A method for enzymatically synthesizing cefprozil
A technology of cefprozil and enzymatic synthesis, which is applied in the field of medicine, can solve the problems of high cost and large pollution, and achieve the effect of convenient addition of raw materials, high purity, and suitable for industrial production
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Embodiment 1
[0026] Add 30g 7-APCA, 27g D-p-hydroxyphenylglycine methyl ester in a 500mL three-necked flask, add 300mL purified water, 24g penicillin acylase for synthesis, control the temperature at 18~22°C, stir the reaction, and measure 7 by HPLC after 3 hours. -APCA residues should be less than 1.5mg / mL. After passing the test, a 100-mesh sieve is used to separate the penicillin acylase and cefprozil crude product mixture. The cefprozil crude product mixture is filtered to obtain the cefprozil crude product and the filtrate. Wash and remove the penicillin acylase to obtain the enzyme reaction mother liquor, add the obtained enzyme reaction mother liquor and cefprozil crude product into a 2000mL four-neck flask, control the temperature at 5~10°C, add hydrochloric acid solution dropwise until the solution is clear, pH=0.4~0.6, Add 1400mL DMF, stir, adjust the pH value with ammonia water, add seed crystals, grow the crystals until the pH value is 5.8~6.2, control the crystal growth tempera...
Embodiment 2
[0029] Add 30g of 7-APCA, 28g of D-p-hydroxyphenylglycine ethyl ester in a 500mL three-necked flask, add 300mL of purified water, 36g of penicillin acylase for synthesis, control the temperature at 15~20°C, stir the reaction, and measure 7 by HPLC after 3 hours. -APCA residues should be less than 1.5mg / mL. After passing the test, use a 120-mesh screen to separate to obtain a mixture of penicillin acylase and cefprozil crude product. The crude product mixture of cefprozil is filtered to obtain crude cefprozil and filtrate. Wash and remove the penicillin acylase to obtain the enzyme reaction mother liquor, add the obtained mother liquor and crude cefprozil into a 2000mL four-neck flask, control the temperature at 5~10℃, add hydrochloric acid solution dropwise until the solution is clear, pH=0.4~0.6, add 1300mL DMF, stirring, adjusting the pH value with ammonia water, adding seed crystals, growing the crystals until the pH value is 6.0~6.4, controlling the crystal growth temperatu...
Embodiment 3
[0032] The reaction conditions are basically the same as those in Example 1, except that the penicillin acylase recovered in Example 1 is used to adjust the pH to 7.0-7.8 with ammonia water, and the reaction temperature is controlled at 15-25°C for activation. The molar yield of the cefprozil finished product of the present embodiment is 78%, the purity is 99.5%, and the appearance is white.
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