REVERSED PHASE CHROMATOGRAPHIC RESOLUTION OF AMINO-ACID ENANTIOMERS WITH METAL-ASPARTAME ELUANTS

The resolution of amino acid enantiomers is of importance in peptide synthesis and structure determinations. While such methods as selective crystallization and enzyme degradation have been used, they are of limited use, frequently owing to their specificity. Chromatographic methods of analysis offer the possible advantage of resolving not only a pair of enantiomers but also a mixture of several amino acid enantiomers. Gas chromatographic separation of D-and L-amino acids has been described by, among others, Gil-Av, Feibush, and Bayer, who have used chiral stationary phases. The method, however, requires the derivatization of the amino acids to more volatile compounds suitable for GC separations. For this reason, modern high performance liquid chromatography (HPLC) can be a more attractive tool for enantiomeric resolutions. Several approaches have been advanced. Davankov and his co-workers and Lefebvre et al., to name a few, have used ligand exchange chromatography. There the separation of the enantiomers was achieved with an α-amino acid-copper(II) complex grafted onto a resin. Frequently the grafted amino acid of choice is proline, although, as Angelici has shown, other amino acids can form stereoselective complexes. Cram and his group have used chiral crown ethers bonded to chromatographic support for the separation of the optical isomers. A similar approach was reported by Blasius. More recently, Hara has reported the separation of the enantiomers o;f N-protected amino acid esters on L-valyl derivatives bonded to silica gel. Pirkle has demonstrated the resolution of 3, 5-dinitrobenzoyl derivatives of amino acids on chiral fluoro alcohols. Gaal and Inczedy as well as Yoneda and Yoshizawa have utilized optically active Co(III) compounds to achieve optical resolution. In an entirely different approach, Karger and his group have used the zinc(II) complex of L-2-alkyl-4-octyldiethylenetriamine in an aqueous mobile phase to obtain the resolution of the densyl derivatives of amino acids. Hare and Gil-Av have reported very recently the use of a proline-copper(ll) complex in an aqueous mobile phase as the resolving reagent in the ion-exchange separation of D-and L-amino acids. © 1979, American Chemical Society. All rights reserved.