SEMI-SYNTHESIS OF TAXANE INTERMEDIATES AND THEIR CONVERSION TO PACLITAXEL AND DOCETAXEL

摘要

The invention relates to a process for preparing paclitaxel or docetaxel from9-dihydro-13-acetylbaccatin III, the process comprising the steps of:protecting the hydroxygroup at the C-7 position of the 9-dihydro-13-acetylbaccatin III to yield afirst C-7 protected9-dihydro-13-acetylbaccatin III derivative; oxidizing the hydroxy group at theC-9 position ofthe first C-7 protected 9-dihydro-13-acetylbaccatin III derivative to yield asecond C-7protected 13-acetylbaccatin III derivative; cleaving the ester linkage at, andattaching a sidechain to, the C-13 position of the second C-7 protected 13-acetylbaccatin IIIderivative toyield a C-13 protected taxane intermediate; and converting the C-13 protectedtaxaneintermediate to paclitaxel or docetaxel, wherein the step of cleaving theester linkage at, andattaching a side chain to, the C-13 position of the second C-7 protected 13 -acetylbaccatin IIIderivative comprises combining the second C-7 protected 13-acetylbaccatin IIIderivativewith both a base and a precursor to the side chain, and wherein the precursorto the side chainis selected from the group consisting of beta-lactams, oxazolidines andoxazolines. This isshown by way of example in the following scheme:(see above scheme)