固定化青霉素酰化酶在DMSO-水介质中催化合成头孢氨苄

Semi-Synthesis of Cephalexin in DMSO-Water Medium by Immobilized Penicillin G Acylase

与传统的化学方法相比较 ,酶法合成头孢菌素工艺具有明显优点 ,通过酶的固定化与非水相酶催化技术相结合为提高产率找到了简捷的途径。实验以 7 氨基 3 脱乙酰氧基头孢烷酸 (7 amino 3 deactoxycephalosporanic,7 ADCA)为母核 ,苯甘氨酸甲酯盐酸盐 (D phenylglycinemethylesterchlorohydrate ,PGME)为酰基供体 ,在二甲亚砜 (DMSO) 水共溶剂体系中 ,采用聚丙烯腈纤维固定化青霉素酰化酶 (penicillinacylaseEC3 .5 .1.11,PA)催化合成头孢氨苄 (Cephalexin)。发现DMSO浓度、反应温度、pH、底物浓度等对转化率均有影响。在 2 5℃ ,pH6 .5 ,40 %DMSO 水体系中 ,7 ADCA、PGME浓度分别为 85mmol/L ,12 8mmol/L时 ,7 ADCA转化率达 90 %。在 15次反复合成Cephalexin期间 ,转化率保持 90

Semi synthesis of cephalexin from 7 aminodecetoxicephalosporanic acid (7 ADCA) and D( ) phenylglycine methyl (PGME) using polyacrylnitrile(PAN) immobilized penicillin G acylase in the DMSO water cosolvent is investigated. Finally, some promising results were obtained as follows: (1)Synthesis yield was markedly increased in comparing with that in the aqueous medium, (2)Immobilized enzyme maintained higher percentage of catalytic activity in aqueous organic cosolvent, (3) High concentration of substrate could be used. The cosolvent system, DMSO water media was estabilished on the basis of selection from difficult polar solvents. Effects of a variety of conditions, such as solvent content, substrate concentration, pH, temperature on synthesis of cephalexin were investigated. Under optimal conditions, IPGA in 40% DMSO aqueous medium converted 85mmol/L 7 ADCA and 128mmol/L PGME into cephalexin at pH6.5, 25℃. During 15 batches of semi synthesis, the IPGA kept the conversion rate over 90%.