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Biocatalytic Deracemization of 1,4‐Benzodiazepines in the Synthesis of Enantiomerically Pure Serine
Author(s) -
Avdagić Amir,
Šunjić Vitomir
Publication year - 1998
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19980810110
Subject(s) - chemistry , kinetic resolution , enantiomer , biocatalysis , lipase , hydroxymethyl , serine , organic chemistry , enantiomeric excess , candida antarctica , enantioselective synthesis , enzyme , catalysis , reaction mechanism
An efficient stereocontrolled synthesis of ( S )‐ N ‐Cbz‐serine (Cbz = benzyloxycarbonyl; 12 ) and of its ( R )‐enantiomer is reported. Kinetic resolution of the easily available racemic 3‐(hydroxymethyl)‐1,4‐benzodiazepin‐2‐ones is performed in the key step via acetylation by the immobilized Mucor miehei lipase ( Lipozyme IM ) at 60°. This method is characterized by high enantiomer purity (ee's ges; 99%) of the intermediary alcohols (+)‐ 8 and (+)‐ 9 and acetates (−)‐ 10 and (−)‐ 11 , as well as of the final products ( S )‐ and ( R )‐ N ‐Cbz‐serine, simple recycling of the biocatalyst, complete recovery of 2‐aminobenzophenones ( 3 and 4 ) and their recycling into production of 1,4‐benzodiazepines, and possibility to selectively racemize ‘wrong’ enantiomers of the alcohols 8 and 9 in the presence of Amberlite CG 400 .