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

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)3453-3458
Number of pages6
JournalChemCatChem
Volume10
Issue number16
DOIs
Publication statusPublished - 21 Aug 2018

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

Keywords

  • Amino acids
  • Asymmetric catalysis
  • Enzyme catalysis
  • Quaternary stereogenic centers
  • Threonine aldolases

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

Fields of Expertise

  • Human- & Biotechnology

Cite this

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, Vol. 10, No. 16, 21.08.2018, p. 3453-3458.

Research output: Contribution to journalArticleResearchpeer-review

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