Asymmetric synthesis of primary amines catalyzed by thermotolerant fungal reductive aminases.

Chemical Science
Juan Mangas-SanchezNicholas J Turner

Abstract

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. (NfRedAm and NfisRedAm) 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 NfRedAm and NfisRedAm highlight their pote...Continue Reading

References

Jan 24, 2008·Chembiochem : a European Journal of Chemical Biology·Matthias HöhneUwe T Bornscheuer
Sep 8, 2011·Bioscience, Biotechnology, and Biochemistry·Koichi MitsukuraToru Nagasawa
Mar 8, 2012·Angewandte Chemie·Michael J AbrahamsonAndreas S Bommarius
Jul 6, 2014·Chemical Communications : Chem Comm·K Engelmark CassimjeeJ-E Bäckvall
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Jul 1, 2017·Green Chemistry : an International Journal and Green Chemistry Resource : GC·Tanja KnausFrancesco G Mutti
Sep 25, 2017·Nature Chemistry·Godwin A AlekuNicholas J Turner
Nov 4, 2017·Current Opinion in Chemical Biology·Gideon Grogan
Jun 21, 2018·Chemical Society Reviews·Joshua BrittonGregory A Weiss

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Citations

Aug 31, 2021·RSC Chemical Biology·Mélanie Hall
Nov 3, 2021·Chembiochem : a European Journal of Chemical Biology·Jack J SangsterJuan Mangas-Sanchez

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Methods Mentioned

BETA
light scattering
circular dichroism
thermal treatment

Software Mentioned

DALI

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