Anticancer taxanes such as paclitaxel, docetaxel and their structural analogs, and a method for the preparation thereof

摘要

A process for the preparation of taxanes comprising wherein R is a tert. butoxycarbonyl or benzoyl group; PMP is p-methoxyphenyl group; G1 is acetyl group; G2 is haloacetyl group comprising a) protecting the C-7 hydroxyl group of 10-deacetylbaccatin III with haloacetyl chlorides and then acetylating the C-10 hydroxyl group with acetyl chloride to obtain a protected 10-deacetylbaccatin III (1); b) subjecting the protected 10-deacetylbaccatin III (1) to coupling with an oxazolidine-5-caboxylic acid of formula 2 wherein R is tert. butoxycarbonyl or benzoyl; PMP is p-methoxyphenyl group in the presence of a condensation agent and an activating agent to obtain C-13 esters of formula 3; c) treating the coupled products 3 with weak acidic medium to open the oxazolidine ring to obtain intermediates of formula 4; wherein R is a tert. butoxycarbonyl or benzoyl group; G1 is acetyl group; G2 is haloacetyl group d) subjecting the intermediates of compound 4 to selective deprotection of haloacyl group in the presence of acetyl group under mild alkaline condition at -20 to +40° C. for 6-24h in the presence of ammonia or aliphatic amine or aromatic amines or their combination to obtain paclitaxel or docetaxel.