Synthesis And Purification Of Docetaxel

Docetaxel, namely N-benzoyl-N-t-Boc-10-to acetyl paclitaxel, is a semi-synthetic paclitaxel derivatives development of French Sanofi-Aventis, for advanced breast cancer, non-small cell lung cancer, ovarian cancer, prostate cancer, pancreatic cancer, liver cancer, gastric cancer, head and neck cancer have the effect.2004September docetaxel injection was selected in the2004version of "national essential drug preparations" and "catalogue of national basic medical insurance and industrial injury insurance drug list", into the health insurance directory, the rapid growth of docetaxel sales scale, has become the market sales of the largest antitumor drugs.10-DAB III, the starting material, esterified with trichloro-ethoxycarbonyl chloride to protect C-7,C-10oxycarbonyl of10-DAB III, form7,10-bis(2,2,2-trichlore-ethoxycarbonyl carbonyl)-10-DAB III,and then condensed with1-tert-butoxycarbonyl-3-triethyl silicon-4-phenyl-2-acridone in the C-13to form2-(triethyl silicon)-7,10-(2,2,2-trichloro-ethoxycarbonyl)docetaxel. Then taken off the C-7,C-10and C-13side chain protecting group under the condition of acetic acid-water-zinc-hydrochloric acid, received docetaxel crude. Using ethyl acetate-petroleum ether as eluent, separated by column chromatography on docetaxel crude, and finally with ethanol-water of crystallization obtained docetaxel trihydrate. The synthetic methods mainly include the parent nuclear protection, side chain and the core link, the mother nucleus deprotection of three step reaction. The reaction solvent is toxicity and easy, mild reaction conditions, suitable for industrial production. The crystal form of docetaxel trihydrate is quality and stability, convenient for storage.