High-performance Liquid Chromatographic Enantioseparation Research Articles

High performance liquid chromatography enantioseparation of chiral pharmaceuticals using tris(chloro-methylphenylcarbamate)s of cellulose

Chiral recognition abilities of a recently developed new type of cellulose phenylcarbamates were studied. These chiral stationary phases (CSPs) simultaneously contain both electron-withdrawing (Cl) and electron-donating (CH 3) substituents on the phenyl moiety. Chiral pharmaceuticals which belong to the various pharmacological groups (sedatives, hypnotics, anticonvulsants, Ca 2+ channel blockers, β-blockers, antitusives, antihystaminics, choleretics, diuretics, antimycotics, etc) were resolved to enantiomers. These new CSPs sometimes exhibit alternative chiral recognition ability to that most successful commercially available cellulosic CSP Chiralcel-OD and can be used as a good complement to it in analytical and preparative scale enantioseparations.

Diphenylethanediamine derivatives as chiral selectors V 1. Efficient normal-phase high-performance liquid chromatographic enantioseparation of underivatized chiral arylalcohols on four differently linked 3,5-dinitrobenzoyldiphenylethanediamine-derived chiral stationary phases

Four brush-type chiral stationary phases (CSPs) have been prepared, via immobilization of ( R, R)-3,5-dinitrobenzoyl-1,2-diphenylethane-1,2-diamine (DNB-DPEDA) with structurally different anchoring groups. These phases separate at normal-phase HPLC conditions the enantiomers of numerous underivatized chiral aromatic alcohols, including ArCH(OH)R, ArCH 2CH(OH)R, Ar(CH) 2CH(OH)R, simple tertiary arylalkylcarbinols and trans-2-arylcyclohexanols. In mobile phases of low polarity separations are characterized by considerate levels of enantioselectivity ( α = 1.1–2.7), excellent band shapes and short elution times. The hydroxyl group of the analytes is shown to be essential for stereodiscrimination, while π-basicity and steric bulkiness determine the magnitude of enantioselectivity. For simple structured arylalkylcarbinols a correlation is found between elution order and absolute configuration of the analyte. A rationale for molecular recognition of carbinol type analytes on DNB-DPEDA-derived CSPs is advanced. Their general applicability is demonstrated for a number of chiral auxiliaries, solvating agents and drug intermediates of carbinol structure.

High-performance liquid chromatographic enantioseparation of glycyl di- and tripeptides on native cyclodextrin bonded phases: Mechanistic considerations

Di- and tripeptides containing at least one glycine moiety were separated into enantiomers on χ-, β- and γ-cyclodextrin bonded phases after their precolumn derivatization with 9-fluorenylmethyl chloroformate (FMOC-Cl). It is shown that the choice of a suitable cyclodextrin bonded phase used with a nonaqueous polar mobile phase offers a wide range of possibilities to optimize enantioselectivity. Use of the FMOC derivative greatly enhances sensitivity, stability and enantioselectivity.It is postulated that under reversed-phase conditions the inclusion complex formation between the hydrophobic aromatic part of the FMOC-functionalized peptides and non-polar cyclodextrin cavity interior is the major factor contributing to retention. However, under these conditions there seems to be insufficient interaction between the hydrophilic peptide chain and cyclodextrin hydroxyls. Hence no chiral recognition and enantiomeric separation is observed. In systems operating with polar organic mobile phases the inclusion complex is suppressed as the cyclodextrin cavity is largely occupied by the mobile phase. The enantioselectivity observed is caused by hydrogen bonding between peptide chain and the hydroxyl groups at the mouth of the cyclodextrin. The stereospecific interactions depend very strongly on the cyclodextrin size, the length of the peptide chain and the mobile phase composition.

High-performance liquid chromatographic enantioseparation of intermediates relating to the total synthesis of (−)-physostigmine

()-Physostigmine (1) is a clinically useful anticholinesterase agent which has been used in the treatment of myasthenia gravis and glaucoma. More recently, selected ()-physostigmine analogues have also shown promise as Alzheimer’s disease therapeutic agents. Our interests in new (-)-physostigmine analogues have led us to develop a stereoselective synthesis of ()-physostigmine [I] (Fig. 1). To facilitate our synthetic effort and to ensure a high optical purity of the synthetic material, we required analytical high-performance liquid chromatographic (HPLC) enantioseparation of the intermediates as shown in the scheme. We report herein the application of derivatized cellulose-based chiral stationary phase (CSP) to the separation of these intermediates.

Direct high-performance liquid chromatographic resolution of dihydropyridine enantiomers

A direct high-performance liquid chromatographic enantioseparation on a chiral stationary phase using a protein as chiral selector was achieved for some dihydropyridines with different structural groups (amine, amide, acid and hydroxyl groups). The protein involved was α 1-acid glycoprotein and the work was mainly carried out with an EnantioPac column. An improved version of this chiral column (Chiral-AGP) was compared with the previous one and gave interesting results.