Preparation method of etimicin sulfate

Abstract

The invention relates to a preparation method of etimicin sulfate. The preparation method includes following steps: taking gentamicin C1a base, dissolving in a solvent of a certain proportion, addinga complexing agent of a certain proportion, adding an amino protection agent of a certain proportion, maintaining for certain time, adding a solvent and ammonia water of a certain proportion, stirring, skimming, and concentrating to obtain a first intermediate; taking a reducing agent of a certain proportion, adding a solvent and acetic acid of a certain proportion, maintaining for certain time, adding the first intermediate, allowing reaction for a period of time, adding a strong alkaline solution to adjust pH, filtering, and concentrating to obtain a second intermediate; adding a solvent anda palladium carbon catalyst of a certain proportion, allowing reaction at certain hydrogen pressure and temperature, filtering, concentrating, using resin for adsorption, using ammonia water for resolving, concentrating, using sulfuric acid to adjust pH, removing carbon, filtering, and drying to obtain etimicin sulfate.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a preparation method of etimicin sulfate. Background technique [0002] The Chinese patent whose authorization notification number is CN1040177 discloses a kind of 1-N-ethyl gentamicin C 1a The medicinal preparation and preparation method of its salt: first, with gentamicin C 1a As the starting material, form a complex with cobalt acetate in water and aprotic solvents (dimethylformamide, dimethyl sulfoxide, etc.), and acetylate with acetic anhydride to obtain 3,2',6'- Tris-N-acetylgentamycin C 1a (referred to as P1) reaction solution, and then through 732 (H + ) resin and YPR-II resin to obtain intermediate P1. Next, the intermediate P1 is directly reacted with acetaldehyde under acidic conditions and reduced by sodium borohydride to obtain 3,2’,6’-tri-N-acetyl-1-ethylgentamycin C 1a (referred to as P2) aqueous solution, the aqueous solution is purified by YPR-II resin, and then hydr...

AI Technical Summary

Problems solved by technology

[0005] Although the method has greatly improved the yield, it is more cumbersome to operate

First, the application of nanofiltration technology requires real-time detection of the content of Zn ions in the solution, which requires high equipment and instruments; second, the intermediate P1 is extremely sensitive to water vapor after silicon etherification, and the cool water vapor in the system can easily lead to silicon ether The failure of the reaction will affect the reaction effect, and the operation requirements are harsh; third, it is easy to make 1-NH 2 Corresponding silicon etherification also occurs, which hinders the reaction of 1-N with acetaldehyde, and finally forms the by-product gentamicin C 1a ; Fourth, the reaction material acetaldehyde has a boiling point of 20.8°C, which is highly toxic and easily vaporized and polymerized, making it difficult to store and inconvenient to use

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