Screening primary racemic amines for enantioseparation by derivatized polysaccharide and cyclofructan columns

Abstract

It is a challenge to separate the enantiomers of native chiral amines prone to deleterious silanol interactions. A set of 39 underivatized chiral primary amines was screened for enantiomeric separation. Seven recently introduced commercial chiral columns were tested. They included six polysaccharide based chiral stationary phases (CSP) with bonded derivatives, ChiralPak® IA, IB, IC, ID, IE and IF columns and a cyclofructan derivatized CSP, Larihc® CF6-P column. Both the normal phase (NP) mode with heptane/alcohol mobile phases and the polar organic (PO) mode with acetonitrile/alcohol were evaluated. It was found that the cyclofructan based CSP demonstrated the highest success rate in separating primary amines in the PO mode with only one chiral amine not resolved. It is shown that, when screening the columns, there is no standard optimal condition; an excellent mobile phase composition for one column may be poorly suited to another one. Although butylamine was a good mobile phase additive for the polysaccharide columns in both PO and NP modes, it was detrimental to the enantio-recognition capability of the cyclofructan column. Triethylamine was the appropriate silanol screening agent for this latter column.

Liquid Chromatographic Enantioseparations Utilizing Chiral Stationary Phases Based on Crown Ethers and Cyclofructans

“…In a screening study, the enantioseparation capability of Larihc CF6-P was evaluated and compared to six polysaccharide-based CSPs applying the NP mode with n -heptane/ethanol or PO mode with acetonitrile/methanol or 2-propanol eluent systems [ 51 ]. The CF-based CSP demonstrated the highest success rate in the separation of 39 nonderivatized chiral primary amines in PO mode.…”

Analytical Separation of Closantel Enantiomers by HPLC

“…Thus, the bulkiness of IPA could alter the size and shape of the helical grooves to become more favorable for The above results indicated that the branched alcohol (IPA) has a higher ability to modify the steric environment in chiral grooves of the amylose polymeric backbone, which likely seems to be correlated with the high steric size of IPA. Thus, the bulkiness of IPA could alter the size and shape of the helical grooves to become more favorable for enantioseparation [18]. Therefore, the reason for the enantioselectivity on Chiralpak AD−3 strongly relies on the modification of chiral grooves that lets portions of the closantel enantiomers enter and exhibit interactions with the active part of the polymer.…”

“…To date, few studies have investigated the chiral separation of closantel enantiomers using HPLC [ 14 ]. This research aimed to develop analytical separations of closantel enantiomers using the normal-phase (NP) HPLC mode with different types of chiral selectors such as tris carbamates of amylose polysaccharides [ 15 , 16 ], isopropyl carbamates of cyclofructans [ 17 , 18 , 19 ], and β-cyclodextrins derivatives [ 20 ]. Filling the gap in the analytical separation of racemic drugs has great significance for the chemical, pharmaceutical, and biological fields.…”

State-of-the-art and recent developments of immobilized polysaccharide-based chiral stationary phases for enantioseparations by high-performance liquid chromatography (2013–2017)

“…have also been determined, especially in commercial products or biological samples (pharmaceutical formulations, human urine, human or animal blood, human plasma, animal serum, etc.). Another heterogeneous group of analytes, including connectors for building metal-organic frameworks [116,117,124], intermediates for the synthesis of pharmaceuticals [111], natural and synthetic compounds [39,113,121,120], biological compounds [82,112,58,71,78,86,[61][62][63]77,75], natural alkaloids [121], biomolecules [115,54], organometallic compounds [119] and chiral metabolites [103,108,100,97,102,59,63,52] has been enantioseparated with these immobilized polysaccharides CSPs (see Table 2-4). Fig.…”