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paclitaxel(33069-62-4)

Overview: Taxol is a monomer diterpenoid compound extracted from the bark of the natural plant Taxus. It is a complex secondary metabolite and is also the only drug known to promote microtubule polymerization and stabilize polymerized microtubules. Isotopic tracing showed that paclitaxel only bound to the polymerized microtubules and did not react with the unpolymerized tubulin dimer. Cells exposed to paclitaxel will accumulate a large number of microtubules in the cells. The accumulation of these microtubules interferes with various functions of the cells, especially stops the cell division at the mitotic stage, and blocks the normal cell division. Through Ⅱ - Ⅲ clinical studies, paclitaxel is mainly applicable to ovarian cancer and breast cancer, and also has certain effects on lung cancer, colorectal cancer, melanoma, head and neck cancer, lymphoma, and brain tumor.

The production method is the natural product isolated and purified from the bark, wooden roots, leaves, twigs and seedlings of yew, with the highest content in the bark. The scientific name of Taxus chinensis in the Chinese Botanical Records is Taxus chinensis. The plant classification is classified into the following categories: gymnosperms, conifers, taxales, taxaceae, and taxus. Taxaceae includes 5 genera and 23 species, and China has 4 genera, 12 species and 1 variety, which are Taxus tibet or Taxus wallichina Zucc., Taxus yunnanensis, Taxus chinensis var. mairei and Taxus cuspidata. It is distributed in Tibet, Yunnan, Guizhou, Sichuan, Guangxi, Guangdong, Hunan, Hubei, Jiangxi, Fujian, Zhejiang, Anhui, Henan, Shanxi, Shaanxi, Gansu and Jilin mountainous areas. It is extracted from the bark or leaves of taxus. Taxus bark or leaves are dried in the shade, ground, and extracted with 95% ethanol. The extract is concentrated to dry, and the residue is mixed with water and dichloromethane. The organic layer is separated by standing, and the water layer is extracted with dichloromethane for many times. The extract and the organic layer are combined and concentrated to dry. The residue is dissolved in ethyl acetate-methanol (3:1), mixed with fresh diatomite, and then evaporated under reduced pressure to remove the solvent. The remaining powder is subjected to rapid column chromatography, first washed with hexane chemicalbook, and then eluted with dichloromethane. Collect the latter and evaporate dichloromethane under reduced pressure. The residue is dissolved in ethyl acetate, and is chromatographed with 70 sets (3~4 pieces per set) of medium-pressure fast chromatographic columns containing silica gel, and eluted with different proportions of hexane-acetone. Collect the components containing products and concentrate them. The residue was purified by a medium-pressure fast chromatographic column containing silica gel and eluted with methanol-dichloromethane of different proportions. Collect the components containing products and concentrate them under reduced pressure. The residue was separated by preparative high performance liquid chromatography, and the obtained product was recrystallized twice with aqueous methanol to obtain pure paclitaxel. Yield: bark 0.028%, leaves 0.0088%. Yield: bark 93.3%, leaves 88%. Melting point 212~214 ℃[ α] D20-49 ° (1%, chloroform). The stem bark of Taxus chinensis was crushed, dried in the shade, soaked in 1% citric acid aqueous solution for 24h, and then began to percolate. The percolate is extracted with dichloromethane, the extract is dried, concentrated, and vacuumed. The silica gel was used for two column chromatography, and the collected effluent contained paclitaxel and harringtonine. Based on their different side chain structures, they are dissolved in carbon tetrachloride and added with bromine. Only harringtonine is brominated. After silica gel column chromatography, the effluent containing only paclitaxel can be obtained. After treatment, high-quality paclitaxel can be obtained, with a content of 99.19% and a yield of 4.5 × 10-5, recovery rate 70%.

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