Method for preparing 10-deacetylbaccatin III by utilizing paclitaxel-semisynthesis impurity

Abstract

The invention relates to a method for preparing 10-deacetylbaccatin III by utilizing a paclitaxel-semisynthesis impurity. A paclitaxel-semisynthesis impurity raw material is dissolved by using an organic solvent; hydrazine hydrate is added into an obtained first mixture to hydrolyze the first mixture; an acidifying agent is added into hydrolyzed mixed liquor to carry out acidification; acidified liquor is neutralized by using weak base, so that the 10-DAB III (10-deacetylbaccatin III) is obtained. According to the method provided by the invention, the paclitaxel-semisynthesis impurity is used as a raw material, is first hydrolyzed by using the hydrazine hydrate, and then is treated by using the acidifying agent to obtain a 10-DAB III coarse product; the 10-DAB III coarse product is purified by using a silica gel chromatographic column to obtain a 10-DAB III product; the 10-DAB III has a yield which is up to 25.6 to 36.8 percent and a content which is up to 98.2 to 99.1 percent; a new approach of obtaining the 10-DAB III product is exploited; not only is the accumulation problem of the impurity in a paclitaxel semisynthesis process solved, but also the raw material is provided for the semisynthesis of paclitaxel; production equipment used in the method provided by the invention is conventional equipment; the used solvent is a conventional solvent; a production condition is easy to implement; the method is simple to operate and suitable for industrialized production. The product can be used for a synthetic raw material for the paclitaxel and docetaxel and is applied to the field of medicines.

Description

technical field [0001] The invention belongs to the field of pharmaceutical chemical synthesis, and specifically relates to a method for preparing 10-deacetylbaccatin III by using semi-synthesized paclitaxel impurities. Background technique [0002] Paclitaxel (trade name: Taxol) is a taxane diterpenoid isolated from the genus Taxus. The total chemical synthesis of paclitaxel has been successful, but the synthetic route is complicated and the cost is too high, which is only of research significance and has no commercial value. Compared with the total synthesis of paclitaxel, the semi-synthesis of paclitaxel is a preparation method with practical value. The semi-synthesis of paclitaxel is generally based on 10-deacetylbaccatin III (10-DAB III), which is similar in structure to the macrocycle of paclitaxel, as a raw material, and paclitaxel, 10-DAB III, is prepared by docking with the side chain of paclitaxel It is usually extracted from Taxus chinensis. Since the content of ...

AI Technical Summary

Problems solved by technology

[0003] The semi-synthesis of paclitaxel through 10-DABⅢ will go through four reaction steps, and each reaction step will produce impurities, and most of these impurities have a 10-DABⅢ structure, such as "Studies on Impurities in Semi-Synthetic Paclitaxel Process" (Wang Yongyi et al., Modern Applied Pharmacy of China February 2014, Volume 31, No. 2), especially the various impurities recorded in Figure 2 on page 155 of the above-mentioned literature, if all these impurities are discarded as waste, it will have a relatively large impact on the output. Small natural 10-DABⅢ causes great waste, so converting impurities containing 10-DABⅢ structure into 10-DABⅢ is another new way to obtain 10-DABⅢ, and there is no conversion of semi-synthetic paclitaxel impurities into 10-de The report of acetyl baccatin Ⅲ, research on this new pathway has obtained a new technical method