Resolution of the Optical Isomers of Underivatisized Amino Acids on Chemically Bonded Chiral Phases by Ligand Exchange Chromatography

Jellenz, W.; Santi, W.

doi:10.1080/01483918108059966

Cited by 73 publications

(21 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Chiral ligand exchange HPLC was performed on a column (4.6 × 120 mm) containing (S)-pipecolic acid chemically bound to a silica-based packing material following a procedure used for attachment of (S)-proline. 20 The column was thermostated at 50°C and eluted at 1 ml/min with an aqueous solution of KH 2 PO 4 (50 mM; pH 4.6) containing 0.1 mM CuSO 4 . The HPLC instrument used for the analyses consisted of a Waters M510 pump, a Waters U6K injector, and a Waters M991 Photodiode Array Detector with a detection wavelength of 225 nm.…”

Section: Chiral Liquid Chromatographymentioning

confidence: 99%

Resolution, configurational assignment, and enantiopharmacology of 2-amino-3-[3-hydroxy-5-(2-methyl-2H-tetrazol-5-yl)isoxazol-4-yl]propionic acid, a potent GluR3- and GluR4-preferring AMPA receptor agonist

Vogensen¹,

Jensen

Stensbøl³

et al. 2000

Chirality

View full text Add to dashboard Cite

We have previously shown that (RS)-2-amino-3-[3-hydroxy-5-(2-methyl-2H-tetrazol-5-yl)isoxazol -4-yl] propionic acid (2-Me-Tet-AMPA) is a selective agonist at (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptors, markedly more potent than AMPA itself, whereas the isomeric compound 1-Me-Tet-AMPA is essentially inactive. We here report the enantiopharmacology of 2-Me-Tet-AMPA in radioligand binding and cortical wedge electrophysiological assay systems, and using cloned AMPA (GluR1-4) and kainic acid (KA) (GluR5, 6, and KA2) receptor subtypes expressed in Xenopus oocytes. 2-Me-Tet-AMPA was resolved using preparative chiral HPLC. Zwitterion (-)-2-Me-Tet-AMPA was assigned the (R)-configuration based on an X-ray crystallographic analysis supported by the elution order of (-)- and (+)-2-Me-Tet-AMPA using four different chiral HPLC columns and by circular dichroism spectra. None of the compounds tested showed detectable affinity for N-methyl-D-aspartic acid (NMDA) receptor sites, and (R)-2-Me-Tet-AMPA was essentially inactive in all of the test systems used. Whereas (S)-2-Me-Tet-AMPA showed low affinity (IC(50) = 11 microM) in the [(3)H]KA binding assay, it was significantly more potent (IC(50) = 0.009 microM) than AMPA (IC(50) = 0.039 microM) in the [(3)H]AMPA binding assay, and in agreement with these findings, (S)-2-Me-Tet-AMPA (EC(50) = 0.11 microM) was markedly more potent than AMPA (EC(50) = 3.5 microM) in the electrophysiological cortical wedge model. In contrast to AMPA, which showed comparable potencies (EC(50) = 1.3-3.5 microM) at receptors formed by the AMPA receptor subunits (GluR1-4) in Xenopus oocytes, more potent effects and a substantially higher degree of subunit selectivity were observed for (S)-2-Me-Tet-AMPA: GluR1o (EC(50) = 0.16 microM), GluR1o/GluR2i (EC(50) = 0.12 microM), GluR3o (EC(50) = 0.014 microM) and GluR4o (EC(50) = 0.009 microM). At the KA-preferring receptors GluR5 and GluR6/KA2, (S)-2-Me-Tet-AMPA showed much weaker agonist effects (EC(50) = 8.7 and 15.3 microM, respectively). It is concluded that (S)-2-Me-Tet-AMPA is a subunit-selective and highly potent AMPA receptor agonist and a potentially useful tool for studies of physiological AMPA receptor subtypes.

show abstract

Section: Chiral Liquid Chromatographymentioning

confidence: 99%

Resolution, configurational assignment, and enantiopharmacology of 2-amino-3-[3-hydroxy-5-(2-methyl-2H-tetrazol-5-yl)isoxazol-4-yl]propionic acid, a potent GluR3- and GluR4-preferring AMPA receptor agonist

Vogensen¹,

Jensen

Stensbøl³

et al. 2000

Chirality

View full text Add to dashboard Cite

show abstract

“…Chiral ligand exchange HPLC was performed on a column (4.6 × 120 mm) containing (S)-pipecolic acid chemically bound to a silica-based packing material following a procedure used for attachment of (S)-proline. 31 The column was connected to an HPLC instrumentation consisting of a Waters M510 pump, a Waters UK6 injector, and a Waters M991 Photodiode Array Detector with a detection wavelength of 254 nm. The column was thermostated at 50°C and eluted with an aqueous solution of KH 2 PO 4 (50 mM; pH 4.6) containing 20 µM CuSO 4 at 1.0 ml/min.…”

Section: Chiral Liquid Chromatographymentioning

confidence: 99%

AMPA receptor agonists: Resolution, configurational assignment, and pharmacology of (+)-(S)- and (-)-(R)-2-amino-3-[3-hydroxy-5-(2-pyridyl)-isoxazol-4-yl]-propionic acid (2-Py-AMPA)

Johansen¹,

Ebert²,

Falch³

et al. 1997

Chirality

View full text Add to dashboard Cite

“…The bonded support was loaded with Cu 2 § and racemic amino acids could be'resolved into enantiomers. 67 Other amino acids were incorporated in the CSP and compounds like enantiomers of hydroxy acids, amino acid derivatives and dipeptides could be separated. ~ Mobile phases were aqueous solvents containing Cu 2 § Besides amino acids, other compounds capable of forming ligand-exchange complexes have been incorporated in the CSP, such as tartaric acids.…”

Section: Ligand-exchange Phasesmentioning

confidence: 99%

Chromatographic separation of enantiomers

Feitsma

Drenth

1988

Pharmaceutisch Weekblad Scientific Edition

View full text Add to dashboard Cite

In this paper a review is presented on the chromatographic analysis of enantiomers with special attention to high pressure liquid chromatography. Also, some examples of resolution of racemates by thin layer chromatography and gas chromatography are given. The various procedures in the surveyed literature have been divided into three main classes: procedures with formation of diastereomeric compounds prior to the chromatographic separation, procedures in which a chiral mobile phase is used, and procedures with the use of a chiral stationary phase. These methods are subdivided and some examples of their application to drugs and related compounds are presented.

show abstract

Resolution of the Optical Isomers of Underivatisized Amino Acids on Chemically Bonded Chiral Phases by Ligand Exchange Chromatography

Cited by 73 publications

References 26 publications

Resolution, configurational assignment, and enantiopharmacology of 2-amino-3-[3-hydroxy-5-(2-methyl-2H-tetrazol-5-yl)isoxazol-4-yl]propionic acid, a potent GluR3- and GluR4-preferring AMPA receptor agonist

Resolution, configurational assignment, and enantiopharmacology of 2-amino-3-[3-hydroxy-5-(2-methyl-2H-tetrazol-5-yl)isoxazol-4-yl]propionic acid, a potent GluR3- and GluR4-preferring AMPA receptor agonist

AMPA receptor agonists: Resolution, configurational assignment, and pharmacology of (+)-(S)- and (-)-(R)-2-amino-3-[3-hydroxy-5-(2-pyridyl)-isoxazol-4-yl]-propionic acid (2-Py-AMPA)

Chromatographic separation of enantiomers

Contact Info

Product

Resources

About