醛低浓度碱性水解反应体系的研究

利用等吸收点建立了紫外分光光度法定量分析肉桂醛、苯甲醛和5-苯-2,4-戊二烯醛三组分的方法,构建了组分浓度与吸光度之间的关系:CPPDA=(A338+0.038 9)/0.174 0,C肉桂醛=(A303-0.117 7CPPDA)/0.113 8,C苯甲醛=(A255-0.042 7C肉桂醛-0.020 9CPPDA)/0.059 7,研究了肉桂醛在低浓度40~60℃条件下的水解反应。结果表明,水解反应速率随温度降低趋于缓慢,反应时间越短副反应越少。采用一级反应动力学模型对动力学数据进行拟合,得到肉桂醛水解反应的活化能为56.59 kJ/mol。