2-Keto-3-Deoxy-l-Rhamnonate Aldolase (YfaU) as Catalyst in Aldol Additions of Pyruvate to Amino Aldehyde Derivatives

Karel Hernández, Ariadna Gómez, Jesús Joglar, Jordi Bujons, Teodor Parella, Pere Clapés

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    9 Citations (Scopus)

    Abstract

    © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 4-Hydroxy-2-keto acid derivatives are versatile building blocks for the synthesis of amino acids, hydroxy carboxylic acids and chiral aldehydes. Pyruvate aldolases are privileged catalysts for a straightforward access to this class of keto acid compounds. In this work, a Class II pyruvate aldolase from Escherichia coli K-12, 2-keto-3-deoxy-l-rhamnonate aldolase (YfaU), was evaluated for the synthesis of amino acid derivatives of proline, pipecolic acid, and pyrrolizidine-3-carboxylic acid. The aldol addition of pyruvate to N-protected amino aldehydes was the key enzymatic aldol addition step followed by catalytic intramolecular reductive amination. The corresponding N-Cbz-amino-4-hydroxy-2-keto acid (Cbz=benzyloxycarbonyl) precursors were obtained in 51–95% isolated yields and enantioselectivity ratios from 26:74 to 95:5, with chiral α-substituted N-Cbz-amino aldehydes. (S)-N-Cbz-amino aldehydes gave aldol adducts with preferentially (R)-configuration at the newly formed stereocenter, whereas the contrary is true for (R)-N-Cbz-amino aldehydes. Addition reactions to achiral amino aldehydes rendered racemic aldol adducts. Molecular models of the pre-reaction ternary complexes YfaU-pyruvate enolate-acceptor aldehyde were constructed to explain the observed stereochemical outcome of the reactions. Catalytic reductive amination of the aldol adducts yielded 4-hydroxy-2-pipecolic acid, and unprecedented C-5 substituted 4-hydroxyproline and pyrrolizidine-3-carboxylic acid derivatives. (Figure presented.).
    Original languageEnglish
    Pages (from-to)2090-2100
    JournalAdvanced Synthesis and Catalysis
    Volume359
    Issue number12
    DOIs
    Publication statusPublished - 19 Jun 2017

    Keywords

    • aldol reaction
    • amino acids
    • amino aldehydes
    • asymmetric catalysis
    • biocatalysis
    • biotransformations
    • pyruvate aldolases

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