4'-demethylpodoph-yllotoxin derivative, its production and use

Abstract

A 4'-demethylepipodophyllotoxin derivative IIIa-n is prepared by taking etoposide as raw material, reacting with sodium iodide to generate 4-bit iodine substitute and obtain intermediate II, agitating while adding into barium carbonate, regulating reactive system pH 7-8, adding into amino-compound, and reacting to room temperature for 8-10 hrs to obtain final product. It's simple and efficient, it can avoid 4-bit surface isomerization and 4-bit demethylation, it has strong inhibiting function of multiple tumor cell strain and non-toxic.

Description

4'-norepipodophyllotoxin derivative and its preparation method and use technical field The invention belongs to a synthesis method of organic compounds, and relates to a 4'-norepipodophyllotoxin derivative and a preparation method, mainly involving 4β-substituted amino-4-deoxy-4'-norepipodophyllotoxin derivatives and The preparation method, and the application in the preparation of antitumor drugs. Background technique Etoposide is a semi-synthetic derivative of the natural product podophyllotoxin. As a kind of glycoside compound with high anti-tumor activity, it is widely used in the clinical treatment of testicular cancer, lymphoma, leukemia, non-small cell lung cancer, acute myeloid leukemia and other cancers. treat. Etoposide acts as a TopoII inhibitor to exert antitumor effects. Since TopoII is a cell cycle-dependent enzyme and a good substrate for P170 glycoprotein, tumor cells are more likely to develop drug resistance to TopoII than TopoI; in addition, cancer ce...

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Problems solved by technology

Since TopoII is a cell cycle-dependent enzyme and a good substrate for P170 glycoprotein, tumor cells are more likely to develop drug resistance to TopoII than TopoI; in addition, cancer cells are transformed from normal cells, and the two types of cells The difference is not significant. While killing cancer cells, etoposide can damage normal cells in the body, especially bone marrow and intestinal mucosal cells that divide rapidly, resulting in myelosuppression, neutropenia, and nausea. , hyaline membrane disease and changes in normal respiratory function and other toxic and side effects, thereby inhibiting the dosage of the drug and hindering the efficacy of the drug

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