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Chemoenzymatic Synthesis of ortho ‐, meta ‐, and para ‐Substituted Derivatives of L ‐ threo ‐3‐Benzyloxyaspartate, An Important Glutamate Transporter Blocker
Author(s) -
de Villiers Jandré,
de Villiers Marianne,
Geertsema Edzard M.,
Raj Hans,
Poelarends Gerrit J.
Publication year - 2015
Publication title -
chemcatchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.497
H-Index - 106
eISSN - 1867-3899
pISSN - 1867-3880
DOI - 10.1002/cctc.201500318
Subject(s) - chemistry , excitatory amino acid transporter , glutamatergic , amino acid , enantiomer , transporter , stereochemistry , combinatorial chemistry , glutamate receptor , biochemistry , receptor , gene
A simple, three‐step chemoenzymatic synthesis of L ‐ threo ‐3‐benzyloxyaspartate ( L ‐TBOA), as well as L ‐TBOA derivatives with F, CF 3 , and CH 3 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.