Safer preparation method of echinocandin antifungal medicament

A compound, caspofungin technology, applied in the direction of peptides, etc., can solve the problems of odor and irritation, unsuitable for industrial production, etc., and achieve the effect of safety in the preparation process

Inactive Publication Date: 2011-10-19
SHENZHEN JYMED TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The three-dimensional structure selection accelerator used in this method is thiophenol, which is a

Method used

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  • Safer preparation method of echinocandin antifungal medicament
  • Safer preparation method of echinocandin antifungal medicament
  • Safer preparation method of echinocandin antifungal medicament

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] The reaction process is as follows:

[0028]

[0029] Neomercontin B0(1-1)

[0030]

[0031]

[0032] Process flow:

[0033] Compound (1-1) neomocontin B0 (150.20g, 141.0mmol), trifluoromethanesulfonic acid (37.35mL, 423mmol), phenylboronic acid (34.38g, 282mmol), 2-mercaptobenzothiazole (70.74g, 423mmol ) was added to anhydrous acetonitrile (4.5 L). The suspension was cooled to -15°C and kept, detected by HPLC, until the reaction was complete (2.5h). The reaction product was cooled rapidly, and 450mL NaAc·3H 2 O (57.45 g, 423 mmol) in water precipitated the product. The suspension was warmed to room temperature for 2 h, then cooled to below 0 °C. The product was isolated by filtration, and the product was purified by chromatography, eluting with 1:9 (v / v) H2O / CH3CN to obtain the eluate of compound (1-2), which was concentrated and dried to obtain 163.98 g of compound (1-2), which was measured by HPLC. Its purity is 94% (with reference to the standard), a...

Embodiment 2

[0044] The reaction process is as follows:

[0045]

[0046] Neomercontin B0(2-1)

[0047]

[0048]

[0049] Process flow:

[0050] Compound (2-1) Neomocontin B0120g, 112.8mmol), trifluoromethanesulfonic acid (29.88mL, 338.4mmol), phenylboronic acid (27.48g, 225.6mmol), 1-phenyl-5-mercapto-tetrazolium (60.24 g, 338.4 mmol) was added to anhydrous acetonitrile (3.6 L). The suspension was cooled to -15°C and kept, detected by HPLC, until the reaction was complete (2.5h). The reaction product was rapidly cooled and added to 399.6mL NaAc·3H 2 The product was precipitated from aqueous O (45.96 g, 338.4 mmol). The suspension was warmed to room temperature for 2 h, then cooled to below 0 °C. The product was isolated by filtration and the product was purified by chromatography, 1:9 (v / v) H2O / CH 3 CN was eluted to obtain the eluate of compound (2-2), which was concentrated to obtain 135.25 g of compound (2-2), the purity of which was measured by HPLC was 93% (with the sta...

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PUM

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Abstract

The invention belongs to the technical field of organic synthesis and provides a method for preparing caspofungin. The preparation method of the caspofungin comprises the following steps: a) reacting a compound II with phenylboronic acid and a stereochemical structure selecting agent so as to generate a compound III, wherein the stereochemical structure selecting agent is 2-sulfydryl benzothiazole or 1-phenyl-5-sulfydryl-tetrazole; b) reducing the compound III into amine, namely, a compound IV; and c) finally reacting the compound IV with quadrol for substitution, so as to obtain a target compound. According to the preparation method of the caspofungin, the non-toxic stereochemical structure selecting agent is adopted, so that the preparation process is safer and the preparation method is more suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation method of an antifungal drug, in particular to a preparation method of a safer Echinococcus antifungal drug. Background technique [0002] Caspofungin, whose structural formula is shown in (I), has been widely used in the preparation of antifungal preparations for treatment or prevention. [0003] [0004] William R. Nader (William R.Leonard, Jr.) etc. in the paper (Synthesis of the Antifungal -1,3-Glucan Synthase InhibitorCANCIDAS (Caspofungin Acetate) from Pneumocandin B0) mentions that pneumocandin B0 (pneumocandin B0) is used as the starting material to prepare caspofungin. The stereostructure selection accelerator used in the method is thiophenol, which is a highly toxic chemical with foul smell and irritation, and is not suitable for industrial production. Contents of the invention [0005] The purpose of the present invention is to overcome the deficiencies of the prior art and provide a more stabl...

Claims

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Application Information

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IPC IPC(8): C07K7/56
Inventor 张健存李新宇姚志勇支钦
Owner SHENZHEN JYMED TECH
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