Water-soluble 4í»-nor-epipodophyllotoxin derivant and preparation method thereof

Abstract

The invention provides a derivative of a water soluble 4'-nor epipodophyllotoxin. The derivative is characterized in that the derivative is a polyethylene glycol derivative, the structure formula of which is the 4'- nor epipodophyllotoxin. The preparation method comprises the following the steps that: the 4'- nor epipodophyllotoxin, carboxyl single methoxypolyethylene glycol, dicyclohexyl imine and N dimethylaminopyridine are used as raw materials to prepare the polyethylene glycol derivative of the 4'- nor epipodophyllotoxin by the microwave catalytic action. The 4'- nor epipodophyllotoxin prodrug of the invention is good in solubility and high in stability. The preparation of the invention has the characteristics of high efficiency, rapidness, simpleness and convenience and high reaction yield.

Description

technical field

[0001] The invention relates to a water-soluble derivative of 4'-norepipodophyllotoxin and a related preparation method, which is a derivative of 4'-norepipodophyllotoxin modified by polyethylene glycol. 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 directly used in clinical practice. It must be modified through its structure, such as: etoposide , teniposide and other podophyllotoxin derivatives have been developed into antineoplastic drugs for clinical application. The structure-activity relationship studies of podophyllotoxins show that podophyllotoxins and their analogs must meet the following conditions to maintain their anticancer activity: (1) there is a phenolic hydroxyl group at the 4'-position; (2) the C-4 substituent position is β configuration; (3) has a trans-lactone ring. Therefore, people epimerized 4'-norpodophyllotoxin on...

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