Synthesis method of cytochalasin compound flavipesine A

A technology of cytochalasin and synthesis method, which is applied in the field of synthesis of cytochalasin compound flavipesineA, which can solve the problems of high cost, long cycle and high price, and achieve the effects of low cost, short production cycle and high production efficiency

Active Publication Date: 2021-07-20
NANKAI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the currently reported synthesis methods of cytochalasin generally have disadvantages such as many steps, low yield, high toxicity of reagents, and high price, which are not enough to meet the needs of its modification and improvement.
[0005] At present, no feasible chemical synthesis method for cytochalasin-like skeleton compounds has been reported, and the existing bio-fermentation extraction methods have disadvantages such as high cost, low yield, long cycle, difficult separation of products, and low purity.
The separation method reported in the literature can basically only obtain milligram-level products from dozens or even hundreds of grams of crude extract, and the efficiency of biological fermentation methods is low.

Method used

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  • Synthesis method of cytochalasin compound flavipesine A
  • Synthesis method of cytochalasin compound flavipesine A
  • Synthesis method of cytochalasin compound flavipesine A

Examples

Experimental program
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Effect test

Embodiment 1

[0032] Embodiment 1 of the present invention provides the synthetic method of compound B used in the present invention, specifically as follows:

[0033]

[0034] Mix p-toluenesulfonic acid (2.27mmol) and 2,2,6,6-tetramethylpiperidine oxide (2.34mmol) in 15mL dichloromethane solution under ice bath, and continue stirring (400rpm) for 10min under ice bath Finally, the dichloromethane solution of this mixture was added to the 7 mL dichloromethane solution of compound D (0.38 mmol), and the stirring (400 rpm) was continued for 1 h under ice bath, and then the reaction was quenched with 10 mL saturated aqueous sodium bicarbonate solution under ice bath (10min), extracted with ethyl acetate at room temperature, washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered under reduced pressure (500mbar), and concentrated under reduced pressure (150mbar), the crude product obtained was purified by silica gel column Analysis and purification (V ethy...

Embodiment 2

[0040] A kind of synthetic method of cytochalasin compound flavipesine A, its synthetic route is specifically as follows:

[0041]

[0042] Specific steps are as follows:

[0043] (1) Dissolve compound B (0.075mmol) in 1.5mL of anhydrous tetrahydrofuran at room temperature, add zinc powder (0.90mmol) and ammonium acetate (1.05mmol), then stir (450rpm) at 40°C for 2h, and then At room temperature, filter through diatomaceous earth (500mbar) and concentrate under reduced pressure (150mbar) to obtain the crude product, which is purified by silica gel column chromatography (eluent: V ethyl acetate: V petroleum ether = 50:50) to obtain intermediate C (26.9mg, yield rate is 89%);

[0044] (2) Dissolve Intermediate C (0.05mmol) in 1mL of anhydrous tetrahydrofuran at room temperature, add scandium trifluoromethanesulfonate (0.25mmol), stir (450rpm) for 2h, and then add 1mL of saturated sodium bicarbonate at room temperature The reaction was quenched with aqueous solution (10min),...

Embodiment 3

[0046]

[0047] (1) Dissolve compound B (0.075mmol) in 0.15mL anhydrous tetrahydrofuran at room temperature, add zinc powder (0.75mmol) and ammonium acetate (0.90mmol), then stir (450rpm) at 40°C for 2h, and then Filtration through diatomaceous earth (500mbar) at room temperature and concentration under reduced pressure (150mbar) gave the crude product, which was purified by silica gel column chromatography (V ethyl acetate: V petroleum ether = 50:50) to obtain intermediate C (22mg, yield 73%);

[0048] (2) Dissolve Intermediate C (0.05mmol) in 0.1mL of anhydrous tetrahydrofuran at room temperature, add scandium trifluoromethanesulfonate (0.20mmol), stir (450rpm) for 2h, and then add 1mL of saturated bicarbonate The reaction was quenched with sodium aqueous solution (10min), extracted with ethyl acetate, washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered under reduced pressure (500mbar), and concentrated under reduced press...

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Abstract

The invention discloses a synthesis method of a cytochalasin compound flavipesine A. The synthesis method comprises the following steps: 1) dissolving a compound B in tetrahydrofuran, adding a reducing agent at room temperature, and reacting at 40 DEG C to obtain an intermediate C; and 2) adding a reaction reagent into the tetrahydrofuran solution of the intermediate C at room temperature to obtain a compound A. Reagents used in the synthesis process provided by the invention can be commercially purchased at low price, and the reaction strategy is also suitable for synthesis of other types of similar intermediate product derivatives of cytochalasin, so that a foundation is laid for structural modification, structure-function relationship research, new drug development and large-scale preparation of the alkaloid.

Description

technical field [0001] The invention relates to the technical field of chemical synthesis, in particular to a synthesis method of flavipesine A, a cytochalasin compound. Background technique [0002] Natural products with complex and diverse structures have always been an important source for the discovery of small molecule drugs. Although natural products have rich and diverse structures, their natural sources are often very limited, and it is difficult to conduct in-depth studies on their chemical properties and biological activities. Therefore, how to be concise and efficient , Obtaining a large number of natural products and their analogs with specific structures has become an important research content of natural product chemical synthesis, biosynthesis and organic synthesis methodology. [0003] Cytochalasins are a class of fungal polyamino acid hybrid secondary metabolites with significant biological functions. So far, more than 400 different compounds in this family...

Claims

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Application Information

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IPC IPC(8): C07D491/107
CPCC07D491/107Y02P20/55
Inventor 邓军吴海丁一鸣龙先文曲春雷
Owner NANKAI UNIV
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