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Rigid nonproteinogenic cyclic amino acids as ligands for glutamate receptors: trans ‐Tris(homoglutamic) acids
Author(s) -
Meyer Udo,
Bisel Philippe,
BräunerOsborne Hans,
Madsen Ulf,
Höfner Georg,
Wanner Klaus Th.,
Frahm August Wilhelm
Publication year - 2005
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.20110
Subject(s) - chemistry , diastereomer , strecker amino acid synthesis , amino acid , chirality (physics) , nitrile , hydrolysis , enantiomer , stereochemistry , chiral auxiliary , tris , hydrochloride , enantiomeric excess , organic chemistry , enantioselective synthesis , catalysis , biochemistry , nambu–jona lasinio model , chiral symmetry breaking , physics , quantum mechanics , quark
The second‐generation asymmetric synthesis of the trans ‐tris(homoglutamic) acids reported herein proceeds via Strecker reaction of chiral ketimines, obtained from condensation of racemic 2‐ethoxycarbonylmethylcyclopentanone and commercially available ( S )‐ and ( R )‐1‐phenylethylamine, respectively. In the key stereodifferentiating step, the cyanide addition leads to mixtures of diastereomeric α‐amino nitrile‐esters, the composition of which is independent of the reaction temperature and the type of the solvent, respectively. Hydrolysis of the α‐amino nitrile‐esters with concentrated H 2 SO 4 yielded diastereomeric mixtures of secondary α‐amino amido‐esters, which after separation were hydrogenolyzed and hydrolyzed each to the enantiomeric trans ‐1‐amino‐2‐carboxymethylcyclopentanecarboxylic acids. Their configuration was completely established by NMR methods, CD spectra, and X‐ray analysis of the trans ‐1 S ,2 R ‐configured secondary α‐amino amido‐ester. In receptor binding assays and functional tests, trans ‐1 S ,2 R ‐1‐amino‐2‐carboxymethylcyclopentanecarboxylic acid hydrochloride was found to behave as a selective mGluR 2 ‐antagonist without relevant binding properties at iGluRs. Chirality 17:99–107, 2005. © 2005 Wiley‐Liss, Inc.