Patent ID: RE39151

Claim:
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) 3 H), lithium triethoxyaluminum hydride (LiAl(OEt) 3 H) and lithium tripropoxyaluminum hydride (LiAl(OPr) 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.