Enantioselectivity determination

The enantioselective determination of 2,2, 3,3, 4,6 -hexachlorobiphenyl in milk was performed by Glausch et al. (21). These authors used an achiral column for an initial separation, followed by separation of the eluent fraction on a chiral column. Fat was separated from the milk by centrifugation, mixed with sodium sulfate, washed with petroleum ether and filtered. The solvent was evaporated and the sample was purified by gel permeation chromatography (GPC) and silica gel adsorption chromatography. Achiral GC was performed on DB-5 and OV-1701 columns, while the chiral GC was performed on immobilized Chirasil-Dex. 

A. Glausch, J. Hahn and V. Schurig, Enantioselective determination of chiral 2,2, 3,3, 4,6-hexachlorohiphenyl (PCB 132), in human milk samples by multidimensional gas clnomatography/electi on capture detection and by mass spectrometiy , Chemosphere 30 2079-2085 (1995). 

Table 5-1. Enantioselectivities determined for several drugs. All experiments were performed at room temperature, except those marked with, which were performed at 4 °C. In some cases a lipophilic anion was used to facilitate the solubilization of the drug in the organic phases (PFj = hexafluorophosphate BPh = tetraphenyl borate). DHT = dihexyl tartrate DBT = dibenzoyl tartrate PLA = poly (lactic acid). ...

The latter approach is used in the enantioselective determination of a Phase I metabolite of the antihistaminic drug, terfenadine. Terfenadine is metabolized to several Phase I compounds (Fig. 7-13), among which the carboxylic acid MDL 16.455 is an active metabolite for which plasma concentrations must often be determined. Although terfenadine can be separated directly on Chiralpak AD - an amy-lose-based CSP - the adsorption of the metabolite MDL 16.455 is too high to permit adequate resolution. By derivatizing the plasma sample with diazomethane, the carboxylic acid is converted selectively to the methyl ester, which can be separated in the presence of all other plasma compounds on the above-mentioned CSP Chiralpak AD [24] (Fig. 7-14). Recently, MDL 16.455 has been introduced as a new antihistaminic drug, fexofenadine. 

Baser H-R, MD Muller (1993) Enantioselective determination of chlordane components, metabolites, and photoconversion products in environmental samples using chiral high-resolution gas chromatography and mass spectrometry. Environ Sci Technol 27 1211-1220. 

When the optically active catalyst [Rh((—)-BINAP)]+ was employed, a prochiral substrate was transformed to the corresponding chiral aldehyde with 18% ee (Scheme 23).45 Since the enantioselectivity-determining step in this... 

To examine the nature of the enatioselectivity of the catalysis we have examined the catalytic cycle with two substrates, styrene which leads to predominantly the R form of the product (64% ee) and 4-(dimethylamino)styrene which gives predominantly the S form of the product (67% ee). Our simulations suggest that the t 3-allylic coordination of the styrene substrate plays an important role in defining the enatioselectivity of the hydrosilylation. As a first step, this theoretical study constitutes a valid contribution in rationalizing the enantioselective determining factors and possibly in designing a new catalyst with improved enantioselective properties. We are currently examining nature of the enantioselectivity in more detail as well as the dependence of the enantioselectivity on the electronic nature of the substrates [58]. 

The enantioselectivity determining step. Above we learnt that the oxidative addition of hydrogen is the rate-determining step. This step is irreversible and it also determines the enantioselectivity. This complex could still epimerise via substrate dissociation, but apparently it does not and migratory insertion is faster than epimerisation. We remember that two diastereomeric intermediates are involved, the major and the minor species and the minor species is the... 

Boonen G, Beck MA, Haberlein H. (1997). Contribution to the quantitative and enantioselective determination of kavalactones by high-performance liquid chromatography on ChiraSpher NT material. J Chromatogr B Biomed Sci Appl. 702(1-2) 240-44. 

Aboul-Enein, H.Y. and Hefnawy, M.M., Enantioselective determination of arotino-lol in human plasma by HPLC using teicoplanin chiral stationary phase, Biomed. Chromatogr., 17, 453, 2003. 

Advantageously, in the context of subsequent synthetic manipulation, the acylated products in these processes are carbamates (rather than amides). Fu proposed a mechanistic pathway that involves rapid initial reaction of the catalyst with the 0-carbonyloxyazlactone to form an ion pair, followed by slow transfer of the methoxycarbonyl group from this ion-pair to the amine in the enantioselectivity determining step (Fig. 6) [99]. 

Capillary electrophoresis has been applied for the enantioselective determination of the binding constants of chiral drugs with cyclodextrins for basically the following two reasons (1) optimization of chiral selector concentration and (2) understanding the fine mechanisms of enantioseparations in CE. The first group of studies have been published mainly on the early stage of chiral CE development, whereas the second goal is followed in the most recent studies, mainly by Rizzi and Kremser (10,13) and Scriba et al. 

Enantioselective Determinations in Bulk Material and Pharmaceutical Eormulations.511... 

ENANTIOSELECTIVE DETERMINATIONS IN BULK MATERIAL AND PHARMACEUTICAL FORMULATIONS... 

Plasma is the most frequently analyzed matrix, and enantioselective determination of a parent drug for pharmacokinetic and therapeutic monitoring the most frequent goal of the developed methods but assays with simultaneous determination of metabolism are also common (Table 17.5). The majority of the methods are based on MS detection, and ESI is the predominant ionization... 

MIP films, applied to a QCM transducer, have been employed for chiral recognition of the R- and 5-propranolol enantiomers [107]. MIP films were prepared for that purpose by surface grafted photo-radical polymerization. First, a monolayer of 11-mercaptoundecanoic acid was self-assembled on a gold electrode of the quartz resonator. Then, a 2,2 -azobis(2-amidinopropane) hydrochloride initiator (AAPH), was attached to this monolayer. Subsequently, this surface-modified resonator was immersed in an ACN solution containing the MAA functional monomer, enantiomer template and trimethylolpropane trimethacrylate (TRIM) cross-linker. Next, the solution was irradiated with UV light for photopolymerization. The resulting MIP-coated resonator was used for enantioselective determination of the propranolol enantiomers under the batch [107] conditions and the FIA [107] conditions with an aqueous-ACN mixed solvent solution as the carrier. The MIP-QCM chemosensor was enantioselective to 5-propranolol at concentrations exceeding 0.38 mM [107]. 

Zavitsanos, A. P. Alebic-Kolbah, T. 1998. Enantioselective determination of terazosin in human plasma by normal phase high-performance liquid chromatography-electrospray mass spectrometry. / Chromatogr. A, 794, 45-56. 

Siluk D, Mager DE, Gronich N, Abernethy D, Wainer IW (2007) HPLC-atmospheric pressure chemical ionization mass spectrometric method for enantioselective determination of R, S-propranolol and R, S-hyoscyamine in human plasma. J Chromatogr B 859 213-221... 

The key NMR observations (i) that the proportion of homo- and heterochiral dimers is near-equal, and (ii) that their interconversion by a dissociative process is rapid compared to catalytic turnover, preclude the possibility of a monomer autocatalyst. In Kagan s classification, monomer catalysis with a positive NLE may only arise when there is an unequal concentration of homo- and heterochiral oligomers, in favour of the heterochiral form, which acts as a reservoir for the deficient enantiomer. NMR results show that the resting state for Soai s autocatalysis is an equal mixture of homo-and heterochiral species, predominantly dimeric. The lack of ground-state stereo-discrimination requires that the number of chiral entities in the resting state must be less than or equal to the number in the enantioselectivity-determining transition state, else there is no possibility of the vital non-linear effect. Even after the publication of these results in late 2004, their consequences are not always applied. For recent discussions where a monomeric catalyst for Soai s system is permitted or promoted, see [91-93]. 

Solvent CHjCN, styrene PhI=NTs = 5 1 molar ratio Isolated yield of aziridine based on PhI=NTs. Values in parentheses indicate yields obtained from homogeneous reactions Enantioselectivity determined by chiral HPLC styrene was used as solvent, e0 °C, f25°C, Absolute configurations of major products, determined by optical rotation, are (S) for trans-P-niethylstyrene and trans-P-methylcinnamate, (R) for styrene. 

Vetter, W. Schurig, V, Enantioselective determination of chiral organochlorine compounds in biota by gas chromatography on modified cyclodextrins 7. Chromatogr. A 1997,774,143-175. 

Vetter, W. Bartha, R. Stem, G. Tomy, G., Enantioselective determination of two persistent chlorobornane congeners in sediment from a toxaphene-treated Yukon lake Environ. Toxicol Chem. 1999, 18, 2115-21 1. 

Vetter, W. Luckas, B., Enantioselective determination of persistent and partly degradable toxaphene congeners in high trophic level hiota Chemosphere 2000, 41, 499-506. 

Schlauch, M., Fulde, K., Erahm, A.W. Enantioselective determination of (R)- and (S)-sotalol in human plasma by on-line coupling of a restricted-access material precolumn to a cellobio-hydrolase I-based chiral stationary phase. J. Chromatogr. B 775, 197-207 (2002)... 

Chromatographic enantioseparation of chiral xenobiotics and their metabolites is a versatile tool for process studies in marine and terrestrial ecosystems [235]. In 1994, three papers focused on the enantioselective determination of toxaphene components [120,236,237]. Buser and Muller found that technical toxaphene mixtures are not necessarily racemic [237]. This observation was supported after isolation of non-racemic B7-1453 from the product Melipax which had an excess of ca. 25% of the dextrorotary enantiomer [27, 238]. The enantioselective separation of toxaphene components is almost restricted to chiral stationary phases (CSPs) based on randomly derivatized ferf-butyldimethyl-silylated /1-cyclodextrin (commercially available from BGB Analytik, Adliswil, Switzerland). So far, only a few toxaphene components were enantioseparated on other CSPs [239, 240]. Some of these CSPs are not well defined as well, and for this reason a test mixture called CHIROTEST X was suggested for initial column testing [241],... 

The previously discus.sed thermodynamically controlled molecular recognition processes are the basis for a successful enantioseparation. However, from a separation methodological point of view, also the performance of the separation system has to be considered, which in addition to the thermodynamically controlled enantioselectivity determines the peak resolution () which is a measure for the quality of a separation. 

---