Synthesis Of Docetaxel

Malignant tumor, also known as cancer, is a main kind of disease, which is threatening human health currently. Docetaxel, N-benzoyl-N-tert-butoxy-10-deacetylase paclitaxel, is a semi-synthetic paclitaxel derivative developed by French Sanofi-Aventis Company. Docetaxel is effective against advanced breast cancer, non small cell lung cancer, ovarian cancer, prostate cancer, liver cancer and gastric cancer, which is currently the most commonly used antitumor drug, and it is one of the most reliable drug for anti tumor activity and treatment. There are two kinds of methods, namely cyclization of five-membered of oxazolidine and lactamization of four-membered, for synthesis of docetaxel in the literature and patents currently. These two kinds of synthesis methods have many disadvantages, which are harsh reaction conditions, more byproducts, more expensive, and difficult to purification. So it is necessary to find a suitable synthetic method.10-deacetylase baccatin â…¢ (10-DAB â…¢), which is the byproduct of the extraction of paclitaxel from taxus, was used as the starting material to react with trichloroethyl chloroformate through esterification reaction, forming carbonyl protection at C7and C10, then secondary esterification was carried out with five-membered of oxazolidine carboxylic acid side chain condensation. Finally, docetaxel was obtained by using dilute acid to hydrolysis the carbonyl protection groups at C7, C10. The method reported in this paper compared with two kinds of synthesis methods in the literature and patents, has the following advantages:low reaction temperature, reduction of the "Three Guarantees" by-product, thereby reducing refining purification difficulty; the side chain and the mother nuclear condensation generating urea, soluble in water, which is easy to be washed and purity; five-membered side chain ring opening, adopt a more moderate p-toluene sulfonic acid ring opening, less one step of reaction. This synthesis method has the advantages of moderate reaction conditions, easily available raw materials, easily purification, high yield, low cost and suitable for industrial production.