Chemoenzymatic asymmetric synthesis of the metallo-β-lactamase inhibitor aspergillomarasmine A and related aminocarboxylic acids

Haigen Fu, Jielin Zhang, Mohammad Saifuddin, Gea Cruiming, Pieter G. Tepper, Gerrit J. Poelarends*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

19 Citations (Scopus)
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Abstract

Metal-chelating aminocarboxylic acids are being used in a broad range of domestic products and industrial applications. With the recent identification of the fungal natural product aspergillomarasmine A as a potent and selective inhibitor of metallo-β-lactamases and a promising co-drug candidate to fight antibiotic-resistant bacteria, the academic and industrial interest in metal-chelating chiral aminocarboxylic acids further increased. Here, we report a biocatalytic route for the asymmetric synthesis of aspergillomarasmine A and various related aminocarboxylic acids from retrosynthetically designed substrates. This synthetic route highlights a highly regio- and stereoselective carbon–nitrogen bond-forming step catalysed by ethylenediamine-N,N′-disuccinic acid lyase. The enzyme shows broad substrate promiscuity, accepting a wide variety of amino acids with terminal amino groups for selective addition to fumarate. We also report a two-step chemoenzymatic cascade route for the rapid diversification of enzymatically prepared aminocarboxylic acids by N-alkylation in one pot. This biocatalytic methodology offers a useful alternative route to difficult aminocarboxylic acid products.
Original languageEnglish
Pages (from-to)186-191
Number of pages6
JournalNature Catalysis
Volume1
Issue number3
DOIs
Publication statusPublished - Mar-2018

Keywords

  • ANTIBIOTIC-RESISTANCE
  • PYRENOPHORA-TERES
  • RETROSYNTHESIS
  • LYASE

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