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## PREPARATION METHOD OF MICAFUNGIN SODIUM 

## CROSS-REFERENCE TO RELATED APPLICATIONS 

This application is a 371 National Phase of PCT/CN2012/ 075339, filed on May 11, 2012, which claims benefit of and priority to CN 201110121705.5, filed on May 12, 2011, which is incorporated herein by reference in its entirety for all purposes. 

The invention involves purification of compounds, particu- larly a preparation method for Micafungin sodium. 

Micafungin is a second clinically applied pneumocandins drug after caspofungin. It mostly inhibits the synthesis of the main ingredient of fungi cell walls, i.e. 1,3-~-D-dextran, and therefore disrupts the formation of fungi cell walls and influ› ences cell morphology and osmotic pressure thereof, thus leading to cytolysis and cell death. Micafungin is mainly used for treating deep fungi infections such as that from Monilia, Aspergillus, etc. In particular, it is used for treating fungi infections in patients with low immunity, such as chemo› therapy patients, AIDS patients, etc. Clinically, it is also used in combination with amphotericin and triazole anti-fungi drugs. 

Micafungin is developed by Fujisawa Pharmaceutical, under the trade name of Mycamine. Micafungin is on the market as sodium form, the formula of which is shown as follows. 

<img src='content_image/940428.jpg'>

WO9611210 and WO2004014879 have reported processes for synthesis and purification of micafungin. 

WO9611210 has reported a method for obtaining the sodium salt by using cation exchange resin (DOWEX- 50WX4). It is impossible to control the pH value of the product using said method. In addition, this method only applies to small-scale preparation. It is hardly suited for expanded scale of production and quality of products thereof is unmanageable. 

WO2004014879 has reported a method using 0.1 mol/L NaOH solution to adjust pH value to 6-8. The Inventors have performed multiple experiments using methods reported in the literature and have discovered that adjusting the pH value 

## FIELD OF INVENTION 

## BACKGROUND 

according to said method leads to a significant rise in the content ofimpurity from micafungin degradation, as is shown in FIGS. 2 and 3, thereby considerably increasing the diffi› culty in the subsequent separation and purification and it is difficult to prepare micafungin sodium of high purity. Hence, the method can not fulfil the requirements for industrialized manufacture. 

Therefore, it is urgent to develop a method for the prepa› ration of micafungin sodium in order to obtain micafungin sodium of high purity. 

The Invention aims at providing a convenient method for the preparation of micafungin sodium. 

Another objective of the Invention is to provide a prepara› tion method of micafungin sodium which is adapted for the industrial production. 

In the first aspect of the Invention, a preparation method for the compound of formula II is provided, comprising steps as follows: 

mixing a weak base solution with a water solution contain› ing the compound of formula I or a mixture solution of water and organic solvent( s) containing the compound of formula I, and thereby obtaining the compound of formula II; 

<img src='content_image/940429.jpg'>

<img src='content_image/940430.jpg'>

## SUMMARY OF INVENTION 

