Cinchona alkaloids as chiral selectores in liquid chromatography. Study of the enantioseparation conditions for α-amino acids.

R. ECHEVARRÍA, J. M. PADRÓ, C. B. CASTELLS Y S. KEUNCHKARIAN

San Francisco

Congreso; 44th International Symposium on High Performance Liquid Phase Separations and Related Techniques; 2016

Most natural compounds are formed by optically active constituent units that provide stereochemical specificity to biochemical processes. In particular, enantiomers of amino acids are involved in many of them [1], and then the development of strategies for enantiomeric resolution is a challenging task in the field of analytical separations.Cinchona alkaloids are well known natural products with therapeutic efficacy especially against malaria. In liquid chromatography, chiral stationary phases based on quinine and quinidine carbamates [2], as well as cinchonidine and quinine underivatized [3] covalently bounded to a solid support were employed for resolution of racemic amino acids when were used as ion-exchangers. And more recently, quinine and quinidine were successfully used as chiral mobile phase additives for chiral ligand-exchange chromatography (CLEC) forming ternary chelates constituted by Cu(II), quinine or quinidine and the D- or L-form of α-amino acids [4].The aim of this work was to systematically study the chromatographic variables that affect retention and enantioselectivity of α-amino acids under the CLEC mode using a conventional non-chiral column (C18). The following mobile phase parameters were evaluated: pH (8-9), organic solvent content (10-20%), type of transition cation Cu(II), Co(II), Zn(II) and Ni(II), and also column temperature (10-35°C).Finally an extended semiempirical model, PM6-DH+ allowed calculating formation energies and propose the geometry of the mixed diastereomers chelates formed between the α-amino acid pure enantiomer / the chiral selector / the divalent metallic cation.