中文同义词: 多烯他赛; ;紫杉特尔;多希紫杉醇;多烯紫杉醇
Docetaxel Basic information
Product Name: Docetaxel
Synonyms:N-debenzoyl-N-tert-butoxycarbonyl-10-deacetyl taxol; Taxotere
Melting point: 186-192 °C (dec.)
Properties: white Cryst
Usage: antineoplastic;binds to microtubules
Docetaxel belongs to taxanes-class drugs. It can boost the assembly of tubulin dimer into microtubules while stabilizing the microtubules by preventing the process of de-polymerization. Owing to the above two effects, it block the cells in the G2 and M phase, and thereby inhibiting cancer cell mitosis and proliferation. The pharmacological effect of docetaxel is higher than paclitaxel with former one having an intracellular concentration 3-fold of the later one. It also has a long retention time inside the cell and has a microtubule affinity twice of that of paclitaxel. As a microtubule-stabilizing agents and assembly accelerator, it has a 2 times larger activity than paclitaxel. As a microtubule depolymerization inhibitor, its activity is also 2 times larger than that of paclitaxel. In the in vitro tests of anti-tumor activity, it has been confirmed that the anti-tumor activity docetaxel is 1.3 to 12 times as high as paclitaxel. Clinical studies show that docetaxel has a much better efficacy than paclitaxel in treating the anthracycline-resistant breast cancer.
Semi-synthesis of it uses the 10-deacetylbaccatin III as raw materials extracted from the needle-like leaves of the European yew Taxus baccata L. 10-deacetylbaccatin III can be converted to the compound product (I) after acylation.
Cinnamic acid (330mg, 2.24mmo1), dicyclohexyl carbodiimide (DCC, 460mg, 2.24mmo1), the compound (I) (500mg, 0.56mmo1) and 4-dimethylaminopyridine (68mg, 0.56mmo1) are stirred under argon at 70 °C for 15h. Cooled, filtered, and the filter pellet should be further washed with toluene. Combine the filtrate and washings and concentrate under reduced pressure. Add methylene chloride to the residue; wash with 2% aqueous hydrochloric acid; dry it using anhydrous magnesium sulfate. The solvent is further evaporated under reduced pressure, and the remaining 1g residue is purified by column chromatography with the elution of hexane - ethyl acetate (7: 3) to obtain 540mg compound (II), yield 94%.