Mechanistic considerations pertaining to the solvolysis of paclitaxel analogs bearing ester groups at the C2 ' position

Dilute solutions of paclitaxel-related derivatives having chloroacetyl este rs in the CT position undergo ready methanolysis according to pseudo first- order kinetics while more concentrated solutions appear to be stabilized, p ossibly by the formation of hydrophobic aggregates that tend to bury this r eaction center. Methanolysis is also attenuated in the presence of weak aci d, suggesting that paclitaxel's neighboring benzamide nitrogen may be parti cipating in the reaction by serving as an assisting nucleophile. (C) 2001 E lsevier Science Ltd. All rights reserved.