Synthesis of a new kainic acid based selective ligand as a potential photoaffinity label of non-NMDA excitatory amino acid receptors in chicken brain

Acta Chem Scand (Cph). 1994 Jan;48(1):76-9. doi: 10.3891/acta.chem.scand.48-0076.

Abstract

The synthesis of two analogues of kainic acid (KA) incorporating photo-activatible moieties attached either on the gamma-carboxy function (gamma-amide 1) or the isopropenyl side-chain (amide 2) is described. The synthesis of the former amide involves coupling of N-(tert-butoxycarbonyl)-protected alpha-diphenylmethyl kainate with 2-(4-azidobenzamido)ethylamine (5) followed by trifluoroacetic acid mediated complete deprotection. Amide 2 was synthesized by palladium-mediated allylic amination, with 4,4'-dimethoxybenzhydrylamine (DMBA), of N-(9-fluorenylmethoxycarbonyl)-protected dimethyl kainate, followed by splitting the DMB-group with formic acid, coupling with N-hydroxysuccinimidoyl 4-azidobenzoate and finally complete deprotection by saponification. Preliminary pharmacological studies in chicken brain membranes showed that amide 2 is a stronger inhibitor of [3H]KA binding on chicken cerebellar membranes than is amide 1 and that amide 2 has specificity only for the cerebellar, as opposed to the telencephalon, type of non-NMDA binding sites.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Affinity Labels*
  • Animals
  • Azides / chemical synthesis*
  • Azides / metabolism
  • Brain / metabolism*
  • Cell Membrane / metabolism
  • Cerebellum / metabolism
  • Chickens
  • Kainic Acid / analogs & derivatives*
  • Kainic Acid / chemical synthesis
  • Kainic Acid / metabolism
  • Molecular Structure
  • Photochemistry
  • Receptors, Amino Acid / metabolism*
  • Telencephalon / metabolism

Substances

  • 4-(1-(4-azidobenzamidomethyl)ethenyl)-2-carboxypyrrolidin-3-ylacetic acid
  • Affinity Labels
  • Azides
  • Receptors, Amino Acid
  • Kainic Acid