Synthesis method of amikacin

Abstract

The invention discloses a synthesis method of amikacin. The synthesis method comprises following steps: firstly, a partially silanization protection product of kanamycin A is prepared; dehydration of the partially silanization protection product with PHBA under the action of DCC is carried out so as to obtain a acylated product; the acylated product is subjected to hydrolysis, nitrilase, and column chromatography purification so as to obtain amikacin. According to the synthesis method, NOP is not used, synthesis of an active ester via esterification is avoided, damage on the health of workers is reduced greatly, solid waste generated in production process is reduced greatly, product yield is increased, and the synthesis method is especially suitable for industrialized production.

Description

technical field [0001] The invention relates to a synthesis method of amikacin, which belongs to the field of medicine. Background technique [0002] Amikacin acid is a semi-synthetic aminoglycoside antibiotic with a broad antibacterial spectrum and strong antibacterial ability against a variety of bacteria. Since its launch in the 1970s, amikacin sulfate has been widely used due to its definite curative effect, and has become the first-line anti-infective drug commonly used clinically in the world. In my country, Amikacin Sulfate has been included in the National Essential Drug List, and also included in the Class A drug in the "National Basic Medical Insurance and Work Injury Insurance Drug List". [0003] Amikacin, also known as amikacin. The most commonly used in the existing amikacin synthesis route is the silylation protection route, which comprises: (1) taking kanamycin A as raw material to obtain the silylation protection product of kanamycin A through silylation p...

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Problems solved by technology

[0006] The above route has the following problems: (1) 7 hydroxyl groups and 4 amino groups of Kanamycin A need to be fully silanized for protection, requiring a longer reaction time; (2) in order to improve the activity of the PHBA carboxyl group, use NOP and PHBA to form The active ester is acylated, and the active ester is removed from the NOP after the acylation reaction

This not only causes the complexity of the process, but also because NOP is a highly sensitizing substance, it will cause damage to the health of workers when used as a raw material and as a by-product in the aftertreatment process (such as separating out NOP in the recovery of acetone); (3) in actual production, Most of the NOP as a by-product enters the hydrazinolysis step with the material, and NOP forms phthalic hydrazide under the action of hydrazine. Due to the poor purity of phthalic hydrazide, the reuse value is low. In addition, the by-product It is not easy to biodegrade and has great harm to the environment. The general treatment method is incineration, but it still causes certain harm to the environment.

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