Biocatalytic Approaches to the Synthesis of Enantiomerically Pure Chiral Amines

• Published in: Topics in catalysis Vol. 57; no. 5; pp. 284 - 300
• Main Authors: Ghislieri, Diego, Turner, Nicholas J.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.03.2014
• Subjects: Catalysis; Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Industrial Chemistry/Chemical Engineering; Original Paper; Pharmacy; Physical Chemistry; Monoamine oxidase; Directed evolution; Amine dehydrogenase; Transaminase; Chiral amine; Dynamic kinetic resolution; Lipase; Deracemisation
• ISSN: 1022-5528; 1572-9028
• DOI: 10.1007/s11244-013-0184-1

Enantiomerically pure chiral amines are valuable building blocks for the synthesis of pharmaceutical drugs and agrochemicals. Indeed it is estimated that currently 40 % of pharmaceuticals contain a chiral amine component in their structure. Chiral amines are also widely used as resolving agents for diastereomeric salt crystallization. One of the challenges of preparing chiral amines in enantiomerically pure form is the development of cost-effective and sustainable catalytic methods that are able to address the requirement for the entire range of primary, secondary and tertiary amines. In this review we highlight various biocatalytic strategies that have been developed, particularly those based upon asymmetric synthesis or their equivalent therefore (i.e. dynamic kinetic resolution, deracemisation) in which yields and enantiomeric excesses approaching 100 % can be attained. Particular attention is given to the use of monoamine oxidase (MAO-N) from Aspergillus niger which has been engineered by directed evolution to provide a tool-box of variants which can generate enantiomerically pure primary, secondary and tertiary amines. These MAO-N variants are combined with non-selective chemical reducing agents in deracemisation processes.