Chemoenzymatic Synthesis of ortho-, meta-, and para-Substituted Derivatives of L-threo-3-Benzyloxyaspartate, An Important Glutamate Transporter Blocker

Jandre de Villiers, Marianne de Villiers, Edzard M. Geertsema, Hans Raj, Gerrit J. Poelarends*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Scopus)
107 Downloads (Pure)

Abstract

A simple, three-step chemoenzymatic synthesis of L-threo-3-benzyloxyaspartate (L-TBOA), as well as L-TBOA derivatives with F, CF3, and CH3 substituents at the aromatic ring, starting from dimethyl acetylenedicarboxylate was investigated. These chiral amino acids, which are extremely difficult to prepare by chemical synthesis, form an important class of inhibitors of excitatory amino acid transporters involved in the regulation of glutamatergic neurotransmission. In addition, a new chemical procedure for the synthesis of racemic mixtures of TBOA and its derivatives was explored. These chemically prepared racemates are valuable reference compounds in chiral-phase HPLC to establish the enantiopurities of the corresponding chemoenzymatically prepared amino acids.

Original languageEnglish
Pages (from-to)1931-1934
Number of pages4
JournalChemCatChem
Volume7
Issue number13
DOIs
Publication statusPublished - 3-Jul-2015

Keywords

  • biocatalysis
  • excitatory amino acid transporters
  • glutamate
  • inhibitors
  • threo-3-benzyloxyaspartate
  • METHYLASPARTATE AMMONIA-LYASE
  • AMINO-ACID TRANSPORTERS
  • BETA-HYDROXYASPARTATE DERIVATIVES
  • 3-SUBSTITUTED ASPARTIC ACIDS
  • FUMARIC ACIDS
  • BENZYLOXYASPARTATE
  • SPECIFICITY
  • MECHANISM
  • SUBSTRATE
  • EAAT3

Cite this