Preparation method of broad-spectrum long-acting penicillin antibiotic ticarcillin sodium

Abstract

The invention provides a ticarcillin sodium preparation method which has mild reaction conditions, less side reactions, less steps, and high controllability, and the method comprises the following steps: (1) allowing 3-thienylmalonic acid to react with N-hydroxysuccinimide in an organic solvent with the catalysis of DCC and DMAP to obtain an intermediate 1, performing separation and purification by column chromatography; (2) dissolving the intermediate 1 in dichloromethane, adding 6-APA and an alkali to react so as to obtain ticarcillin; (3) allowing ticarcillin to react with a salt forming agent to obtain ticarcillin sodium.

Description

technical field [0001] The invention relates to a preparation method of ticarcillin sodium, a spectrum long-acting penicillin antibiotic, and belongs to the technical field of medicines. [0002] Background technique [0003] Penicillin is extracted from the culture fluid of Penicillium fungus, and there are 7 kinds in total, among which Penicillin G (Penicillin G) has the strongest effect and the highest yield, and has clinical application value. Penicillin G has been used clinically for more than half a century. It is characterized by strong antibacterial effect and is used for various cocci and Gram-positive bacteria. Cause drug resistance and narrow antibacterial spectrum. [0004] [0005] [0006] Penicillin G [0007] [0008] 6-APA [0009] In order to solve the defects of penicillin, many semi-synthetic penicillins have been developed by using 6-aminopenicillanic acid (6-APA) obtained from penicillin fermentation broth as raw materials, including spectrum...

AI Technical Summary

Problems solved by technology

[0012] At present, there are multiple synthetic routes for obtaining ticarcillin sodium by connecting side chains with 6-APA. Generally speaking, most of them are carrying out condensation reaction after carboxyl or amino protection of 6-APA or 3-thiophene malonate, and then reacting The product is hydrolyzed and salified to obtain the final product. Usually, after protecting the amino and carboxyl groups of 6-APA with trimethylchlorosilane, it is condensed with 3-thienylmalonyl chloride to obtain the intermediate N-trimethylsilane-6- [α-Chlorocarbonyl-2-(3-thienyl)-acetamide]-trimethylsilicone penicillate, after hydrolysis, salted with sodium 2-ethylhexanoate, after purification with ethyl acetate To obtain the final product, this method needs to protect the group first and then hydrolyze the reaction product. The steps are cumbersome, and the hydrolysis reaction is difficult to carry out and difficult to control.

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