Enantioselective related techniques

Pais, LS., Mata, V.G., Rodrigues, A.E. (2005) Simulated moving bed and related techniques, in Preparative Enantioselective Chromatography, 1st edn (ed. G.B. Cox), Wiley-Blackwell,... 

Enantioselective chromatography and related techniques are based principally on the reversible formation of diastereomeric associates between both enantiomers of the chiral analyte (selectand, SA) and the chiral selector (SO) that is usually covalently immobilized or coated on a solid support (Figure 13.9). 

Of the two related techniques, FAB found far greater use in studies of enantioselective discrimination as compared to other desorption/ionization methods, such as MALDI and secondary ion mass spectrometry (SIMS). Chan and coworkers demonstrated enantiodiscrimina-tion of amino acids by a-, P-, and y-cyclodextrins using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) [28]. The observed levels of enantioselectivity were found to be dependent on the size of cyclodextrin cavities, as well as on the length and functionality of the amino acid side chain. Vairamani and coworkers demonstrated discrimination of amino acid methyl esters using various monosaccharide hosts by liquid secondary ion mass spectrometry (LSIMS) [29]. It is curious that more work has not been done using these sources. MALDI, in particular, is a simple and straightforward technique. Various researchers have demonstrated the observation of noncovalent complexes [30-32], for example, between peptides and proteins, but relatively little work has been performed that focuses on studying enantioselective noncovalent interactions by MALDI-MS. 

In simple experiments, particulate silica-supported CSPs having various cin-chonan carbamate selectors immobilized to the surface were employed in an enantioselective liquid-solid batch extraction process for the enantioselective enrichment of the weak binding enantiomer of amino acid derivatives in the liquid phase (methanol-0.1M ammonium acetate buffer pH 6) and the stronger binding enantiomer in the solid phase [64]. For example, when a CSP with the 6>-9-(tcrt-butylcarbamoyl)-6 -neopentoxy-cinchonidine selector was employed at an about 10-fold molar excess as related to the DNB-Leu selectand which was dissolved as a racemate in the liquid phase specified earlier, an enantiomeric excess of 89% could be measured in the supernatant after a single extraction step (i.e., a single equilibration step). This corresponds to an enantioselectivity factor of 17.7 (a-value in HPLC amounted to 31.7). Such a batch extraction method could serve as enrichment technique in hybrid processes such as in combination with, for example, crystallization. In the presented study, it was however used for screening of the enantiomer separation power of a series of CSPs. 

Similar equations can be written for both enantiomers of chiral analyte. Based on Eq. (14), nonlinear regression techniques allow one to determine the enantioselective binding constants (KR and Ks) and the mobilities of related transient diastereomeric complexes (/4°mplex and /x ""plex). 

Several other practical syntheses of enantiopure amino acid derivatives have been accomplished recently from substrate 35 (Chart 10.6). The Imperiali group has used two techniques following PTC alkylations that occurred with modest enantioselectivity (50-53% ee). The first involved fractional recrystallization followed by subsequent deprotection/reprotection to give 39 (>99% ee). In the second method, enzymatic hydrolysis of the amino acid methyl ester with alkaline protease and then nitrogen acylation gave 40 (99% ee) [16]. Several other publications that deal with related purification techniques have appeared [17-19]. 

Enantioselectivity was introduced especially for use in analysis of pharmaceuticals, where it was found that some pharmaceutical products have a chiral center and only one of the enantiomers exhibits the required pharmacological and pharmacokinetic behavior. The term was introduced first in relation to separation techniques,278 281 and later sensor technology.282... 

The stereochemical correlations between the enantiomorphic crystals and their chiral inhibitors, namely that the additive affects only the enantiomer of the same absolute configuration, provides us with a new method for the determination of absolute configuration on a relative scale. This is revealed independently by morphological changes and enantioselective occlusion of additives. The method is related to the quasi-racemate technique of Fredga [18], but has the advantage of a wider applicability. 

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