Green method of enzymatic synthesis of cefaclor

Abstract

The invention relates to a green method of enzymatic synthesis of cefaclor. The method includes the steps of: (S1) adding a parent nucleus 7-ACCA into a buffer liquid; (S2) under the pH of 5-8, adding a D-p-hydroxyphenylglycinate derivative or a salt thereof and / or D-p-hydroxyphenylglycine amide, and immobilized cefaclor synthesis enzyme, and performing a reaction for 1-3 h at 5-30 DEG C under the pH value of 6.2-7.8; after a certain reaction time, adding a seed crystal to perform crystallization, and when the reaction is finished, separating a reaction liquid and the immobilized cefaclor synthesis enzyme to obtain a cefaclor coarse product; and (S3) acid-hydrolyzing and dissolve-clarifying the coarse product, filtering and re-crystallizing the product to prepare the cefaclor. The enzymatic synthesis method, compared with a conventional chemical synthesis method, is simple in operation, is low in cost, reduces synthetic period, improves production efficiency and total yield, has strong controllability and satisfies industrial production.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a method for synthesizing cefaclor by a green enzymatic method. Background technique [0002] Cefaclor (Cefaclor) is the second generation of oral cephalosporin derivatives. It is a new drug reported by Lilly Company in 1975. It was approved by FDA in 1979 and launched in the United States in 1982. In 1985, it replaced cephalexin as the world's first best-selling drug. Antibiotics, whose patent expired in 1993. In February 1994, Cefaclor was introduced to the Chinese market under the trade name "Xindaro". Cefaclor has a strong killing effect on a variety of Gram-positive and Gram-negative bacteria. It has good activity against pneumococcus, hemolytic streptococcus, Neisseria gonorrhoeae and anaerobic bacteria. It is mainly used clinically for respiratory tract infections, such as pharyngitis, pneumonia, urinary tract infections, such as pyelonephritis, cystitis, a...

AI Technical Summary

Problems solved by technology

These two methods have long reaction steps, so the reactive sites of the starting materials and intermediates need to be protected first, the yield is not high, a large amount of organic solvents are used, a lot of waste liquid is produced, and the environmental protection pressure is high.

At the same time, an ultra-low temperature refrigeration unit or liquid nitrogen is required to meet the low temperature reaction requirements, which consumes a lot of energy, requires extremely high moisture content for solvents and starting materials, and requires harsh reaction conditions. Harsh process conditions lead to relatively high production risks.