Rapid chemoenzymatic route to glutamate transporter inhibitor l-TFB-TBOA and related amino acids

Haigen Fu, Sabry H H Younes, Mohammad Saifuddin, Pieter G Tepper, Jielin Zhang, Erik Keller, André Heeres, Wiktor Szymanski, Gerrit J Poelarends

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.

Original languageEnglish
Pages (from-to)2341-2344
JournalOrganic & biomolecular chemistry
Volume15
Issue number11
DOIs
StatePublished - 21 Mar 2017

Fingerprint

Amino Acid Transport Systems
Amino Acid Transport System X-AG
Excitatory Amino Acids
Amino Acids
Animal Behavior
Glutamate Receptors
Aspartic Acid
Synaptic Transmission
Economics
Inhibition (Psychology)

Keywords

  • neurotransmission
  • amino acids

Cite this

Fu, H., Younes, S. H. H., Saifuddin, M., Tepper, P. G., Zhang, J., Keller, E., ... Poelarends, G. J. (2017). Rapid chemoenzymatic route to glutamate transporter inhibitor l-TFB-TBOA and related amino acids. Organic & biomolecular chemistry, 15(11), 2341-2344. DOI: 10.1039/c7ob00305f

Fu, Haigen; Younes, Sabry H H; Saifuddin, Mohammad; Tepper, Pieter G; Zhang, Jielin; Keller, Erik; Heeres, André; Szymanski, Wiktor; Poelarends, Gerrit J / Rapid chemoenzymatic route to glutamate transporter inhibitor l-TFB-TBOA and related amino acids.

In: Organic & biomolecular chemistry, Vol. 15, No. 11, 21.03.2017, p. 2341-2344.

Research output: Scientific - peer-reviewArticle

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author = "Haigen Fu and Younes, {Sabry H H} and Mohammad Saifuddin and Tepper, {Pieter G} and Jielin Zhang and Erik Keller and André Heeres and Wiktor Szymanski and Poelarends, {Gerrit J}",
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Fu, H, Younes, SHH, Saifuddin, M, Tepper, PG, Zhang, J, Keller, E, Heeres, A, Szymanski, W & Poelarends, GJ 2017, 'Rapid chemoenzymatic route to glutamate transporter inhibitor l-TFB-TBOA and related amino acids' Organic & biomolecular chemistry, vol 15, no. 11, pp. 2341-2344. DOI: 10.1039/c7ob00305f

Rapid chemoenzymatic route to glutamate transporter inhibitor l-TFB-TBOA and related amino acids. / Fu, Haigen; Younes, Sabry H H; Saifuddin, Mohammad; Tepper, Pieter G; Zhang, Jielin; Keller, Erik; Heeres, André; Szymanski, Wiktor; Poelarends, Gerrit J.

In: Organic & biomolecular chemistry, Vol. 15, No. 11, 21.03.2017, p. 2341-2344.

Research output: Scientific - peer-reviewArticle

TY - JOUR

T1 - Rapid chemoenzymatic route to glutamate transporter inhibitor l-TFB-TBOA and related amino acids

AU - Fu,Haigen

AU - Younes,Sabry H H

AU - Saifuddin,Mohammad

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AU - Zhang,Jielin

AU - Keller,Erik

AU - Heeres,André

AU - Szymanski,Wiktor

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N2 - 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.

AB - 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.

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Fu H, Younes SHH, Saifuddin M, Tepper PG, Zhang J, Keller E et al. Rapid chemoenzymatic route to glutamate transporter inhibitor l-TFB-TBOA and related amino acids. Organic & biomolecular chemistry. 2017 Mar 21;15(11):2341-2344. Available from, DOI: 10.1039/c7ob00305f