Preparation method for Aspoxicillin

Abstract

The invention discloses a preparation method for Aspoxicillin. D-aspartic acid is added into a mixture liquid of sulfuryl chloride and carbinol under a low temperature of zero to prepare D-aspartic acid methyl ester hydrochloride; the obtained D-aspartic acid methyl ester hydrochloride and triethylamine are reacted in ethanol to obtain D-aspartic acid methyl ester educt; the D-aspartic acid methyl ester educt and methylamine aqueous liquid with a concentration of 40 percent are reacted in a room temperature to prepare aspartic formamide; the aspartic formamide, ethyl acetoacetate and potassium hydroxide are reacted in isopropanol to prepare diene salt (D-2-amino-3N-methylamino oxo-propionic acid diene formamide); the diene salt and pivaloyl chloride are reacted in acetone under the catalysis of pyridine to obtain active anhydride; then the active anhydride is condensed and further protected by deacidification to obtain a target product-crude product of Aspoxicillin. The preparation method for Aspoxicillin has the advantages of cheap and easily-obtained reagent, lower toxicity and lower environment pressure, stable and simple technological operation and high yield.

Description

technical field [0001] The invention relates to the technical field of chemical pharmacy, especially the preparation of primary apoxicillin. Background technique [0002] Apoxicillin is a synthetic penicillin that inhibits the synthesis of bacterial cell walls. Using different parts of Escherichia coli K-12 membrane, the results of affinity for penicillin-binding protein show that this product has high affinity for PBPS-2, 1A, 1BS, and 3 sites, and has strong inhibition on the formation of peptidoglycan bridging effect. This product has strong antibacterial effect on Staphylococcus, Streptococcus, Enterococcus, and Pneumococcus of Gram-positive bacteria, excellent antibacterial effect on Escherichia coli and influenza bacilli of Gram-negative bacteria, and has excellent antibacterial effect on anaerobic bacteria Bacteroides have antimicrobial properties. Combined use with aminoglycoside system antibiotics can achieve synergistic effect. Especially when combined with gent...

AI Technical Summary

Problems solved by technology

In the synthesis process, thionyl chloride is used to react to generate 2-aminomethylamine carbonyloxypropionic acid. This step generates a large amount of black solid with many by-products, and it is reacted with hydrogenation deprotection group, which is very unsafe for industrial production.

[0013] Tang Guang'an from China Pharmaceutical University reported in the literature that apoxicillin was synthesized by the acid anhydride method. This method first uses 2-nitrothiophenol to protect the amino group of aspartic acid, and then further reacts it with pivaloyl chloride. Generate active acid anhydride, then condense with amoxicillin triethylamine salt, and finally deprotect to obtain the target product, such as image 3 , the 2-nitrothiophenol used in the method needs to be prepared separately, which increases the preparation cycle, and is very toxic, and the final deprotection is also inconvenient, and the yield is not high

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