Method for preparing 3,2',6'-tri-N-acetyl gentamicin C1a

Abstract

The invention discloses a method for preparing 3,2',6'-tri-N-acetyl gentamicin C1a, which comprises the following steps of: (1) performing coordination reaction on gentamicin C1a and zinc acetate in a methanol solvent at the temperature of between 15 and 25 DEG C to prepare a gentamicin C1a-Zn complex; (2) reducing the temperature of the system of the step (1) to between 0 and 10 DEG C, dropwise adding mixed liquid consisting of acetic anhydride, triethylamine and tetrahydrofuran with stirring for acylation reaction to prepare 3,2',6'-tri-N-acetyl gentamicin C1a-Zn complex, after dropwise adding, continuously stirring and reacting for 1 to 2 hours, and adding water and distilling under reduce pressure to prepare concentrated solution containing the 3,2',6'-tri-N-acetyl gentamicin C1a-Zn complex; and (3) performing after treatment on the concentrated solution prepared by the step (2) to prepare a 3,2',6'-tri-N-acetyl gentamicin C1a finished product. The method has the advantage of higher yield.

Description

technical field

[0001] The invention relates to a preparation method of a medical raw material intermediate, in particular to a 3,2',6'-tri-N-acetyl gentamicin C 1a method of preparation. Background technique

[0002] Chinese patent document CN1040177C (application number 93112412.3) discloses a 1-N-ethyl gentamicin C 1a Pharmaceutical formulations and preparation methods of salts thereof.

[0003] of which gentamicin C 1a Preparation of 3,2',6'-tris-N-acetylgentamycin C 1a The method is: at room temperature, the gentamicin C 1a Dissolve in water and non-protic polar organic solvents (such as dimethylformamide, dimethyl sulfoxide, etc.), then add cobalt acetate, and then add dropwise the THF solution of acetic anhydride until the reaction is completed. The post-treatment is: dilute the reaction solution with water, and then pass through the strongly acidic 732 (H + ) resin column adsorption, followed by water washing, ammonia water analysis, and concentration under red...