Biocatalytic Reductive Amination by Native Amine Dehydrogenases to Access Short Chiral Alkyl Amines and Amino Alcohols
نویسندگان
چکیده
Small optically active molecules, and more particularly short-chain chiral amines, are key compounds in the chemical industry precursors of various pharmaceuticals. Their chemo-biocatalytic production on a commercial scale is already established, mainly through lipase-catalyzed resolutions leading to ChiPros™ products among others. Nevertheless, their biocatalytic synthesis remains challenging for very C4 C5 amines due low enantiomeric excess. To complement possibilities recently offered by transaminases, this work describes alternative access using amine dehydrogenases (AmDHs). Without any protein engineering, some described wild-type AmDHs ( Cfus AmDH, Msme Micro MATOUAmDH2) were shown be efficient hydroxylated or unfunctionalized small 2-aminoalkanes. Conversions up 97.1% reached at 50 mM, moderate high enantioselectivities obtained, especially S )-1-methoxypropan-2-amine (98.1%), )-3-aminobutan-1-ol (99.5%), (3 )-3-aminobutan-2-ol (99.4%), )-butan-2-amine (93.6%) with AmDH. Semi-preparative scale-up experiments successfully performed 150 mM substrate concentrations )-1-methoxypropan-2-amine, latter known as “( )-MOIPA”. Modeling studies provided preliminary results explaining basis discrimination between similarly sized substituents sites these enzymes.
منابع مشابه
Amine dehydrogenases: efficient biocatalysts for the reductive amination of carbonyl compounds
Amines constitute the major targets for the production of a plethora of chemical compounds that have applications in the pharmaceutical, agrochemical and bulk chemical industries. However, the asymmetric synthesis of α-chiral amines with elevated catalytic efficiency and atom economy is still a very challenging synthetic problem. Here, we investigated the biocatalytic reductive amination of car...
متن کاملFrom Racemic Alcohols to Enantiopure Amines: Ru-Catalyzed Diastereoselective Amination
A commercially available ruthenium(II) PNP-type pincer catalyst (Ru-Macho) promotes the formation of α-chiral tert-butanesulfinylamines from racemic secondary alcohols and Ellman's chiral tert-butanesulfinamide via a hydrogen borrowing strategy. The formation of α-chiral tert-butanesulfinylamines occurs in yields ranging from 31% to 89% with most examples giving >95:5 dr.
متن کاملIn situ approach for testing the enantiopurity of chiral amines and amino alcohols by 1H NMR.
An in situ approach involving a simple mix and shake method for testing the enantiopurity of primary, secondary and tertiary chiral amines and their derivatives, chiral amino alcohols, by (1)H-NMR spectroscopy is developed. The protocol involves the in situ formation of chiral ammonium borate salt from a mixture of C2 symmetric chiral BINOL, trialkoxyborane and chiral amines. The proposed conce...
متن کاملEnantioselective organocatalytic reductive amination.
The first enantioselective organocatalytic reductive amination reaction has been accomplished. The development of a new chiral phosphoric acid catalyst has provided a convenient strategy for the enantioselective construction of protected primary amines and provided a highly stereoselective method for the reductive amination of heterocyclic amines. A diverse spectrum of ketone and amine substrat...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Frontiers in catalysis
سال: 2021
ISSN: ['2673-7841']
DOI: https://doi.org/10.3389/fctls.2021.781284