Method for semi-synthesis of paclitaxel on industrialized basis

Abstract

The invention provides a method for the semi-synthesis of paclitaxel on an industrialized basis. The method comprises the following steps: a) acetylating the 10-hydroxyl in the presence of CeCl3.6H2O as a high-efficiency specific catalyst to obtain baccatin III through the reaction; b) protecting the C-7-hydroxyl in the presence of trichloroethyl chloroformate to obtain baccatin III, wherein the C-7 position of baccatin III is protected; c) conducting the esterification reaction between the baccatin III obtained in the reaction of step b) and (4S, 5R)-3-benzoyl-2-(4-methoxyphenyl)-4-phenyl-5-oxazolinyl carboxylate to obtain the following derivatives; and d), opening the oxazole ring on the ring-shaped lateral chain of (4S, 5R)-3-benzoyl-2-(4-methoxyphenyl)-4-phenyl-5-oxazolinyl baccatin III, and synchronously removing the 7-protective group to obtain paclitaxel. The method of the invention breaks with the conventional method which sequentially comprising the steps of protecting the 7-position hydroxyl and acetylating the 10-position hydroxyl, so that the method has the advantages of shorter reaction time and less by-products; the yield of single-step reaction reaches 90%; and eachstep of reaction is conducted at normal pressure in the absence of protective inert gases. Therefore, the method is suitable for industrialized production.

Description

technical field

[0001] The invention relates to an industrial production method for preparing paclitaxel from 10-deacetylbaccatin III as a raw material. Background technique

[0002] Paclitaxel is a diterpenoid compound extracted from the yew plant, which has a unique anti-cancer mechanism of inhibiting mitosis, and is internationally recognized as the drug with the best anti-cancer effect. According to the report of the World Health Organization, the incidence of cancer in the world has shown an obvious increasing trend in recent decades. From 1991 to 2000, the incidence and death of cancer worldwide increased by 22%. In 2000, the number of new cancers in the world exceeded 10 million, and the number of deaths caused by cancer was about 6.3 million people in the world every year, accounting for the total number of deaths. nearly 12 percent. The World Health Organization predicts that by 2020, the annual number of new cancer patients will reach 15 million, and cancer will ...

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