酶法合成头孢羟氨苄工艺研究

Study on the process of enzymatic synthesis of cefadroxil

对酶法合成头孢羟氨苄的工艺条件进行优化,以7-氨基-3-脱乙酰氧基头孢烷酸(7-amino-3-desacetoxy cephalosporanic acid,7-ADCA)为母核,对羟基苯甘氨酸甲酯(D-hydroxy phenylglycine methyl ester,D-HPGM)为酰基供体,利用青霉素G酰化酶(PGA)在水相体系中酶促合成头孢羟氨苄(cefadroxil)。该实验以温度、p H值、侧链与母核的摩尔比、投酶量、母核浓度和酶的种类等6个因素对头孢羟氨苄合成工艺条件进行优化,转化反应过程中按时取样,利用高效液相色谱仪对母核进行定量分析,追踪母核7-ADCA转化率,直至终止反应。实验结果表明,在温度为20℃、p H6.5、摩尔比1.2:1、投酶量20g、母核浓度13%、采用新A4酶的工艺条件下,母核的转化率可达到99.47%。

To optimize the process conditions of enzymatic synthesis of cefadroxil, make 7-amino-3-desacetoxy cephalosporanic acid （7-ADCA） as the parent nucleus, and D-hydroxy phenylglycine methyl ester （D-HPGM） as the acyl donor, and use penicillin G acylase （PGA） in aqueous enzymatic synthesis of cefadroxil. In this experment, optimize six factors of cefadroxil synthesis conditions including the temperature, pH value, the molar ratio of side chain and the parent nucleus, investment amount of enzyme, parent nucleus concentration and species of enzyme, and sample on time during conversion reaction process to use the liquid chromatograph to analyze the parent nucleus quantitatively and track the conversion rate of the parent nucleus 7-ADCA until the termination of the reaction. The experimental results show that the conversion rate of the parent nucleus can be reached 99.47% at the temperature of 20℃, pH6.5 and at the molar ratio of 1.2：1, using investment amount of enzyme 20g, parent nucleus concentration of 13% and new enzyme A4.