Chiral chromatographic studies

The need to develop and use chiral chromatographic techniques to resolve racemates in pesticide residues will be driven by new hazard and risk assessments undertaken using data from differential metabolism studies. The molecular structures of many pesticides incorporate chiral centers and, in some cases, the activity differs between enantiomers. Consequently, in recent years manufacturers have introduced resolved enantiomers to provide pesticides of higher activity per unit mass applied. For example, the fungicide metalaxyl is a racemic mix of R- and 5-enantiomers, both having the same mode of action but differing considerably in effectiveness. The -enantiomer is the most effective and is marketed as a separate product metalaxyl-M. In future, it will not be satisfactory to rely on hazard/risk assessments based on data from metabolism studies of racemic mixes. The metabolism studies will need to be undertaken on one, or more, of the resolved enantiomers. 

Accordingly, Siluk et al. performed chiral chromatographic APCI-MS analysis of human plasma samples obtained from a PK study after administration of atropine sulphate (10 ug/kg as initial i.v. bolus followed by 30 min infusion of 20 pg/kg) [48], Peak plasma concentrations of both enantiomers were not reported in detail but were presumably about 5 ng/ml as deduced from the illustrated concentrationtime profile. The authors found that. S -hyoscyaminc was eliminated slightly faster than //-hyoscyaminc. 

R. K. Gilpin, S. E. Ethesham, and R. B. Gregory, Liquid chromatographic studies of the effect of temperature on the chiral recognition of tryptophan by silica-immobilized bovine albumine, A a/. Chem. 63 (1991), 2825. 

Some optically active cationic and racemic anionic complexes were examined to elucidate the mechanism of chiral recognition of cations and anions capable of forming hydrogen bonds [313]. The chromatographic study showed that enantiomers of some anionic complexes form favourable ion pairs with cationic A-complexes (Table 31). 

In the course of the development of CSPs, a broad variety of chiral molecules (and materials) has been the subject of scrutiny with respect to chromatographic enantiomer separation capacity. The chiral molecules studied as potential SOs cover virtually the entire chemical and structural diversity space, ranging from low-molecular-weight compounds to polymers of both synthetic and biological origin. So far, the (stiU ongoing) quest for efficient SOs has resulted in the synthesis of more than 1400 CSPs [94], the properties of which are documented in an almost intractable number of dedicated scientific publications. The outcome of these efforts is manifest in an enormously rich toolbox of more than 200 commercially available CSPs offered by various speciahzed suppliers. 

Tabun has a stereogenic (chiral) phosphoms atom and exists as a pair of enantiomers. A gas chromatograph study of the enantiomers of tabun has been reported (Degenhardt et al., 1986). Separation was achieved through the use of bis[(l/f)-3-(heptafluorobutyryl-camphorate)nickel(II). This approach also separated stereoisomers of both sarin and soman. These authors also reported the stereospecific hydrolysis of racemic tabun using phosphorylphosphatases. They noted the species (mouse, rat, horse) dependence of the hydrolysis. Dilute solutions of tabun in inert solvents (e.g., carbon tetrachloride) exhibit optical stability for months at — 25°C. 

Van Overbeke, A. Baeyens, W. Van Der Weken, G. Van de Voorde, I. Dewaele, C. Comparative chromatographic study on the chiral separation of the 1-naphthylamine derivative of ketoprofen on cellulose-based columns of different sizes. Biomed.Chromatogr., 1995, 9, 289-290... 

Hayball, P.J. Holman, J.W. Nation, R.L. Influence of octanoic acid on the reversible protein binding of ketorolac enantiomers to human serum albumin (HSA) comparative liquid chromatographic studies using a HSA chiral stationary phase. J.ChromatognB, 1994, 662, 128-133 [chiral]... 

Roussel and Popescu [54] extended this work by developing a lipophilicity parameter, log k w The authors were able to explain the relationship between chiral retention of the enantiomers and their lipophilic interactions with the CSPs. Quantification of the influence of structural parameters Xi, X2 and X3 was also possible. The relationship between lipophilicity and chiral chromatographic behavior was explained for compounds 23-30 and an extension to other alkyl substituted atropisomers was made. A related study concerning the resolution of 23-30 on various p-methylbenzoyl cellulose beads has also been published [55] but will not be described here because it employs the same methodology as above. 

N.A. Kamik, R.J. Prankerd and J.H. Perrin, Fluorometric and Liquid Chromatographic Study of the Binding of Two Coumarins to P-Cyclodextrin, Chirality, 3(1991)124. 

But, the a-, P- and y-HBCD diastereoisomers are chiral and because of that must be present in the environment as enantiomeric pairs. The enantiomers have identical physicochemical properties and abiotic degradation rates, but may have different biological and toxicological properties and therefore different biotransformation rates. These transformations may result in non-racemic mixtures of the enantiomers that were industrially synthesized as racemates. A chiral chromatographic coliunn must be used in order to obtain an enantiomeric separation. All recent studies showed a good separation using a Nucleodex j8-PM (4.0 mm x 200 mm x 5 p,m) [68-70]. A representative chromatogram of a standard mixture of three diastereomers of HBCD... 

The many data which have accumulated through chromatographic studies of resolution permit a) to single out systems which seem suitable for more detailed investigations of the intimate molecular mechanism of chiral recognition by methods such as X-ray crystallography and b) to correlate the influence of structural factors of selectors and selectands on stereoselectivity. 

Chiral 1,5-diols (153) have been efficiently accessed by iridium-catalysed asymmetric hydrogenation of 6-aryl-5-ketoesters (152). A gas chromatographic study indicates 0 initial ketone reduction, to the hydroxyl-ester. Loss of ethanol gives a 5-lactone intermediate, which is reductively reopened this sequence is confirmed by generation of (153) when an authentic sample of the lactone is treated under the same conditions. 

In this chapter, the application of CILs in various fields has been discussed. This is with particular focus on the chiral chromatographic separations and spectroscopic discrimination. Chiral recognition and separation mechanism using CILs so far have not been thoroughly studied. This chapter discusses the enantiomeric discrimination mechanism using CILs as chiral selectors from some preliminary results. 

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