Pneumocandin B0 purification method

Abstract

The present invention provides a pneumocandin B0 purification method, which comprises: extracting a pneumocandin B0 crude product from fermentation broth bacteria residue, carrying out membrane filtration treatment on the crude product, adding an adsorbent to the filtrate to form a solid with adsorbed pneumocandin B0, carrying out CO2 supercritical fluid extraction on the solid, adding a solvent to the obtained extraction solution, crystallizing, carrying out column chromatography separation on the obtained crystal by using an HILIC mode reverse phase silica gel bonded filler as a stationary phase and using an ethanol aqueous solution as a mobile phase, and collecting the pneumocandin B0-containing effluent to obtain the pure product pneumocandin B0. According to the present invention, with the pneumocandin B0 purification method, the separation of PB0 and PC0 can be well achieved, the pneumocandin B0 can be stably and efficiently obtained, the HPLC purity of the pneumocandin B0 can achieve more than 99.4%, and the HPLC purity of the isomer PC0 is as low as 0.01-0.04%; and compared to the existing purification method, the purification method of the present invention has advantagesof simple process operation and good product quality.

Description

technical field [0001] The invention relates to the field of chemistry, in particular to a method for purifying pneumocidine BO. Background technique [0002] Pneumocandin B0 (Pneumocandin B0, referred to as PB0) is a secondary metabolite produced by fungi and is an intermediate in the synthesis of the antifungal drug Caspofungin. Caspofungin is the first echinocandin B drug approved by the US Food and Drug Administration for clinical use. It is a non-competitive inhibitor of β-(1,3)-glucan synthase. It can affect the synthesis of fungal cell walls, thus having antifungal activity. [0003] Neomocontin B0 is produced by fungal fermentation. During the fermentation process, it will produce a variety of products similar in structure to PB0, such as Neomocontin A0 (referred to as PA0), and there is also the isomer of PB0, Neomocontin C0 (abbreviated as PC0). The method for isolating PB0 in is very complicated. [0004] Application No. 201110328804.0 Chinese patent "Preparati...

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Problems solved by technology

And the heat stability of PB0 is relatively poor, should be concentrated under the condition of no more than 50 ℃, yet under this temperature, the concentration of low-concentration water-containing organic solvents, such as the aqueous solution of methanol and ethanol takes a long time, and long-term concentration will cause product quality, The reduction of the yield; and the precipitate after concentration is floc, the centrifugal separation is more difficult, and the production operation is cumbersome

In addition, the medium for normal phase silica gel separation contains water. After repeated use, the increase in the adsorption of water molecules in the normal phase silica gel filler will lead to a decrease in the separation efficiency of the filler, and the separation quality is unstable and fluctuates greatly. The operator needs to replace the filler frequently. The filler must be dried and dehydrated before it can be used again, and the production operation is very troublesome

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