Enzymatic resolution of racemic amines in a continuous reactor in organic solvents
Article first published online: 19 FEB 2004
Copyright © 1992 John Wiley & Sons, Inc.
Biotechnology and Bioengineering
Volume 40, Issue 7, pages 760–767, 5 October 1992
How to Cite
Gutman, A. L., Meyer, E., Kalerin, E., Polyak, F. and Sterling, J. (1992), Enzymatic resolution of racemic amines in a continuous reactor in organic solvents. Biotechnol. Bioeng., 40: 760–767. doi: 10.1002/bit.260400703
- Issue published online: 19 FEB 2004
- Article first published online: 19 FEB 2004
- Manuscript Accepted: 29 APR 1992
- Manuscript Received: 3 JAN 1992
- organic solvent;
- stereoselective aminolysis;
- immobilized enzyme;
- continuous process
An enzymatic process has been developed for the continuous production of the pharmaceutically important intermediate (R)-1-aminoindan and of the chiral resolving agent (R)-1-(1-naphthyl)ethylamine. The process consists of the subtilisin catalyzed stereoselective aminolysis of the racemic primary amine with an active ester in organic solvent. The competing nonenzymatic reaction has been suppressed by appropriate choice of solvent and reactant's concentration and by minimizing the time of contact between the amine and the active ester. Subtilisin was immobilized on glass beads and the reaction carried out in a continuous-flow column bioreactor. By using a 450-mL column bioreactor containing 5.7 g of subtilisin immobilized on 570 g of glass beads, 1.6 kg of racemic 1-(1-naphthyl)ethylamine was resolved after 320 h of continuous operation with only a slight loss of the enzymatic activity. During the whole process, the optical purity of the chiral amine eluting from the column was higher than 90%. A facile procedure was developed for separating the unreacted (R)-amine from the (S)-amide and for the recycling of the solvent 3-methyl-3-pentanol and the active ester 2,2,2-trifluoroethyl butyrate. © 1992 John Wiley & Sons, Inc.