Abstract
N-arylated α-amino acids and pyrazolidin-3-ones are widely being used as chiral building blocks for pharmaceuticals and agrochemicals. Here we report a biocatalytic route for the asymmetric synthesis of various N-arylated aspartic acids applying ethylenediamine-N,N'-disuccinic acid lyase (EDDS lyase) as biocatalyst. This enzyme shows a broad substrate scope, enabling the addition of a variety of arylamines to fumarate with high conversions, yielding the corresponding N-arylated aspartic acids in good isolated yields and with high enantiomeric excess (ee >99%). Furthermore, we developed a chemoenzymatic method towards synthetically challenging chiral 2-aryl-5-carboxylpyrazolidin-3-ones, using arylhydrazines as bisnucleophilic donors in the EDDS lyase-catalyzed hydroamination of fumarate followed by an acid-catalyzed intramolecular amidation, achieving good overall yields and high optical purity (ee >99%). In addition, we successfully combined the EDDS lyase-catalyzed hydroamination and acid-catalyzed cyclization steps in one pot, thus providing a simple chemoenzymatic cascade route for synthesis of enantiomerically pure pyrazolidin-3-ones. Hence, these biocatalytic methods provide convenient alternative routes to important chiral N-arylated aspartic acids and difficult 2-aryl-5-carboxylpyrazolidin-3-ones.
Original language | English |
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Pages (from-to) | 7292-7299 |
Number of pages | 8 |
Journal | ACS Catalysis |
Volume | 9 |
Issue number | 8 |
DOIs | |
Publication status | Published - 2-Aug-2019 |
Keywords
- Asymmetric synthesis
- biocatalysis
- EDDS lyase
- unnatural amino acids
- pyrazolidinones
- cascade synthesis
- ASPARTIC ACIDS
- ENANTIOSELECTIVE SYNTHESIS
- 1,3-DIPOLAR CYCLOADDITION
- KINETIC RESOLUTION
- AZOMETHINE IMINES
- DEHYDROGENASE
- MECHANISMS
- ARYLATION
- PEPTIDES
- HALIDES