Enantioselective HPLC

The solvent used was hexane-isopropanol(4 1). Later, Allenmark and colleagues133 obtained enantioselective HPLC retention of a series of alkyl carboxymethyl sulphoxides (and other sulphoxides and classes) on a column of 3,5-... 

The solvent used was hexane-isopropanol(4 1). Later, Allenmark and colleagues obtained enantioselective HPLC retention of a series of alkyl carboxymethyl sulphoxides (and other sulphoxides and classes) on a column of (R)-lV-(3,5-dinitrobenzoyl)phenylglycine covalently bound via an amide bond (CSP 1), or ionically bound (CSP 2), to 3-aminopropylsilica the mobile phase was again hexane-isopropanol(4 l, or, also 19 1) and determination carried out at 254 or 280nm. The sulphoxides were better resolved on CSP 2. 

The applicability of cinchonan carbamate CSPs for bioanalytical investigations using HPLC-ESI-MS/MS has been demonstrated by Fakt et al. [120]. The goal was the stereoselective bioanalysis of (R)-3-amino-2-fluoropropylphosphinic acid, a y-aminobutyric acid (GABA) receptor agonist, in blood plasma in order to determine whether this active enantiomer is in vivo converted to the 5-enantiomer. In this enantioselective HPLC-MS/MS bioassay, sample preparation consisted of... 

Further, [2.2]paracyclophane-4-acetic acid, a potential drug candidate tested for its anti-inflammatory activity (NSAID could be resolved on the 0-9-(tert-butylcarbamoyl)quinine-based CSP with a = 1.12 Rs = 2.6) and elution order (R)-(-)- before (5)-(- -)-enantiomer [125]. Samples that were assessed to be enan-tiomerically pure by an enantioselective H-NMR spectroscopic method contained 6% and 8% enantiomeric impurity in S- and/ -enantiomers, respectively. This clearly reveals that enantioselective HPLC is a more powerful technique than NMR-methods to assess stereoisomeric purity, in particular, if the enantiomeric impurity amounts to less than 10%. 

ENANTIOSELECTIVE HPLC SEPARATIONS USING THE GLYCOPEPTIDES CONTAINING CSPs... 

A special mention in the field of enantioselective HPLC separations must be made of chiro-optical detection systems, such as circular dichroism (CD) and optical rotation (OR), which can be also used to circumvent the low UV detectability of chromophore-lacking samples [40, 61]. While sensitivity of chiro-optical detection is not always sufficient to perform enantiomeric trace analysis, the stereochemical information contained in the bisignate spectropolarimetric response is useful in establishing elution order for those compounds not available as single enantiomers of known configuration. An example of application of different online detection systems (UV and CD at 254 nm) in the enantioselective separation of a racemic sulfoxide on a commercially available TAG CSP is reported in Figure 2.12, under NP conditions. 

Ekborg-Ott, K.H., Liu, Y, and Armstrong, D.W., Highly enantioselective HPLC separations using the covalently bonded macrocyclic antibiotic, ristocetin A, chiral stationary phase. Chirality, 10, 434, 1998. 

Kleidernigg, O.P. and Kappe, C.O., Separation of enantiomers of 4-aryldihydropyrimidines by direct enantioselective HPLC. A critical comparison of chiral stationary phases. Tetrahedron Asymmetry, 8, 2057, 1997. 

Abd El-Hady, D. et al.. Methotrexate determination in pharmaceuticals by enantioselective HPLC, J. Pharm. Biomed. Anal., 31, 919, 2005. 

B. Blessington and A. Beiraghi, A method for the quantitative enantioselective HPLC analysis of ethambutol and its stereoisomers, Chirality, 3 139 (1991). 

Investigation on the enantiomeric composition of chiral secondary alcohols will, however, require either derivatization with an optically active reagent and separation on a conventional column or enantioselective GC using an optically active stationary phase. Today, the latter approach most frequently involves modified cyclodextrins.135 Enantioselective HPLC has also been successfully applied to separate enantiomers.136,137 Several reagents have been used in the transformation of chiral alcohols into diastereomers. Among these, acetyllactic acid138 or chlorofluoroacetic acid139 furnish volatile derivatives of pheromone... 

A chiral triether (syn-syn) with two different ether residues (Y1 = CH2C02Et Y2 = CH2C02CH2-pyrene, type AABH) has been obtained (55%) by direct alkylation of the corresponding monoether (K2C03/THF),120 and resolved by enantioselective HPLC (Chiracel OD). The excimer fluorescence of 58 increased up to twofold by addition of e.g. L-alanine methyl ester or L-phenylglycinol but no chiral discrimination was observed. 

A w-xylylene bridge connecting the oxygens in 1,3-position completely hinders the ring inversion. This was shown by Shinkai et al. for compound 83, which is chiral due to the methoxy group at the bridge.156 The racemate could be resolved by enantioselective HPLC (Chiralpak AD). No racemization was observed when a single enantiomer was heated to 100 °C (12 h, different solvents). 

The connection of adjacent phenolic units by directional bridges may be mentioned as an additional possibility. The C2-symmetrical lactone 102a is obtained in 36% yield from the tetrachloromethylated calix[4]arene tetrapropyl ether by reaction with salicylic acid. The formation of the Cs-symmetrical isomer is not observed in this case, probably since the most nucleophilic phenolate attacks at opposite rings, due to a pinched cone conformation of the tetrapropyl ether.196 In contrast, the similar cyclization with 3-hydroxymethyl-2-naphthol gave mainly the Cs isomer (Cs/C2 = 95/5). However, the C2 isomer 102b could be isolated and has been resolved by enantioselective HPLC (Chiralpak AD, a = 3.17).145... 

A 1,3-dimethylether of this type has been resolved by enantioselective HPLC Schmidt, C. Okamoto, J. Bohmer, V., unpublished results see below. 

Lammerhoffer, M. and Lindner, W., Optical purity determination of (R)- and (S)-econazole nitrate by enantioselective HPLC Method development and application, Poster presented at the 17th International Symposium on Column Liquid Chromatography, Hamburg 9th - 14th May, 1993. 

Subsequently, Figadere and coworkers30 analyzed natural rir-solamin by enantioselective HPLC, and found it to be a 9 8 mixture of rir-solamin A (36) and cis-solamin B (37). Thus, natural ar-solamin was stereochemi-cally heterogeneous demonstrating that enantioselective chromatography is indeed a powerful technique in... 

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