HPLC enantioseparation of β²‐homoamino acids using crown ether‐based chiral stationary phase

Abstract

RP high-performance liquid chromatographic methods were developed for the enantioseparation of eleven unusual beta(2)-homoamino acids. The underivatized analytes were separated on a chiral stationary phase containing (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid as chiral selector. The effects of organic (alcoholic) and acidic modifiers, the mobile phase composition and temperature on the separation were investigated. The structures of the substituents in the alpha-position of the analytes substantially influenced the retention and resolution. The elution sequence was determined in some cases: the S enantiomers eluted before the R enantiomers.

Enantioresolution of Amino Acids: A Decade’s Perspective, Prospects and Challenges

“…The chromatographic retention and resolution behavior were found to depend on the structure of the substituents in β-position and ionic strength of the mobile phase [104]. Péter and co-workers [106] separated β 2 -AAs bearing aliphatic and aromatic side-chains on a CSP of (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid attached to silica with a short, 3-methylene-unit spacer: all aromatic β 2 -AAs enantiomers were baselineresolved, while AAs with alkyl side-chains showed partial separation. Lee et al [107] used two different CSPs based on 3 methylene-unit or 11 methylene-unit spacer group in (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid and the two were compared for the enantiomeric separation of γ-AAs; longer spacer unit provided higher resolution.…”

Recent advances in the direct and indirect liquid chromatographic enantioseparation of amino acids and related compounds: A review

“…The underivatized analytes of 11 alkyl-and aryl-substituted unusual ␤ 2 -homoamino acids were separated on end-capped CSP containing (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid as chiral selector [60]. The effects of organic (MeOH, EtOH, PrOH, IPA) and acidic modifiers (AcOH, TFA, HClO 4 , H 2 SO 4 , H 3 PO 4 ), the mobile phase composition and temperature on the separation were investigated.…”

Development of HPLC Chiral Stationary Phases Based on (+)‐(18‐Crown‐6)‐2,3,11,12‐tetracarboxylic Acid and Their Applications

“…), were resolved. CSP 1 was quite successful in the resolution of both β‐3‐homo‐amino acids and β‐2‐homo‐amino acids . Methanol in water containing a small amount of acetic or sulfuric acid was used as a mobile phase for the resolution of β‐amino acids on CSP 1 .…”

“…Methanol in water containing a small amount of acetic or sulfuric acid was used as a mobile phase for the resolution of β‐amino acids on CSP 1 . Acetic acid was usually used as an acidic modifier for the resolution of β‐3‐homo‐amino acids on CSP 1 , but sulfuric acid was also found to be useful as an acidic modifier for the resolution of some β‐2‐homo‐amino acids . Enantiomeric and diasteromeric pairs of cyclic β‐amino acids such as isoxazoline‐fused 2‐aminocyclopentanecarboxylic acids were also resolved quite well on CSP 1 …”