Browse
Submit Data
Databases
API
Help

Dataset Information

26 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Conversion of alcohols to enantiopure amines through dual-enzyme hydrogen-borrowing cascades.

ABSTRACT: ?-Chiral amines are key intermediates for the synthesis of a plethora of chemical compounds at industrial scale. We present a biocatalytic hydrogen-borrowing amination of primary and secondary alcohols that allows for the efficient and environmentally benign production of enantiopure amines. The method relies on a combination of two enzymes: an alcohol dehydrogenase (from Aromatoleum sp., Lactobacillus sp., or Bacillus sp.) operating in tandem with an amine dehydrogenase (engineered from Bacillus sp.) to aminate a structurally diverse range of aromatic and aliphatic alcohols, yielding up to 96% conversion and 99% enantiomeric excess. Primary alcohols were aminated with high conversion (up to 99%). This redox self-sufficient cascade possesses high atom efficiency, sourcing nitrogen from ammonium and generating water as the sole by-product.

SUBMITTER: Mutti FG

PROVIDER: S-EPMC4883652 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Conversion of alcohols to enantiopure amines through dual-enzyme hydrogen-borrowing cascades.

Mutti Francesco G FG Knaus Tanja T Scrutton Nigel S NS Breuer Michael M Turner Nicholas J NJ

Science (New York, N.Y.) 20150901 6255

α-Chiral amines are key intermediates for the synthesis of a plethora of chemical compounds at industrial scale. We present a biocatalytic hydrogen-borrowing amination of primary and secondary alcohols that allows for the efficient and environmentally benign production of enantiopure amines. The method relies on a combination of two enzymes: an alcohol dehydrogenase (from Aromatoleum sp., Lactobacillus sp., or Bacillus sp.) operating in tandem with an amine dehydrogenase (engineered from Bacillu ...[more]

PMID: 26404833

Similar Datasets

Mimicking transition metals in borrowing hydrogen from alcohols.

Project description:Borrowing hydrogen from alcohols, storing it on a catalyst and subsequent transfer of the hydrogen from the catalyst to an in situ generated imine is the hallmark of a transition metal mediated catalytic N-alkylation of amines. However, such a borrowing hydrogen mechanism with a transition metal free catalytic system which stores hydrogen molecules in the catalyst backbone is yet to be established. Herein, we demonstrate that a phenalenyl ligand can imitate the role of transition metals in storing and transferring hydrogen molecules leading to borrowing hydrogen mediated alkylation of anilines by alcohols including a wide range of substrate scope. A close inspection of the mechanistic pathway by characterizing several intermediates through various spectroscopic techniques, deuterium labelling experiments, and DFT study concluded that the phenalenyl radical based backbone sequentially adds H+, H˙ and an electron through a dearomatization process which are subsequently used as reducing equivalents to the C-N double bond in a catalytic fashion.

| S-EPMC8221061 | biostudies-literature

Cyclometalated Iridium Complex-Catalyzed <i>N</i>-Alkylation of Amines with Alcohols via Borrowing Hydrogen in Aqueous Media.

Project description:This paper develops a methodology for cyclometalated iridium complex-catalyzed N-alkylation of amines with alcohols via borrowing hydrogen in the aqueous phase. The cyclometalated iridium catalyst-mediated N-alkylation of amines with alcohols displays high activity (S/C up to 10,000 and yield up to 96%) and ratio of amine/imine (up to >99:1) in a broad range of substrates (up to 46 examples) using water as the green and eco-friendly solvent. Most importantly, this transformation is simple, efficient, and can be performed at a gram scale, showcasing its potential for industrially synthesizing N-alkylamine compounds.

| S-EPMC7594325 | biostudies-literature

From racemic alcohols to enantiopure amines: Ru-catalyzed diastereoselective amination.

Project description: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.

| S-EPMC4160272 | biostudies-literature

Iron-Catalyzed Borrowing Hydrogen ?-C(sp3)-Methylation of Alcohols.

Project description:Herein we report the iron-catalyzed ?-C(sp3)-methylation of primary alcohols using methanol as a C1 building block. This borrowing hydrogen approach employs a well-defined bench-stable (cyclopentadienone)iron(0) carbonyl complex as precatalyst (5 mol %) and enables a diverse selection of substituted 2-arylethanols to undergo ?-C(sp3)-methylation in good isolated yields (24 examples, 65% average yield).

| S-EPMC7011770 | biostudies-literature

Ruthenium-Catalyzed Amination of Secondary Alcohols using Borrowing Hydrogen Methodology.

Project description:A new ruthenium complex catalyzes the amination of primary and secondary alcohols and the regioselective mono- and sequential diamination of diols via the borrowing hydrogen pathway. Several variations on new intra- and intermolecular cyclizations of aminoalcohols, diols and diamines lead to heterocyclic ring systems.

| S-EPMC5604847 | biostudies-literature

Iron-Catalyzed Borrowing Hydrogen C-Alkylation of Oxindoles with Alcohols.

Project description:A general and efficient iron-catalyzed C-alkylation of oxindoles has been developed. This borrowing hydrogen approach employing a (cyclopentadienone)iron carbonyl complex (2 mol %) exhibited a broad reaction scope, allowing benzylic and simple primary and secondary aliphatic alcohols to be employed as alkylating agents. A variety of oxindoles underwent selective mono-C3-alkylation in good-to-excellent isolated yields (28 examples, 50-92 % yield, 79 % average yield).

| S-EPMC6619250 | biostudies-literature

Dual catalysis for enantioselective convergent synthesis of enantiopure vicinal amino alcohols.

Project description:Enantiopure vicinal amino alcohols and derivatives are essential structural motifs in natural products and pharmaceutically active molecules, and serve as main chiral sources in asymmetric synthesis. Currently known asymmetric catalytic protocols for this class of compounds are still rare and often suffer from limited scope of substrates, relatively low regio- or stereoselectivities, thus prompting the development of more effective methodologies. Herein we report a dual catalytic strategy for the convergent enantioselective synthesis of vicinal amino alcohols. The method features a radical-type Zimmerman-Traxler transition state formed from a rare earth metal with a nitrone and an aromatic ketyl radical in the presence of chiral N,N'-dioxide ligands. In addition to high level of enantio- and diastereoselectivities, our synthetic protocol affords advantages of simple operation, mild conditions, high-yielding, and a broad scope of substrates. Furthermore, this protocol has been successfully applied to the concise synthesis of pharmaceutically valuable compounds (e.g., ephedrine and selegiline).

| S-EPMC5789022 | biostudies-literature

Efficient synthesis of enantiopure amines from alcohols using resting <i>E. coli</i> cells and ammonia.

Project description:α-Chiral amines are pivotal building blocks for chemical manufacturing. Stereoselective amination of alcohols is receiving increased interest due to its higher atom-efficiency and overall improved environmental footprint compared with other chemocatalytic and biocatalytic methods. We previously developed a hydrogen-borrowing amination by combining an alcohol dehydrogenase (ADH) with an amine dehydrogenase (AmDH) in vitro. Herein, we implemented the ADH-AmDH bioamination in resting Escherichia coli cells for the first time. Different genetic constructs were created and tested in order to obtain balanced expression levels of the dehydrogenase enzymes in E. coli. Using the optimized constructs, the influence of several parameters towards the productivity of the system were investigated such as the intracellular NAD+/NADH redox balance, the cell loading, the survival rate of recombinant E. coli cells, the possible toxicity of the components of the reaction at different concentrations and the influence of different substrates and cosolvents. In particular, the cofactor redox-balance for the bioamination was maintained by the addition of moderate and precise amounts of glucose. Higher concentrations of certain amine products resulted in toxicity and cell death, which could be alleviated by the addition of a co-solvent. Notably, amine formation was consistent using several independently grown E. coli batches. The optimized E. coli/ADH-AmDH strains produced enantiopure amines from the alcohols with up to 80% conversion and a molar productivity up to 15 mM. Practical applicability was demonstrated in a gram-scale biotransformation. In summary, the present E. coli-ADH-AmDH system represents an important advancement towards the development of 'green', efficient and selective biocatalytic processes for the amination of alcohols.

| S-EPMC7116806 | biostudies-literature

Hydrogen-Borrowing Alkylation of 1,2-Amino Alcohols in the Synthesis of Enantioenriched γ-Aminobutyric Acids.

Project description:For the first time we have been able to employ enantiopure 1,2-amino alcohols derived from abundant amino acids in C-C bond-forming hydrogen-borrowing alkylation reactions. These reactions are facilitated by the use of the aryl ketone Ph*COMe. Racemisation of the amine stereocentre during alkylation can be prevented by the use of sub-stoichiometric base and protection of the nitrogen with a sterically hindered triphenylmethane (trityl) or benzyl group. The Ph* and trityl groups are readily cleaved in one pot to give γ-aminobutyric acid (GABA) products as their HCl salts without further purification. Both steps may be performed in sequence without isolation of the hydrogen-borrowing intermediate, removing the need for column chromatography.

| S-EPMC8048514 | biostudies-literature

Hydrogen-borrowing and interrupted-hydrogen-borrowing reactions of ketones and methanol catalyzed by iridium.

Project description:Reported herein is the use of catalytic [{Ir(cod)Cl}2 ] to facilitate hydrogen-borrowing reactions of ketone enolates with methanol at 65?°C. An oxygen atmosphere accelerates the process, and when combined with the use of a bulky monodentate phosphine ligand, interrupts the catalytic cycle by preventing enone reduction. Subsequent addition of pro-nucleophiles to the reaction mixture allowed a one-pot methylenation/conjugate addition protocol to be developed, which greatly expands the range of products that can be made by this methodology.

| S-EPMC4344817 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data