Abstract
Asymmetric reductive aminations are some of the most important reactions in the preparation of active pharmaceuticals, as chiral amines feature in many of the world's most important drugs. Although many enzymes have been applied to the synthesis of chiral amines, the development of reductive amination reactions that use enzymes is attractive, as it would permit the one-step transformation of readily available prochiral ketones into chiral amines of high optical purity. However, as most natural “reductive aminase” activities operate on keto acids, and many are able to use only ammonia as the amine donor, there is considerable scope for the engineering of natural enzymes for the reductive amination of ketones, and also for the preparation of secondary amines using alkylamines as donors. This review summarises research into the development of NAD(P)H-dependent dehydrogenases for the reductive amination of ketones, including amino acid dehydrogenases (AADHs), natural amine dehydrogenases (AmDHs), opine dehydrogenases (OpDHs) and imine reductases (IREDs). In each case knowledge of the structure and mechanism of the enzyme class is addressed, with a further description of the engineering of those enzymes for the reductive amination of ketones towards primary and also secondary amine products. (Figure presented.).
| Original language | English |
|---|---|
| Pages (from-to) | 2011-2025 |
| Number of pages | 16 |
| Journal | Advanced Synthesis and Catalysis |
| Volume | 359 |
| Issue number | 12 |
| Early online date | 11 May 2017 |
| DOIs | |
| Publication status | Published - 19 Jun 2017 |
Bibliographical note
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details.Keywords
- amination
- amine dehydrogenase
- enzyme catalysis
- imine reductase
- oxidoreductases
- reductive amination