Resolution of neuroexcitatory non-protein amino acid enantiomers by high-performance liquid chromatography utilising pre-column derivatisation with o-phthaldialdehyde chiral thiols : Application to ω-N-oxalyl diamino acids
✍ Scribed by Melvin R. Euerby; Peter B. Nunn; Lynda Z. Partridge
- Book ID
- 104145799
- Publisher
- Elsevier Science
- Year
- 1989
- Tongue
- English
- Weight
- 462 KB
- Volume
- 466
- Category
- Article
- ISSN
- 1873-3778
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✦ Synopsis
The o-N-oxalyl derivatives of L-u$-diaminopropanoic acid (L+ODAP, la) and L-a,y-diaminobutanoic acid (L-y-ODAB, 2a) are both natural products which were first isolated from the seeds of Lathyrus specieslp3, L-fi-ODAP is believed to be the major causative agent of neurolathyrism, a crippling neurological diseaseL6. The compound is a powerful convulsant' and is neuroexcitatory to central nervous system neurones'-', acting at the quisqualate and kainate receptors'-"' [i.e. as distinct from N-methyl-D-aspartate (NMDA) receptors].
Pharmacological and biochemical interest in the longer chain L-w-N-oxalyl derivatives of diamino acids, together with the possibility that the corresponding D isomers might act as important antagonists'l, prompted us to synthesise the D-and L-o-N-oxalyl derivatives of diaminobutanoic acid (y-ODAB, 2a,b), ornithine (a-OORN, 3a,b) and lysine (E-OLYS, 4a,b) (see Fig. 1). The synthetic, pharmacological and biochemical properties of these compounds will be described elsewhere12*13. A knowledge of their optical purity was essential before a study of the pharmacological and biochemical activity could be undertaken, since L-/I-ODAP activates quisqualate and kainate receptors to differing degrees and in a concentration-dependent manner", whereas D-,%ODAP is a weak antagonist at the NMDA receptor14.
To date, optical purity has been ensured by the use of "optically pure" starting materials, optical rotation and rotary dispersion measurements. However, these methods are insensitive to contamination with small quantities of the minor enantiomer, either as a result of being induced by racemisation in the synthetic procedure, or being present in the "optically pure" starting materials.