Synthesis method of 3,2',6'-tri-N-acetyl gentamicin Cla

A technology based on gentamycin and a synthetic method, which is applied in the field of synthesis of 3,2',6'-tri-N-acetyl gentamycin C1a, can solve the problem that the yield is less than 75%, and achieve The effect of increasing the yield

Active Publication Date: 2010-12-29
CHANGZHOU FANGYUAN PHARMA +1
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Problems solved by technology

The disadvantage of this method i

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Embodiment 1）

[0018] The synthetic method of the present embodiment has the following steps:

[0019] ①Add 1000mL of methanol solvent and 90g of gentamicin C 1a (0.2mol) and 110g of zinc acetate, stirred to fully dissolve, gentamicin C 1a Coordination reaction with zinc acetate to obtain gentamicin C 1a -Zn complexes.

[0020] ②Reduce the temperature of the system in step ① to 0°C to 10°C, add dropwise a mixture of 85mL acetic anhydride (0.9mol), 350mL triethylamine and 150mL tetrahydrofuran to the system in step ① under stirring, and generate 3,2',6'-tri-N-acetylgentamycin C 1a For the acylation reaction of the Zn complex, continue stirring and insulated reaction for 1 h after the dropwise completion. Then add 300mL of purified water to the reacted material, then place it in a rotary evaporator and distill it under vacuum and reduced pressure at a temperature of 60°C until the remaining 300mL of 3,2',6'-tri-N-acetyl Gentamicin C 1a -Concentrated solution of Zn complex, then cooled to...

Embodiment 2～ Embodiment 5）

[0024] The synthetic method of each embodiment is substantially the same as embodiment 1, and difference is: the acetic anhydride used in step 2. and gentamicin C 1a The molar ratio of different, the influence of acetic anhydride dosage on the reaction yield is shown in Table 1.

[0025] Table 1

[0026]

Acetic anhydride and gentamicin C 1a molar ratio

yield

Example 1

4.5∶1

93.9%

Example 2

5∶1

93.6%

Example 3

4∶1

90.2%

Example 4

3.5∶1

87.9%

Example 5

3∶1

85.4%

[0027] As can be seen from Table 1, increasing the amount of acetic anhydride increases the reaction yield, and when the molar ratio reaches 4.5:1, increasing the amount of acetic anhydride decreases the yield instead. Therefore, acetic anhydride and Qingda Mycin C 1a The optimum molar ratio is 4.5:1.

[0028]

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Abstract

The invention discloses a synthesis method of 3,2',6'-tri-N-acetyl gentamicin Cla, comprising the following steps of: carrying out coordination reaction on gentamicin Cla and zinc acetate in a methanol solent at 15-25 DEG C to form a gentamicin Cla-Zn coordination compound; cooling to 0-10 DEG C, dropwise adding and stirring a mixed solution prepared from acetic anhydride, triethylamine and tetrahydrofuran to the gentamicin Cla-Zn coordination compound, continuing stirring to make the mixture react for 1-2h after finishing dropwise adding the mixed solution, adding water, and carrying out reduced pressure distillation to obtain a concentrated solution containing a 3,2',6'-tri-N-acetyl gentamicin Cla-Zn coordination compound; and introducing the concentrated solution into a chromatographic separation column for sampling, washing with purified water, resolving with an ethanol water, collecting effective constituents at the outlet of the chromatographic separation column, carrying out reduced pressure concentration to a collected solution, and finally freezing and drying to obtain a finished product of the 3,2',6'-tri-N-acetyl gentamicin Cla. The method of the invention has higher yield.

Description

technical field [0001] The invention relates to a synthesis method of a medical raw material intermediate, in particular to a 3,2',6'-tri-N-acetyl gentamicin C 1a synthetic method. 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 reduced pr...

Claims

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Application Information

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IPC IPC(8): C07H15/236C07H1/00
Inventor 封成军李兴刚胡东辉毕晓明苏晓春狄绍炎
Owner CHANGZHOU FANGYUAN PHARMA
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