School of Chemistry

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Browsing School of Chemistry by Author "Abidin, Mohammad Z."
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    Biocatalytic enantioselective hydroaminations enabling synthesis ofN-arylalkyl-substitutedl-aspartic acids
    ( 2021-08-07) Abidin, Mohammad Z. ; Saravanan, Thangavelu ; Bothof, Laura ; Tepper, Pieter G. ; Thunnissen, Andy Mark W.H. ; Poelarends, Gerrit J.
    N-Substitutedl-aspartic acids are important chiral building blocks for pharmaceuticals and food additives. Here we report the asymmetric synthesis of variousN-arylalkyl-substitutedl-aspartic acids using ethylenediamine-N,N′-disuccinic acid lyase (EDDS lyase) as a biocatalyst. This C-N lyase shows a broad non-natural amine substrate scope and outstanding enantioselectivity, allowing the efficient addition of structurally diverse arylalkylamines to fumarate to afford the correspondingN-arylalkyl-substitutedl-aspartic acids in good isolated yield (up to 79%) and with excellent enantiopurity ( > 99% ee). These results further demonstrate that C-N lyases working in reverse constitute an extremely powerful synthetic tool to prepare difficult noncanonical amino acids.
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    Modular Enzymatic Cascade Synthesis of Vitamin B < inf > 5 < /inf > and Its Derivatives
    ( 2018-11-27) Abidin, Mohammad Z. ; Saravanan, Thangavelu ; Zhang, Jielin ; Tepper, Pieter G. ; Strauss, Erick ; Poelarends, Gerrit J.
    Access to vitamin B5 [(R)-pantothenic acid] and both diastereoisomers of α-methyl-substituted vitamin B5 [(R)- and (S)-3-((R)-2,4-dihydroxy-3,3-dimethylbutanamido)-2-methylpropanoic acid] was achieved using a modular three-step biocatalytic cascade involving 3-methylaspartate ammonia lyase (MAL), aspartate-α-decarboxylase (ADC), β-methylaspartate-α-decarboxylase (CrpG) or glutamate decarboxylase (GAD), and pantothenate synthetase (PS) enzymes. Starting from simple non-chiral dicarboxylic acids (either fumaric acid or mesaconic acid), vitamin B5 and both diastereoisomers of α-methyl-substituted vitamin B5, which are valuable precursors for promising antimicrobials against Plasmodium falciparum and multidrug-resistant Staphylococcus aureus, can be generated in good yields (up to 70 %) and excellent enantiopurity ( > 99 % ee). This newly developed cascade process may be tailored and used for the biocatalytic production of various vitamin B5 derivatives by modifying the pantoyl or β-alanine moiety.
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    Recent Applications of Carbon-Nitrogen Lyases in Asymmetric Synthesis of Noncanonical Amino Acids and Heterocyclic Compounds
    ( 2020-10-01) Zhang, Jielin ; Abidin, Mohammad Z. ; Saravanan, Thangavelu ; Poelarends, Gerrit J.
    Carbon-nitrogen (C−N) lyases are enzymes that normally catalyze the cleavage of C−N bonds. Reversing this reaction towards carbon-nitrogen bond formation can be a powerful approach to prepare valuable compounds that could find applications in everyday life. This review focuses on recent (last five years) applications of native and engineered C−N lyases, either as stand-alone biocatalysts or as part of multienzymatic and chemoenzymatic cascades, in enantioselective synthesis of noncanonical amino acids and dinitrogen-fused heterocycles, which are useful tools for neurobiological research and important synthetic precursors to pharmaceuticals and food additives.
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    The broad amine scope of pantothenate synthetase enables the synthesis of pharmaceutically relevant amides
    ( 2021-05-28) Abidin, Mohammad Z. ; Saravanan, Thangavelu ; Strauss, Erick ; Poelarends, Gerrit J.
    Pantothenate synthetase from Escherichia coli (PSE. coli) catalyzes the ATP-dependent condensation of (R)-pantoic acid and β-alanine to yield (R)-pantothenic acid (vitamin B5), the biosynthetic precursor to coenzyme A. Herein we show that besides the natural amine substrate β-alanine, the enzyme accepts a wide range of structurally diverse amines including 3-amino-2-fluoropropionic acid, 4-amino-2-hydroxybutyric acid, 4-amino-3-hydroxybutyric acid, and tryptamine for coupling to the native carboxylic acid substrate (R)-pantoic acid to give amide products with up to > 99% conversion. The broad amine scope of PSE. coli enabled the efficient synthesis of pharmaceutically-relevant vitamin B5 antimetabolites with excellent isolated yield (up to 89%). This biocatalytic amide synthesis strategy may prove to be useful in the quest for new antimicrobials that target coenzyme A biosynthesis and utilisation.