Patent ID: 6333410
Filing Date: 2001-12-25
Classification: A61K,A61P,C07D

Abstract:
A process for preparing a thiol-containing maytansinoid wherein the thiol group is part of the ester moiety at C-3, comprising the steps of:(1) conducting reductive hydrolysis of a maytansinoid C-3 ester with a reducing agent selected from the group consisting of lithium trimethoxyaluminum hydride (LiAl(OMe).sub.3 H), lithium triethoxyaluminum hydride (LiAl(OEt).sub.3 H) and lithium tripropoxyaluminum hydride (LiAl(OPr).sub.3 H), to yield a maytansinol;(2) purifying the maytansinol to remove side products when present;(3) esterifying the purified maytansinol with a carboxylic acid to yield a reaction mixture of an L- and a D-aminoacyl ester of maytansinol;(4) separating the L-aminoacyl ester of maytansinol from the reaction mixture in (3);(5) reducing the L-aminoacyl ester of maytansinol to yield a thiol-containing maytansinoid; and(6) purifying the thiol-containing maytansinoid.