Separation of the enantiomers of substituted dihydrofurocoumarins by HPLC using macrocyclic glycopeptide chiral stationary phases

Abstract

Enantiomer separations by HPLC using the macrocyclic glycopeptides teicoplanin (Chirobiotic T), teicoplanin aglycon (Chirobiotic TAG), and ristocetin A (Chirobiotic R) chiral stationary phases (CSP) have been achieved on a unique series of potentially biologically active racemic analogues of dihydrofurocoumarin. The macrocyclic glycopeptides have proven to be very selective for this class of compound. All of the 28 chiral analogues examined afforded baseline separation on at least one of the macrocyclic glycopeptide CSP. The teicoplanin CSP showed the broadest enantioselectivity with 24 of the compounds baseline separated. The TAG and the R CSP produced 23 and 14 baseline separations respectively. All three mobile phase modes, i.e. normal phase (NP), reversed phase (RP), and new polar organic modes (PO), have been evaluated. The NP mode proved to be most effective for the separation of chiral dihydrofurocoumarins on all CSP tested. In the reversed phase (RP) mode, all three CSP separated a similar number of compounds. It was observed that the structural characteristics of the analytes and steric effects are very important factors leading to chiral recognition. Hydrogen bonding was found to play a secondary role in chiral discrimination in the normal phase and polar organic modes. Hydrophobic interactions are important for chiral separation in the reversed-phase mode. Chromatographic retention data does not provide information on the absolute configuration of these chiral dihydrofurocoumarin derivatives. However, when coupled with circular dichroism using the exciton coupling chirality method, the enantiomer elution order and the absolute configuration of some chiral dihydrofurocoumarins were successfully determined.

Evaluation and comparison of a methylated teicoplanin aglycone to teicoplanin aglycone and natural teicoplanin chiral stationary phases

“…The effect of the carbohydrate moiety, i.e., T versus TAG, on retention and enantiomeric separation of some analytes has been discussed in previous papers [5,10]. It was shown that cleavage of the saccharides yields improved enantioresolution of most common amino acids and some other analytes for which the aglycone basket contains important sites for chiral recognition [5].…”

“…It was shown that cleavage of the saccharides yields improved enantioresolution of most common amino acids and some other analytes for which the aglycone basket contains important sites for chiral recognition [5]. Both these chiral selectors (i.e., the T and the TAG) offer similar possibilities for chiral resolution of racemic analogs of dihydrofurocoumarin [10]. However, greater retention and worse efficiency were observed on the TAG column.…”

New high-performance liquid chromatography method for the determination of (R)-warfarin and (S)-warfarin using chiral separation on a glycopeptide-based stationary phase

“…The native cyclodextrins have been described to be inefficient at separating furocoumarin enantiomers in the reversed-phase mode [14], and this finding was in agreement with our experiments. The macrocyclic glycopeptides have shown selectivity for coumarin-based compounds [15,16], but any study employing a vancomycin-based column for the separation of warfarin enantiomers in biological samples has not been reported yet. The thermodynamic study evaluated from an experimental point of view the effect of temperature changes with four macrocyclic glycopeptide chiral stationary phase has been described [17].…”

Evaluation of the Edman degradation product of vancomycin bonded to core‐shell particles as a new HPLC chiral stationary phase

“…Purified and bonded to silica particles, they make useful chiral stationary phases (CSPs) with a broad spectrum of interactions and therefore applicability . The macrocyclic glycopeptide‐based CSPs are multimodal, meaning they are stable and efficient in normal phase (NP), reversed phase (RP), polar organic mode (POM), and polar ionic mode (PIM) . The most distinctive feature of macrocyclic glycopeptides as chiral selectors is their ionic character.…”