BIOCATALYTIC DERACEMIZATION OF 1,4-BENZODIAZEPINES IN THE SYNTHESIS OF ENANTIOMERICALLY PURE SERINE

An efficient stereocontrolled synthesis of (S)-N-Cbz-serine (Cbz = ben zyloxycarbonyl; 12) and of its (R)-enantiomer is reported. Kinetic res olution of the easily available racemic 3-(hydroxymethyl)-1,4-benzodia zepin-2-ones is performed in the key step via acetylation by the immob ilized Mucor miehei lipase (Lipozyme IM) at 60 degrees. This method is characterized by high enantiomer purity (ee's greater than or equal t o 99%) of the intermediary alcohols (+)-8 and (+)-9 and acetates (-)-1 0 and (-)-11, as well as of the final products (S)- and (R)-N-Cbz-seri ne, simple recycling of the biocatalyst, complete recovery of 2-aminob enzophenones (3 and 4) and their recycling into production of 1,4-benz odiazepines, and possibility to selectively racemize 'wrong' enantiome rs of the alcohols 8 and 9 in the presence of Amberlite CG 400.