An improved enzymatic method for preparing amoxicillin
A technology for the preparation of amoxicillin and enzymatic method, applied in the field of preparation of amoxicillin, can solve the problems of low bulk density, difficulty in packaging, and high poisoning of operators
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Embodiment 1
[0091] Material preparation:
[0092] 6-APA 12g; D-p-hydroxyphenylglycine methyl ester hydrochloride 15.6g; penicillin G acylase 2.2KU / L; 3mol / l ammonia 8ml; acetone 60ml (90% concentration); 6mol / l hydrochloric acid 11ml; 6mol / l ammonia water: 9.5ml; purified water 500ml.
[0093] making process:
[0094] Add 240ml of purified water into a 1000ml beaker, add 12g of 6-APA while stirring, then add dropwise 3mol / l ammonia water to adjust the pH to 7.5, keep the temperature at 15°C, 6-APA is completely dissolved, and the amount of 3mol / l ammonia water is 5ml; add to the beaker Add D-p-hydroxyphenylglycine methyl ester hydrochloride; then add penicillin G acylase to start the reaction; keep the reaction system at a constant temperature of 22°C, add ammonia water to control the pH=6.25, and use 3ml of 3mol / l ammonia water; after 1 hour of reaction , taking samples at regular intervals and measuring the 6-APA conversion rate (mg / ml) by HPLC: 23.17 in the first hour; 18.11 in the s...
Embodiment 2
[0096] Material preparation:
[0097] 6-APA 12g; D-p-hydroxyphenylglycine methyl ester hydrochloride 16.8g; penicillin G acylase 2.2KU / L; 3mol / l ammonia 9ml; acetone 60ml (98% concentration); 6mol / l hydrochloric acid 12ml; 6mol / l ammonia water 10ml; purified water: 500ml
[0098] making process:
[0099] 240ml of purified water was added to a 1000ml beaker, and 12g of 6-APA was added while stirring. Add 3 mol / l ammonia water dropwise, when T=15°C and pH=7.5, 6-APA is completely dissolved, and the dosage of 3 mol / l ammonia water is 5ml. Add D-p-hydroxyphenylglycine methyl ester hydrochloride to the beaker. Add synthetase and start the reaction. Keep the reaction system at a constant temperature of 22°C, add ammonia water to control the pH=6.25, and use 4ml of 3mol / l ammonia water. After reacting for 1 hour, sample 6-APA at regular intervals to measure the conversion rate (mg / ml): 1st hour: 22.89; 2nd hour: 17.55; 3rd hour: 8.68; 4th hour: 6.71; 5th hour: 4.33; stop the re...
Embodiment 3
[0102] Material preparation:
[0103] 6-APA 12g; D-hydroxyphenylglycine methyl ester hydrochloride 19.2g; penicillin G acylase 2.2KU / L; 3mol / l ammonia 10.5ml; methanol 60ml (85% concentration); 6mol / L hydrochloric acid 12.5 ml; 6mol / L ammonia water 11ml; purified water 500ml.
[0104] making process:
[0105] Add 240ml of purified water into a 1000ml beaker, then add 12g of 6-APA, and stir at the same time; add dropwise 3mol / l ammonia water, when T=15°C, pH=7.5, 6-APA is completely dissolved, and the dosage of 3mol / l ammonia water is 6ml; Add D-p-hydroxyphenylglycine methyl ester hydrochloride into the beaker; add synthetase to start the reaction; keep the reaction system at a constant temperature of 22°C, add ammonia water to control the pH=6.25, and use 4.5ml of 3mol / l ammonia water; - APA conversion rate (mg / ml): 23.01 in the 1st hour; 17.61 in the 2nd hour; 8.54 in the 3rd hour; 6.83 in the 4th hour; 4.35 in the 5th hour; stop the reaction; Crude.
[0106] In a 500ml b...
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