Enantiomeric and diastereomeric high-performance liquid chromatographic separation of cyclic β-substituted α-amino acids on a copper(II)-d-penicillamine chiral stationary phase

Abstract

High-performance liquid chromatographic (HPLC) separation of stereoisomeric cyclic beta-substituted alpha-quaternary alpha-amino acids was performed by ligand-exchange on a copper(II)-D-penicillamine chiral stationary phase. The investigated amino acids are the 1-amino-2-methylcyclohexanecarboxylic acids, the 1-amino-2-hydroxycyclohexanecarboxylic acids, the 1-amino-2-methylcyclopentanecarboxylic acids and the trans-configured 1,2-diaminocyclohexanecarboxylic acids. The effects of the mobile phase composition (copper(II) concentration, type and content of organic modifier, pH) and the temperature on the enantio- and diastereoselectivity were studied and the conditions were optimised to resolve the four stereoisomers of each of the said amino acids in single chromatographic runs. A reversal of the elution order occurred for enantiomers of some of the amino acids in dependence on the acetonitrile content of the eluent. This phenomenon is explained by at least two different copper(II) complexes of the tridentate ligand penicillamine.

Dynamic ligand‐exchange chiral stationary phase from S‐benzyl‐(R)‐cysteine

“…R-SBC hydrophobically binds to the RP-18 solid support, thus producing a stable, dynamically coated chiral stationary phase. The presence of a sulfur atom in the amino acid side chain of the selector covalently 19 or hydrophobically bound 5,20,21 to the solid support has been already reported. The chiral selector in the coated phase was N,Sdioctyl-D-penicillamine, which binds to the C-18 carbon chains through both the C-8 alkyl substituents.…”

Enantioresolution of dl‐penicillamine

“…Chiral ligand exchange stationary phase prepared by embedding Cu (II)-N,S-dioctyl-D-penicillamine in a reversed-phase C 18 silica gel as reported by Oi et al (1995) was employed for resolution of enantiomers and diastereomers of cyclic b-substituted a-quaternary a-amino acids (Schlauch et al, 2000). The developed method proved to be successful for resolution of all the stereoisomers under study except for the two diastereomers of 1-amino-2-methylcyclopentanecarboxylic acid.…”

High‐performance liquid chromatographic enantioseparation of unusual secondary amino acids on a D‐penicillamine‐based chiral ligand exchange column

“…Several chiral ligand-exchange stationary phases have been applied so far with different chiral selectors, e.g., proline, 5,7 leucinol derivative, 13 norephedrine, 8 and penicillamine. 9,11 Applying copper(II) as the metal ion, the formation of a five-member chelate ring is normally expected and a square planar structure is usually proposed for the ternary complexes involving Cu(II) and chelating ligands. 7,8,12 Penicillamine theoretically may interact via its N-, O-, and S-atom acting as a tridentate ligand.…”

“…Zheng et al 14 used penicillamine as chiral ligand for ligand-exchange micellar electrokinetic chromatography and suggested that the pencillamine acts as a bidentate chelate, coordinating with Cu(II) via the amino nitrogen and the carboxyl oxygen (the -SH group does not participate in the chiral recognition process). Schlauch et al 11 proposed that penicillamine forms a bidentate complex via its N-, O-, or S-atoms and found that the acetonitrile content in the mobile phase has a crucial role in the discrimination of b-substituted a-amino acids.…”