Chirality/Chiral plates

Gas chromatography (gc) is inferior to hplc in separating abiUty. With gc, it is better to use capillary columns and the appHcation is then limited to analysis (67). Resolution by thin layer chromatography or dc is similar to Ic, and chiral stationary phases developed for Ic can be used. However, tic has not been studied as extensively as Ic and gc. Chiral plates for analysis and preparation of micro quantities have been developed (68). 

A complementary approach is to use reverse phase silica gel impregnated with a chiral selector [55,56]. Chiral plates comprising reverse phase Cjg impregnated with copper A,Ar-dialkyl-a-amino acids, e.g. proline have been used successfully for the separation of a variety of enantiomeric mixtures, e.g. d- and L-dopa. The resolution is based on ligand exchange, the enantiomers to be separated forming chelate complexes with the copper ion of differing stabilities. 

Fig. 1 Classes of chiral organic compounds resolved (A) by ligand exchange chromatography on Chiral plate and HPTLC Chir plates and (B) on MCTA layers.

In CSPs, owing to the nature of the polymer structure, the simultaneous participation of several chiral sites or several polymer chains is conceivable. In CCSPs, the chiral sites are distributed on the surface or in the network of the achiral matrix relatively far away from each other, and only bimolecular interaction is generally possible with the optical antipodes. A survey of the optically active substance classes separated with Chiral plate and HPTLC Chir layers and with microcrystalline cellulose triacetate (MCTA) plates is shown in Fig. 1. Cellulose tribenzoate and tricarbamate have recently been used for the separation of enantiomeric aromatic alcohols, Troger s base, and benzoin ethyl ether. 

The overwhelming majority of chiral separations up to now have been carried out by adding various chiral selectors to the mobile phase rather than by using a chiral plate. For example, enantiomers of amino acids were separated by using alpha- and beta-cyclodextrins as mobile phase additives with bonded Cig and cellulose layers (Cserhati and Forgacs, 1996). 

Pyka (1993) developed a new topological index for predicting the separation of D and L optical isomers of amino acids on chiral plates. LeFevre (1993) used reversed-phase TLC to separate dansyl-amino acid enantiomers. Das and... 

Feldberg and Reppucci developed a novel separation of anomeric alpha (pharmacologic) purines carried out by copper acetate chiral plates. Solvents were methanol-water-ACN. Visualization occurred through UV. Graphs were plotted based on alteration of ACN percentages. 

In a recent publication, Sliwiok et al. (50) separated D and L enantiomers of a-tocopherol on chiral plates that were activated at 1(X)°C for 15 min. The mobile phase consisted of a mixture of 2-propanol-water-methanol (8.5 1.0 0.5, by vol). The Revalues were 0.62 and 0.72, respectively. 

The chiral plates are used extensively for the enantiomeric separation of racemic amino acids and their derivatives by means of a ligand exchange mechanism. 

Chapter 3 through 6 deal with the commercial and noncommercial stationary phases used for the direct and indirect enantioseparations by means of TLC and with the chiral modifiers of mobile phases, which are used exclusively in direct separations. Chapter 3 describes the commercial chiral and nonchiral sorbent materials and commercial precoated layers used in chiral separations. Thus, it deals with silica gel native and esterified cellulose chiral plates (reversed phase plates impregnated with a chiral selector) and C-18, C-18W, diol, diphenyl, and C-2 chemically bonded silica gel. At the end of this chapter, the author discusses the quantification of enantiomers by using densitometry, depending on the type of the stationary phase employed. 

The first chiral plates were those on cellulose [4-6], which were used to obtain the same paper chromatographic separations [1,7-9]. In particular, in 1965, Contractor and Wragg [4] prepared cellulose homemade plates (20 x 20 cm Whatman, USA) to resolve racemic amino acids. Later, other researchers [5] used noncommercial microcrystalline cellulose plates (20 x 20 cm) to separate optical isomers of tryptophan and kynurenine, and their derivatives (see Table 4.1). All the investigated racemates were well resolved showing a-values in the range 1.13 to 1.60. The enantiomeric amino acid sequence was reversed by changing the kind of the eluent. 

It should also be mentioned that Szulik and Sowa [44] successfully separated enantiomers of some fatty hydroxyl acids such as DL-a-hydroxypalmitic- and DL-12-hydroxy stearic acid using 1% L-alanine and 2% L-alanine as mobile phase additives, respectively, with silica gel plates serving as a stationary phase. Besides, these authors presented enantioseparation of DL-12-hydroxyoleic acid using chiral plates [44]. 

SEPARATION OF AMINO ACID ENANTIOMERS ON THE COMMERCIAL CHIRAL PLATES... 

The h/ F values and conditions of separations of racemates on commercial chiral plates by LEC are collected in reviews by different authors amino acids [1,7,8,11], a-substituted of the amino acids [7,8,11], dipeptides [7,8], j8-methyl derivatives of amino acids [7,11,19], a-dialkyl amino acids [1], other derivatives — fluoro, bromo, benzyl, etc. [1,7,8,11]. 

Inspired by the separation ability of cyclic selectors such as cyclodextrins and crown ethers, Malouk s group studied the synthesis of chiral cyclophanes and their intercalation by cation exchange into a lamellar solid acid, a-zirconium phosphate aiming at the preparation of separation media based on solid inorganic-organic conjugates for simple single-plate batch enantioseparations [77-80]. 

Stalcup aiid co-workers [14] adapted this method to a continuous elution mini-prep electrophoresis apparatus shown in Fig. 11-3. In this apparatus, the end of the electrophoretic gel is continuously washed with elution buffer. The eluent can then be monitored using an HPLC detector (Fig. 11-4) and sent to a fraction collector where the purified enantiomers, as well as the chiral additive, may be recovered. In this system, the gel configuration was approximately 100 mm x 7 mm, and was aircooled. The number of theoretical plates obtained for 0.5 mg of piperoxan with this gel was approximately 200. A larger, water-cooled gel was able to handle 15 mg of... 

There are very few examples of asymmetric synthesis using optically pure ions as chiral-inducing agents for the control of the configuration at the metal center. Chiral anions for such an apphcation have recently been reviewed by Lacour [19]. For example, the chiral enantiomerically pure Trisphat anion was successfully used for the stereoselective synthesis of tris-diimine-Fe(ll) complex, made configurationally stable because of the presence of a tetradentate bis(l,10-phenanthroline) ligand (Fig. 9) [29]. Excellent diastereoselectivity (>20 1) was demonstrated as a consequence of the preferred homochiral association of the anion and the iron(ll) complex and evidence for a thermodynamic control of the selectivity was obtained. The two diastereoisomers can be efficiently separated by ion-pair chromatography on silica gel plates with excellent yields. 

A simple and rapid method of separating optical isomers of amino acids on a reversed-phase plate, without using impregnated plates or a chiral mobile phase, was described by Nagata et al. [27]. Amino acids were derivatized with /-fluoro-2,4-dinitrophenyl-5-L-alanine amide (FDAA or Marfey s reagent). Each FDAA amino acid can be separated from the others by two-dimensional elution. Separation of L- and D-serine was achieved with 30% of acetonitrile solvent. The enantiomers of threonine, proline, and alanine were separated with 35% of acetonitrile solvent and those of methionine, valine, phenylalanine, and leucine with 40% of acetonitrile solvent. The spots were scraped off the plate after the... 

Figure 7.9 A, ScheMtic representation of cosplex fomtlon between an anlno acid and copper in the presence of a diysically inaobllized chiral selector. B, separation of D-leu-L-leu(l) and L-leu-D-leu(2) on a CHIR plate with aethanol-propan-l-ol-vater (5 1 4) as the mobile phase with detection at 410 na. (Reproduced with permission from ref. 109. Copyright Dr. Alfred Huethig Publishers).

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