Study On Synthetic Process Of Docetaxel

Docetaxel is a typical semi-synthesis and structure-modified antitumor drug of taxanes. Taxanes compounds are sourced from the bark and leaves of Taxus celebica, along with high broad efficiency. They have become the first-line drugs of ovarian cancer and breast cancer. Especially, docetaxel possesses higher antitumor activity and lower toxicity than paclitaxel, with highest global sales volume over all anticancer drugs.The dissertation is mainly focused on the synthesis, pilot and scale-up of anhydous docetaxel. The process and crafts to obtain a safe, stable and controllable technique were optimized, together with lower cost and higher quality. At the same time, three important known impurities of docetaxel were prepared.We used10-DABIII as starting material, and chose β-Lactam four-membered ring racemate as side chain. Firstly we protected10-DABIII by Troc-Cl reagent. Secondly C13-OH was activated by n-BuLi to result in its lithium salt transition state. Then a stereoselective esterification reaction could occur between the mother nucleus and β-Lactam plane. Finally, after using Zn powder to remove both protecting groups of mother nucleus and side chain, the crude product was purified by special prep-column chromatography and crystallization procedures. Moreover, the docetaxel degrading impurities through chemical reactions were further confirmed with their reference compounds.