My watch list
my.chemeurope.com  
Login  

Adenylation Activity of Carboxylic Acid Reductases Enables the Synthesis of Amides

Abstract

Carboxylic acid reductases (CARs) catalyze the reduction of a broad range of carboxylic acids to aldehydes using the cofactors adenosine triphosphate and nicotinamide adenine dinucleotide phosphate, and have become attractive biocatalysts for organic synthesis. Mechanistic understanding of CARs was used to expand reaction scope, generating biocatalysts for amide bond formation from carboxylic acid and amine. CARs demonstrated amidation activity for various acids and amines. Optimization of reaction conditions, with respect to pH and temperature, allowed for the synthesis of the anticonvulsant ilepcimide with up to 96 % conversion. Mechanistic studies using site‐directed mutagenesis suggest that, following initial enzymatic adenylation of substrates, amidation of the carboxylic acid proceeds by direct reaction of the acyl adenylate with amine nucleophiles.

CARpe diem: Carbonsäure‐Reduktasen können als Biokatalysatoren für die Aktivierung und nachfolgende Amidierung einer Reihe von Carbonsäuren mit primären und sekundären Aminen sowie Ammoniak verwendet werden. Die Enzyme fanden Anwendung für die Herstellung von Ilepcimid, einem krampflösenden Mittel. ATP=Adenosintriphosphat, NADPH=Nicotinamid‐Adenin‐Dinucleotid‐Phosphat.

Authors:   Sabine Flitsch, Alexander Wood, Nicholas Weise, Joseph Frampton, Mark Dunstan, Michael Hollas, Sasha Derrington, Richard LLoyd, Daniela Quaglia, Fabio Parmeggiani, David Leys, Nicholas Turner; Alexander J. L. Wood, Nicholas J. Weise, Joseph D. Frampton, Mark S. Dunstan, Michael A. Hollas, Sasha R. Derrington, Richard C. Lloyd, Daniela Quaglia, Fabio Parmeggiani, David Leys, Nicholas J. Turner, Sabine L. Flitsch
Journal:   Angewandte Chemie
Volume:   129
edition:   46
Year:   2017
Pages:   14690
DOI:   10.1002/ange.201707918
Publication date:   13-Oct-2017
More about Angewandte Chemie
  • News

    Polymers with Helical Blocks

    Polymers, the basis of all plastics, usually do not have an ordered structure, in contrast to biopolymers such as proteins. A team of researchers has now developed a polymer that can be differentiated into folded (ordered) and unfolded (disordered) domains using UV irradiation. The team’s w ... more

    Methane from Carbon Dioxide

    Recycling carbon dioxide (CO2), especially through conversion to methane (CH4), is compelling while anthropogenic CO2 emissions are still rising. A useful process for this transformation is photothermal methanation, in which CO2 and hydrogen are catalytically converted into CH4 and water u ... more

    Liquid Fuels from Carbon Dioxide

    A new electrocatalyst called a-CuTi@Cu converts carbon dioxide (CO2 ) into liquid fuels. As reported by a team of Chinese researchers in the journal Angewandte Chemie, active copper centered on an amorphous copper/titanium alloy produces ethanol, acetone, and n-butanol with high efficiency. ... more

More about Wiley
Your browser is not current. Microsoft Internet Explorer 6.0 does not support some functions on Chemie.DE