Semisynthesis Of New Anticancer Drug, Taxol

Taxol is a natural compound with unique antitumor mechamism of action, it is also one of the most promising antitumor drugs. This compound which has strong anticancer properties with particularly significant activity against several human tumors has received much attention as chemotherapeutic agent. Then the unique action of Taxol spurred an increase in the chemical and biological studies of the Taxol, and which produced by semisynthesis was approved for use by the U.S. Food and Drug Administration (FDA) on Dec. 1994.The article had reported the synthesis of Taxol C13 side chain from cinnammic acid for the first time. Epoxycinnammic acid prepared from cinnammic acid was resolved by R-α-phenylethylamine to giveβ-epoxycinnammic acid R-α-phenylethylamine salt, and then coverted to potassium salt. Thisβ-epoxycinnammic potassium salt reacting with sodium azide was acidified to give azidoacid, and then esterified with 4M HCl/MeOH. Azido group of the intermediate was reduced with Zn/NH4Cl, bezoylated with benzoic chloride to furnished 2S-hydroxyl-3S -N-benzoylaminophenylpropanoic acid methyl ester, and which was treated with mesyl chloride in pyridine and then treated with LiOH in THF to give Taxol C13 side chain (4S-trans)-4,5-Dihydro-2,4-diphenyl -5-oxazolecarboxylic acid .The semi-synthesis was completed by coupling of hydroxyl group and carboxyl group at the 13-position of the natural precursor, 10-deacetyl baccatinⅢ(10-DABⅢ). 10-DAB was converted to 7-triethylsilyl 10-deacetylbaccatinⅢ, and then acetylated to give 7-triethylsilyl baccatinⅢ, which was then coupled with the commercially available side chain N-benzoyl-(2R, 3S)-phenylisoserine in the presence of DCC and DMAP. Removal of the protecting group with 5% HCl gave Taxol in high yield.The article do the research of the preparation of Taxol C13 side chain with newmaterial and new route, the whole process possesses such advantages as facile material, mild condition, simple operation and cheap cost, which provides a new approach and method for the semisynthesis of Taxol.