Method for semisynthesis of Docetaxel and intermediate of Docetaxel

Abstract

The invention relates to a method for semisynthesis of Docetaxel and an intermediate of the Docetaxel. The method provided by the invention comprises the steps of firstly, carrying out hydroxyl protection on C7 and C10 of 10-DAB III (10-deacetylbaccatin III) by using 2,2,2-trichloroethylchloroformate so as to obtain an intermediate I, subjecting the intermediate I to a reaction with a side chain radical compound so as to prepare an intermediate II, subjecting the intermediate II to a hydrogenation reaction under the catalysis of palladium-charcoal so as to prepare an intermediate III, subjecting the intermediate III to a reaction under acidic conditions so as to obtain a Docetaxel crude product, and subjecting the Docetaxel crude product to purification, thereby obtaining a purified product. According to the method provided by the invention, the 10-DAB III raw material can be sufficiently utilized, finally-produced byproducts are few, the final product Docetaxel has the purity of 99.6% to 99.9%, the mole yield reaches up to 73% to 82%, and the utilization ratio of the 10-DAB III can be greatly increased.

Description

technical field [0001] The invention belongs to the field of pharmaceutical chemical synthesis, and in particular relates to a method for semi-synthesizing docetaxel and an intermediate thereof. Background technique [0002] Docetaxel (trade name Taxotere) is a taxane diterpenoid compound that is chemically synthesized or semi-synthesized. [0003] The mechanism of action of docetaxel is to enhance tubulin polymerization and inhibit microtubule depolymerization, leading to the formation of stable non-functional microtubule bundles, thereby disrupting the mitosis of tumor cells. The intracellular concentration of docetaxel is 3 times higher than that of paclitaxel, and the intracellular residence time is longer, which is an important reason why docetaxel has greater antitumor activity than paclitaxel in vitro. In the in vivo test, it is effective against colon cancer, breast cancer, lung cancer, and ovarian tumor transplantation in mice. [0004] However, in the prior art, ...

AI Technical Summary

Problems solved by technology

[0005] The common problem in the semi-synthetic method of docetaxel in the prior art is: using 10-DABⅢ as a raw material, the final yield of docetaxel is low

The main reasons for this problem are as follows: (1) in the process of carrying out hydroxyl protection to 10-DABⅢ 7-position hydroxyl and 10-position hydroxyl, it is easy to form simultaneous protection of 7-position hydroxyl, 10-position hydroxyl and 13-position hydroxyl, resulting in expensive 10-position - DABⅢ raw material waste; (2) During the reaction process of deprotection, the main intermediate raw material is easy to react to generate other impurities; (3) During the purification and separation process of docetaxel, column chromatography and recrystallization are used for purification , thus resulting in the loss of some docetaxel products

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