title: Rapid chemoenzymatic route to glutamate transporter inhibitor l-TFB-TBOA and related amino acids.
abstract: The complex amino acid (l-threo)-3-[3-[4-(trifluoromethyl)benzoylamino]benzyloxy]aspartate (l-TFB-TBOA) and its derivatives are privileged compounds for studying the roles of excitatory amino acid transporters (EAATs) in regulation of glutamatergic neurotransmission, animal behavior, and in the pathogenesis of neurological diseases. The wide-spread use of l-TFB-TBOA stems from its high potency of EAAT inhibition and the lack of off-target binding to glutamate receptors. However, one of the main challenges in the evaluation of l-TFB-TBOA and its derivatives is the laborious synthesis of these compounds in stereoisomerically pure form. Here, we report an efficient and step-economic chemoenzymatic route that gives access to enantio- and diastereopure l-TFB-TBOA and its derivatives at multigram scale.
authors.affiliation: Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands. g.j.poelarends@rug.nl.
authors.forename: Haigen
authors.initials: H
authors.lastname: Fu
authors.forename: Sabry H H
authors.initials: SH
authors.lastname: Younes
authors.forename: Mohammad
authors.initials: M
authors.lastname: Saifuddin
authors.forename: Pieter G
authors.initials: PG
authors.lastname: Tepper
authors.forename: Jielin
authors.initials: J
authors.lastname: Zhang
authors.forename: Erik
authors.initials: E
authors.lastname: Keller
authors.forename: André
authors.initials: A
authors.lastname: Heeres
authors.forename: Wiktor
authors.initials: W
authors.lastname: Szymanski
authors.forename: Gerrit J
authors.initials: GJ
authors.lastname: Poelarends
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000037:antagonists & inhibitors*; D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D004798:Enzymes / Q000378:metabolism*; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: C508240:(2S,3S)-3-(3-(4-(trifluoromethyl)benzoylamino)benzyloxy)aspartate; D027322:Amino Acid Transport System X-AG; D000596:Amino Acids; D004798:Enzymes; D001224:Aspartic Acid