title: Chemoenzymatic Synthesis ofortho-,meta-, andpara-Substituted Derivatives of l-threo-3-Benzyloxyaspartate, An Important Glutamate Transporter Blocker.
abstract: A simple, three-step chemoenzymatic synthesis of l-threo-3-benzyloxyaspartate (l-TBOA), as well as l-TBOA derivatives with F, CF3, and CH3substituents 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.
authors.affiliation: Department of Pharmaceutical Biology, Groningen Research Institute of Pharmacy University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen (The Netherlands ).
authors.forename: Jandré
authors.initials: J
authors.lastname: de Villiers
authors.affiliation: Department of Pharmaceutical Biology, Groningen Research Institute of Pharmacy University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen (The Netherlands ).
authors.forename: Marianne
authors.initials: M
authors.lastname: de Villiers
authors.affiliation: Department of Pharmaceutical Biology, Groningen Research Institute of Pharmacy University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen (The Netherlands ).
authors.forename: Edzard M
authors.initials: EM
authors.lastname: Geertsema
authors.affiliation: Department of Pharmaceutical Biology, Groningen Research Institute of Pharmacy University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen (The Netherlands ) ; Current address: Chr-Hansen A/S, Boge Alle 10-12 2970 Horsholm (Denmark).
authors.forename: Hans
authors.initials: H
authors.lastname: Raj
authors.affiliation: Department of Pharmaceutical Biology, Groningen Research Institute of Pharmacy University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen (The Netherlands ).
authors.forename: Gerrit J
authors.initials: GJ
authors.lastname: Poelarends
keywords: biocatalysis; excitatory amino acid transporters; glutamate; inhibitors; threo-3-benzyloxyaspartate