Application of Threonine Aldolases for the Asymmetric Synthesis of α-Quaternary α-Amino Acids

Julia Blesl, Melanie Trobe, Felix Anderl, Rolf Breinbauer, Gernot A. Strohmeier, Kateryna Fesko

Publikation: Beitrag in einer FachzeitschriftArtikelForschungBegutachtung

Abstract

We report the synthesis of diverse β-hydroxy-α,α-dialkyl-α-amino acids with perfect stereoselectivity for the α-quaternary center through the action of l- and d-specific threonine aldolases. A wide variety of aliphatic and aromatic aldehydes were accepted by the enzymes and conversions up to >80 % were obtained. In the case of d-selective threonine aldolase from Pseudomonas sp., generally higher diastereoselectivities were observed. The applicability of the protocol was demonstrated by performing enzymatic reactions on preparative scale. Using the d-threonine aldolase from Pseudomonas sp., (2R,3S)-2-amino-3-(2-fluorophenyl)-3-hydroxy-2-methylpropanoic acid was generated in preparative amounts in one step with a diastereomeric ratio >100 favoring the syn-product. A Birch-type reduction enabled the reductive removal of the β-hydroxy group from (2S)-2-amino-3-hydroxy-2-methyl-3-phenylpropanoic acid to generate enantiopure l-α-methyl-phenylalanine via a two-step chemo-enzymatic transformation.

Originalspracheenglisch
Seiten (von - bis)3453-3458
Seitenumfang6
FachzeitschriftChemCatChem
Jahrgang10
Ausgabenummer16
DOIs
PublikationsstatusVeröffentlicht - 21 Aug 2018

Fingerprint

aldolase
Glycine Hydroxymethyltransferase
amino acids
Amino acids
pseudomonas
Amino Acids
Stereoselectivity
Acids
synthesis
Aldehydes
acids
phenylalanine
Enzymes
aldehydes
enzymes
products

Schlagwörter

    ASJC Scopus subject areas

    • !!Catalysis
    • Organische Chemie

    Fields of Expertise

    • Human- & Biotechnology

    Dies zitieren

    Application of Threonine Aldolases for the Asymmetric Synthesis of α-Quaternary α-Amino Acids. / Blesl, Julia; Trobe, Melanie; Anderl, Felix; Breinbauer, Rolf; Strohmeier, Gernot A.; Fesko, Kateryna.

    in: ChemCatChem, Jahrgang 10, Nr. 16, 21.08.2018, S. 3453-3458.

    Publikation: Beitrag in einer FachzeitschriftArtikelForschungBegutachtung

    @article{ef6771e44e724e66be9e124f8dac7d85,
    title = "Application of Threonine Aldolases for the Asymmetric Synthesis of α-Quaternary α-Amino Acids",
    abstract = "We report the synthesis of diverse β-hydroxy-α,α-dialkyl-α-amino acids with perfect stereoselectivity for the α-quaternary center through the action of l- and d-specific threonine aldolases. A wide variety of aliphatic and aromatic aldehydes were accepted by the enzymes and conversions up to >80 {\%} were obtained. In the case of d-selective threonine aldolase from Pseudomonas sp., generally higher diastereoselectivities were observed. The applicability of the protocol was demonstrated by performing enzymatic reactions on preparative scale. Using the d-threonine aldolase from Pseudomonas sp., (2R,3S)-2-amino-3-(2-fluorophenyl)-3-hydroxy-2-methylpropanoic acid was generated in preparative amounts in one step with a diastereomeric ratio >100 favoring the syn-product. A Birch-type reduction enabled the reductive removal of the β-hydroxy group from (2S)-2-amino-3-hydroxy-2-methyl-3-phenylpropanoic acid to generate enantiopure l-α-methyl-phenylalanine via a two-step chemo-enzymatic transformation.",
    keywords = "Amino acids, Asymmetric catalysis, Enzyme catalysis, Quaternary stereogenic centers, Threonine aldolases",
    author = "Julia Blesl and Melanie Trobe and Felix Anderl and Rolf Breinbauer and Strohmeier, {Gernot A.} and Kateryna Fesko",
    year = "2018",
    month = "8",
    day = "21",
    doi = "10.1002/cctc.201800611",
    language = "English",
    volume = "10",
    pages = "3453--3458",
    journal = "ChemCatChem",
    issn = "1867-3880",
    publisher = "Wiley-VCH",
    number = "16",

    }

    TY - JOUR

    T1 - Application of Threonine Aldolases for the Asymmetric Synthesis of α-Quaternary α-Amino Acids

    AU - Blesl, Julia

    AU - Trobe, Melanie

    AU - Anderl, Felix

    AU - Breinbauer, Rolf

    AU - Strohmeier, Gernot A.

    AU - Fesko, Kateryna

    PY - 2018/8/21

    Y1 - 2018/8/21

    N2 - We report the synthesis of diverse β-hydroxy-α,α-dialkyl-α-amino acids with perfect stereoselectivity for the α-quaternary center through the action of l- and d-specific threonine aldolases. A wide variety of aliphatic and aromatic aldehydes were accepted by the enzymes and conversions up to >80 % were obtained. In the case of d-selective threonine aldolase from Pseudomonas sp., generally higher diastereoselectivities were observed. The applicability of the protocol was demonstrated by performing enzymatic reactions on preparative scale. Using the d-threonine aldolase from Pseudomonas sp., (2R,3S)-2-amino-3-(2-fluorophenyl)-3-hydroxy-2-methylpropanoic acid was generated in preparative amounts in one step with a diastereomeric ratio >100 favoring the syn-product. A Birch-type reduction enabled the reductive removal of the β-hydroxy group from (2S)-2-amino-3-hydroxy-2-methyl-3-phenylpropanoic acid to generate enantiopure l-α-methyl-phenylalanine via a two-step chemo-enzymatic transformation.

    AB - We report the synthesis of diverse β-hydroxy-α,α-dialkyl-α-amino acids with perfect stereoselectivity for the α-quaternary center through the action of l- and d-specific threonine aldolases. A wide variety of aliphatic and aromatic aldehydes were accepted by the enzymes and conversions up to >80 % were obtained. In the case of d-selective threonine aldolase from Pseudomonas sp., generally higher diastereoselectivities were observed. The applicability of the protocol was demonstrated by performing enzymatic reactions on preparative scale. Using the d-threonine aldolase from Pseudomonas sp., (2R,3S)-2-amino-3-(2-fluorophenyl)-3-hydroxy-2-methylpropanoic acid was generated in preparative amounts in one step with a diastereomeric ratio >100 favoring the syn-product. A Birch-type reduction enabled the reductive removal of the β-hydroxy group from (2S)-2-amino-3-hydroxy-2-methyl-3-phenylpropanoic acid to generate enantiopure l-α-methyl-phenylalanine via a two-step chemo-enzymatic transformation.

    KW - Amino acids

    KW - Asymmetric catalysis

    KW - Enzyme catalysis

    KW - Quaternary stereogenic centers

    KW - Threonine aldolases

    UR - http://www.scopus.com/inward/record.url?scp=85050348166&partnerID=8YFLogxK

    U2 - 10.1002/cctc.201800611

    DO - 10.1002/cctc.201800611

    M3 - Article

    VL - 10

    SP - 3453

    EP - 3458

    JO - ChemCatChem

    JF - ChemCatChem

    SN - 1867-3880

    IS - 16

    ER -