Enzymatic synthesis process of a new cephalosporin anti-infective drug

Abstract

The invention relates to an enzymatic synthesis technology of a novel cephalo-type anti-infection drug. The technology comprises the following steps: preparing TDA hydrochloride from TDA, purifying, processing to prepare TDA sodium salt, and directly carrying out enzymatic synthesis of cefazedone sodium in a water phase under the action of immobilized penicillin acylase. The enzymatic synthesis technology has the advantages of operating step simplification, implementation of a reaction in the water phase, mild reaction conditions, few byproducts, great reduction of energy consumption and organic wastewater discharge, cost reduction, small pollution to environment, good environmental protection property, and industrialization requirement meeting; and the technology greatly improves the product yield and the product yield, the product purity is greater than 99.9%, and the total yield is greater than 90%.

Description

technical field [0001] The invention relates to the field of drug synthesis, in particular to an enzymatic synthesis process of a novel cephalosporin anti-infective drug cefazirone sodium. Background technique [0002] Cefazedone sodium (Cefazedone) belongs to the first generation of injectable cephalosporin antibiotics, and its curative effect on various Gram-positive bacteria and Gram-negative bacteria, including Staphylococcus aureus, Streptococcus, and Enterococcus, is superior to similar drugs— The drug resistance of cefazolin and cephalothin is obviously better than that of the latter. They are classic broad-spectrum antibiotics with broad antibacterial spectrum and wide clinical application. A total of 732 patients in 7 foreign countries and 35 hospitals participated in the clinical research results showed that cefzidome was effective against urinary system infection, respiratory tract infection, surgical-skin infection and gynecological infection caused by gram-posit...

AI Technical Summary

Problems solved by technology

[0011] In the above-mentioned two kinds of processing routes, the synthesis of route one mainly starts from the 7-position of 7-ACA, and route two begins to synthesize from the 3-position of 7-ACA, and route two synthesizes cefzidone yield (71.5 %) is slightly higher than route one (60%), but the weak point of route two is that the by-product of 1-methylthiadiazole-5-mercaptan and 7-ACA reaction is accompanied in the end product always, and it is difficult to Find a suitable purification method, so that its synthesis cost will increase accordingly, which is not suitable for industrial production

[0012] In the prior art method for synthesizing cefazedone sodium, there are generally low yields, poor product color grades and high industrial production costs.

The difficulty of the process leads to the high price of the preparation, which creates an economic burden on the drug users, and the use of highly polluting chemical reagents in the synthesis process causes great damage to the environment

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