Separation purification method and use of echinocandin B

Abstract

The invention provides a method for separating echinocandin B from fermentation broth and a use of echinocandin B. The method comprises the following steps that through fermentation broth acidification, extraction and concentration, concentrated liquid is obtained; and the concentrated liquid is fed into a reverse phase silica gel column and then is subjected to separation and concentration so that echinocandin B is obtained. The echinocandin B separated by the method has high purity and is a good raw material for preparation of echinocandin cyclopeptide parent nucleus and antifungal drugs. The method has a high finished product yield, utilizes safe and cheap solvent and instruments, has a low production cost and simple processes and is suitable for industrial production.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to a method for separating echinocandin B from fermentation broth and its application. Background technique [0002] Echinocandins are a group of natural products discovered in the late 1970s. They have similar structural features of cyclic polypeptide cores and different fatty acid side chains, and can non-competitively inhibit fungal cell walls. β -1,3-glucan synthase activity, clinically used as an antifungal drug. [0003] Echinocandin B (ECB for short) is produced by Aspergillus nidulans ( Aspergilus nidulans ) metabolism, is one of echinocandins, and its structure is as follows: [0004] [0005] Echinocandin B is subjected to deacylase to obtain the cyclic peptide core, and the cyclic peptide core can be chemically modified to prepare the antifungal drug Anidulafungin. In order to improve the efficiency of deacylation of ECB and the quality of ECB nuclei, ...

AI Technical Summary

Problems solved by technology

[0006] Most of the separation techniques for echinocandin B in the prior art are separated by macroporous resin and silica gel chromatography, as US Patent No. 4,968,608 discloses a method of using Macroporous resin HP20, dextran gel LH20 and normal phase silica gel to separate and purify the method to obtain ECB from the fermentation broth. The adaptability of the extraction liquid is poor; U.S. Patent US6506726 improves this, and uses macroporous resins such as HP20, SP825, SP207 and CG-161 to separate and purify ECB after acidifying the fermented liquid. This method is relatively simple but the separation effect is not good, and the product purity is lower than 80%, there is also the disadvantage of poor adaptability to the fermented mycelia extract containing more than 2% methyl oleate

At the same time, U.S. Patent No. 4,288,549 also discloses a method for purifying echinocandin B by using silica gel column, extraction and other methods, but this method needs to be carried out under relatively high pressure conditions, which makes it difficult to scale up the preparation process and has a negative impact on upstream fermentation. The pigment in the liquid cannot be removed well

Excessively high impurity components in echinocandin B will inevitably lead to a decrease in the quality of the cyclic peptide core obtained by deacylase, thereby affecting the quality of antibacterial drugs that use it as an active ingredient

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