Asymmetric synthesis of primary amines catalyzed by thermotolerant fungal reductive aminases

Chiral primary amines are important intermediates in the synthesis of pharmaceutical compounds. Fungal reductive aminases (RedAms) are NADPH-dependent dehydrogenases that catalyse reductive amination of a range of ketones with short-chain primary amines supplied in an equimolar ratio to give corresp...

Full description

Saved in:
Bibliographic Details
Published in:Chemical science (Cambridge) 2020-05, Vol.11 (19), p.552-557
Main Authors: Mangas-Sanchez, Juan, Sharma, Mahima, Cosgrove, Sebastian C, Ramsden, Jeremy I, Marshall, James R, Thorpe, Thomas W, Palmer, Ryan B, Grogan, Gideon, Turner, Nicholas J
Format: Article
Language:English
Subjects:
Amines
Ammonia
Chemical synthesis
Chemistry
Enzymes
Fungi
Homology
Ketones
Temperature dependence
Thermal stability
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Chiral primary amines are important intermediates in the synthesis of pharmaceutical compounds. Fungal reductive aminases (RedAms) are NADPH-dependent dehydrogenases that catalyse reductive amination of a range of ketones with short-chain primary amines supplied in an equimolar ratio to give corresponding secondary amines. Herein we describe structural and biochemical characterisation as well as synthetic applications of two RedAms from Neosartorya spp. ( Nf RedAm and Nfis RedAm) that display a distinctive activity amongst fungal RedAms, namely a superior ability to use ammonia as the amine partner. Using these enzymes, we demonstrate the synthesis of a broad range of primary amines, with conversions up to >97% and excellent enantiomeric excess. Temperature dependent studies showed that these homologues also possess greater thermal stability compared to other enzymes within this family. Their synthetic applicability is further demonstrated by the production of several primary and secondary amines with turnover numbers (TN) up to 14 000 as well as continous flow reactions, obtaining chiral amines such as ( R )-2-aminohexane in space time yields up to 8.1 g L −1 h −1 . The remarkable features of Nf RedAm and Nfis RedAm highlight their potential for wider synthetic application as well as expanding the biocatalytic toolbox available for chiral amine synthesis. Fungal reductive aminases as effective biocatalysts for the preparation of chiral primary amines.
ISSN:2041-6520
2041-6539
DOI:10.1039/d0sc02253e