3 years ago

Adenylation Activity of Carboxylic Acid Reductases Enables the Synthesis of Amides

Adenylation Activity of Carboxylic Acid Reductases Enables the Synthesis of Amides
Mark S. Dunstan, Nicholas J. Weise, Sabine L. Flitsch, Sasha R. Derrington, Fabio Parmeggiani, Joseph D. Frampton, Alexander J. L. Wood, Daniela Quaglia, Richard C. Lloyd, Nicholas J. Turner, David Leys, Michael A. Hollas
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: Carboxylic acid reductases can be used as biocatalysts for the activation and subsequent amidation of a range of carboxylic acids with primary and secondary amines, as well as ammonia. The enzymes were used to synthesize the anticonvulsant ilepcimide. Key: adenosine triphosphate (ATP), nicotinamide adenine dinucleotide phosphate (NADPH).

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/anie.201707918

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.