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

Dilute solutions of paclitaxel-related derivatives having chloroacetyl esters in the C2′ position undergo ready methanolysis according to pseudo first-order kinetics while more concentrated solutions appear to be stabilized, possibly by the formation of hydrophobic aggregates that tend to bury this reaction center. Methanolysis is also attenuated in the presence of weak acid, suggesting that paclitaxelʹs neighboring benzamide nitrogen may be participating in the reaction by serving as an assisting nucleophile.