The preparation method of caspofungin

Abstract

The invention relates to a preparation method of caspofungin. The preparation method comprises the following steps: using p-thiocresol to replace hydroxide radicals of pneumocandins B0, then reducing acylamino groups by using a reducing agent, and finally using ethidene diamine to replace p-sulfonyl toluene, thus obtaining the caspofungin. According to the preparation method disclosed by the invention, an appropriate solvent is adopted for crystallizing and separating an intermediate, repeated separation and purification operation for chromatographic column preparation in the prior art is avoided, the reaction time is shortened, degradation of the intermediate is avoided, the operation is simplified, high-purity and high-yield caspofungin is obtained, and the preparation method is particularly suitable for industrial production.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a preparation method of caspofungin. Background technique [0002] Caspofungin is pneumocysin B 0 The semi-synthetic derivative of , the structure is shown below, and its acetate was first listed in the United States in 2001. Caspofungin is a broad-spectrum antibiotic, suitable for empirical treatment of neutropenia, suspected fungal infection in patients with fever, candidemia (syndrome), and candida infection including abdominal abscess, peritonitis, and pleural cavity, Esophageal candidiasis, invasive aspergillosis that is ineffective or intolerable to other treatments, etc. [0003] [0004] Caspofungin is usually composed of pneumocontin B 0 (Pneumocandin B 0 , Formula (I)) is obtained by reducing its amido group with a reducing agent and replacing its hydroxyl group with ethylenediamine. [0005] [0006] William R.Leonard, Jr et al. (J.Org.Chem.2007,72,2335-23...

AI Technical Summary

Problems solved by technology

The 2-mercaptobenzothiazole or 1-phenyl-5-mercapto-tetrazolium used in this method is expensive and difficult to remove after the reaction

[0010] Simultaneously, the second-step reaction product (formula (IV)) in the above-mentioned synthetic method all needs to use preparative chromatographic purification, because chromatographic purification is expensive, complicated to operate, and takes a long time, and the compound of formula (IV) is not stable , is prone to degradation during the purification process, and the degradation products are difficult to separate and purify, so this method is not suitable for industrial production

[0011] Due to the complex chemical structure of caspofungin, many impurities are close to the structure of caspofungin, resulting in similar physical and chemical properties and difficult to separate and purify. pofungin

CN102153616A discloses a method for separating and purifying caspofungin by using a macroporous adsorption resin to obtain caspofungin with a purity >99%. However, the applicant repeated the method disclosed in the application and did not obtain the method disclosed in the specification. technical effect

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