Synthetic method of paclitaxel side chain

Abstract

The invention discloses a synthetic method of a paclitaxel side chain. The method comprises the steps of taking (2R, 3S)-3-phenyl isoserine hydrochloride as a raw material; carrying out esterificationreaction under the participation of methanol and thionyl chloride to obtain (2R, 3S)-phenyl isoserine methyl ester; then preparing (2R, 3S)-N-benzoyl-phenyl isoserine methyl ester through a benzoylation reaction; preparing (4S, 5R)-5-methoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-3-benzoyl-1,3-oxazolidine through a cyclization protection reaction; finally, obtaining a paclitaxel side chain crude product through hydrolysis, and further purifying the paclitaxel side chain crude product through recrystallization to obtain a paclitaxel side chain finished product. The method is simple and easy to operate, short in production period, low in cost, high in purification efficiency and suitable for industrial application and market popularization.

Description

technical field [0001] The invention belongs to the field of chemical synthesis, in particular to a method for synthesizing paclitaxel side chains. Background technique [0002] Since paclitaxel was approved by the US Food and Drug Administration (FDA) in 1992, it has been favored by the international anti-tumor drug research field due to its unique mechanism of action, exact curative effect and less side effects. The number one drug in malignancies such as breast cancer, non-small cell lung cancer and Kaposi'S sarcoma. In the past, the main source of paclitaxel was the bark of the natural yew, but the content was very small, the extraction cost was high, and the natural resources were severely damaged. In recent years, with the rise of yew planting, extracting paclitaxel from yew branches and leaves has become a mainstream method to obtain natural paclitaxel, which not only protects natural plant resources, but also expands the production of natural paclitaxel. However, n...

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Problems solved by technology

[0004] In the existing paclitaxel side chain synthesis patents, there are many ways to prepare by splitting, but the disadvantages are low extraction efficiency, low yield, harsh production conditions, and high investment in cost, resulting in excessive product prices. High, not conducive to the reduction of disease treatment expenditure

There are also some synthetic methods that are prepared by ring-opening epoxy compounds with ammonia and azide compounds, but the ring-opening regioselectivity of these compounds is low, and a large amount of impurities and isomers are produced, which makes the subsequent purification difficult. The low yield of the product is caused, and at the same time, due to the dangerous nature of the azide compound, there is a huge safety hazard in the production operation, and it is not suitable for large-scale production