Podophyllinic acid lactone derivant and preparation method thereof

A technology of podophyllotoxin and derivatives, which is applied in the field of preparation of water-soluble podophyllotoxin derivatives, can solve the problems that the preparation method has not been reported, and achieve the benefits of absorption and metabolism, water solubility and fat solubility, and improve dissolution performance effect

Inactive Publication Date: 2008-12-03
NINGBO UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] There are reports on podophyllotoxin derivatives in the Chinese patent literature library, but there

Method used

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  • Podophyllinic acid lactone derivant and preparation method thereof
  • Podophyllinic acid lactone derivant and preparation method thereof
  • Podophyllinic acid lactone derivant and preparation method thereof

Examples

Experimental program
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Example Embodiment

[0022] The preparation route of the present invention is:

[0023] Put podophyllotoxin and carboxyl monomethoxy polyethylene glycol in the reaction vessel, add dicyclohexylcarbodiimide and dimethylaminopyridine, mix the reactants uniformly, and react under microwave catalysis for 30 minutes, that is Podophyllotoxin prodrugs can be prepared.

Example Embodiment

[0024] Example 1

[0025] In a 25 ml Erlenmeyer flask, add 1.00g (0.5mmol) mPEG-COOH 2000, 0.31g (0.75mmol) podophyllotoxin, 0.21g (1.0mmol) dicyclohexylcarbodiimide and 0.12g (1.0mmol) pair -N,N-Dimethylaminopyridine, shake well to mix the reactants evenly, then place it in a Whirlpool microwave oven and heat it at 510W power for 30min until no more water droplets are formed. After the reaction mixture was placed in a vacuum drying oven to dry and cool, 40 ml of anhydrous dichloromethane was added, shaken well, filtered, and after part of the dichloromethane was evaporated from the filtrate, 80 ml of anhydrous ether was added to precipitate a white precipitate. The above sample was placed in a refrigerator at 4-10°C to cool, filtered with suction, and dried to obtain a white solid weighing 1.22g.

[0026] In the above crude product, add 40ml of dichloromethane to dissolve it, then add 20ml of 10% AcOH / THF to decompose the excess dicyclohexylcarbodiimide, wash with 20ml of 0.1N hy...

Example Embodiment

[0027] Example 2

[0028] In a 25 ml Erlenmeyer flask, add 2.50g (0.5mmol) mPEG-COOH 5000, 0.31g (0.75mmol) podophyllotoxin, 0.21g (1.0mmol) dicyclohexylcarbodiimide and 0.12g (1.0mmol) pair -N,N-Dimethylaminopyridine, shake well to mix the reactants evenly, then place it in a Whirlpool microwave oven and heat it at 510W power for 30min until no more water droplets are formed. After the reaction mixture was placed in a vacuum drying oven to dry and cool, 40 ml of anhydrous dichloromethane was added, shaken well, filtered, and after part of the dichloromethane was evaporated from the filtrate, 80 ml of anhydrous ether was added to precipitate a white precipitate. The above sample was placed in a refrigerator at 4-10°C for cooling, suction filtered, and dried to obtain a white solid weighing 2.66 g.

[0029] In the above crude product, add 40ml of dichloromethane to dissolve it, add 20ml of 10% AcOH / THF to decompose the excess dicyclohexylcarbodiimide, wash with 20ml of 0.1N hydroch...

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Abstract

The invention provides a derivative for podophyllotoxin. The derivative is characterized in that the derivative is a carboxyl single methoxypolyethylene glycol derivative of podophyllotoxin with the following structural formula. The preparation method comprises the following the steps that: the podophyllotoxin, the carboxyl single methoxypolyethylene glycol, dicyclohexyl imine and N dimethylaminopyridine are used as raw materials to prepare the polyethylene glycol derivative of the podophyllotoxin by the microwave catalytic action. The podophyllotoxin prodrug of the derivative is good in solubility and high in stability. The preparation of the derivative has the characteristics of high efficiency, rapidness, simpleness and convenience and high reaction yield.

Description

technical field [0001] The invention relates to a method for preparing water-soluble podophyllotoxin derivatives, which are polyethylene glycol modified podophyllotoxin derivatives. Background technique [0002] Podophyllotoxin is a natural compound with anti-tumor activity. It has strong cytotoxicity, but due to its serious toxicity, it cannot be used in clinical practice. Its structure needs to be modified. Pharmacists have synthesized a large number of Podophyllotoxin derivatives, and a structure-activity relationship study was carried out. Such as: etoposide, teniposide and other podophyllotoxin derivatives have been developed into anti-tumor drugs for clinical application. Modification of podophyllotoxin with polymer compounds is another important method to reduce the side effects of podophyllotoxin. Lignin, polyethylene glycol and its derivatives are all used as modifiers of podophyllotoxin. [0003] There are reports on podophyllotoxin derivatives in the Chinese pat...

Claims

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Application Information

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IPC IPC(8): A61K47/48A61K31/365A61P35/00C07D493/04A61K47/60
Inventor 张剑锋侯琳熙
Owner NINGBO UNIV
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