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酶法合成頭孢羥氨芐工藝研究

發(fā)布時間:2019-06-09 17:47
【摘要】:對酶法合成頭孢羥氨芐的工藝條件進行優(yōu)化,以7-氨基-3-脫乙酰氧基頭孢烷酸(7-amino-3-desacetoxy cephalosporanic acid,7-ADCA)為母核,對羥基苯甘氨酸甲酯(D-hydroxy phenylglycine methyl ester,D-HPGM)為酰基供體,利用青霉素G;(PGA)在水相體系中酶促合成頭孢羥氨芐(cefadroxil)。該實驗以溫度、p H值、側鏈與母核的摩爾比、投酶量、母核濃度和酶的種類等6個因素對頭孢羥氨芐合成工藝條件進行優(yōu)化,轉化反應過程中按時取樣,利用高效液相色譜儀對母核進行定量分析,追蹤母核7-ADCA轉化率,直至終止反應。實驗結果表明,在溫度為20℃、p H6.5、摩爾比1.2:1、投酶量20g、母核濃度13%、采用新A4酶的工藝條件下,母核的轉化率可達到99.47%。
[Abstract]:The technological conditions for the synthesis of Cefadroxil by enzyme method were optimized. 7-amino-3-deacetyloxycephalosporic acid (7-amino-3-desacetoxy cephalosporanic acid,7-ADCA) was used as the mother core and p-hydroxyphenylglycine methyl ester (D-hydroxy phenylglycine methyl ester,) was used as the mother core of Cefadroxil (Cefadroxil). D-HPGM) as acyl donor, Cefadroxil (cefadroxil). Was synthesized by penicillin G acylase (PGA) in aqueous system. In this experiment, the synthesis conditions of Cefadroxil were optimized by six factors: temperature, pH value, molar ratio of side chain to mother nucleus, amount of enzyme, concentration of mother nucleus and type of enzyme, and sampling was carried out on time in the process of conversion. The mother nucleus was quantitatively analyzed by high performance liquid chromatography (HPLC) to track the conversion of 7-ADCA in the mother nucleus until the reaction was terminated. The experimental results show that the conversion of mother nucleus can reach 99.47% when the temperature is 20 鈩,

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