Barbiturates chiral resolution

The effect of various SFC parameters on chiral resolution were also studied. Modifiers can provide control over both retention and selectivity and, therefore, certain modifiers were used to optimize the separation in sub-FC and SFC. The effect of the enantioselectivity of carbon dioxide on acidic drugs (benzoxaprofen, temazepam, and mephobarbital), profen, and barbiturate derivatives was carried out on Chiralcel OJ, with acetonitrile or methanol as organic modifier [140]. Acetonitrile proved to be a good alternative to methanol, especially for the profen compounds that were not well resolved when methanol was used. Wilson [143] studied the effects of methanol, ethanol, and 2-propanol as organic modifiers on the chiral resolution of ibuprofen on Chiralpak AD CSPs. Methanol was found to be the best organic modifier. 

The application of antibiotics as chiral selectors has resulted in the successful resolution of almost all types of neutral, acidic, and basic racemic molecule. These antibiotics have been used for the enantiomeric resolution of amino acids, their derivatives, peptides, alcohols, and other pharmaceuticals. The selectivities of the most commonly used antibiotic-based (vancomycin, teicoplanin, and ristocetin A) CSPs varied from one racemate to another and are given in Table 1. Vancomycin was used for the chiral resolution of amino acids, amines, amides, imides, cyclic amines, amino alcohols, hydantoins, barbiturates, oxazolidinones, acids, profens, and other pharmaceuticals. Teicoplanin was found to be excellent chiral selector for the enantiomeric resolution of amino acids, amino alcohols, imides, peptides, hydantoins, a-hydroxy and halo acids, and oxazolidinones, whereas ristocetin A is capable of chiral resolution of amino acids, imides, amino... 

The applications of re-acidic chiral stationary phases include the resolution of a-blockers and /1-blockers, amines, arylacetamine, alkylcarbinols, hydantoins, barbiturates, naphthols, benzodiazapines, carboxylic acids, lactams, lactones, phthaldehydes selenoids, and phosphorus compounds. Hyun et al. [16] achieved a chiral resolution of a homologous series of iV-acyl-x-(l-naphthyl )cthylaminc on AA(3,5-dinitrobenzoyl-(i )-phenylglycine and N-(3,5 - dini tr o ben zoy I)-(,S ) -1 c u c ine CSPs. The authors used hexane-2-propanol (80 20, v/v) as the mobile phase. Similarly, the scope of re-basic CSPs comprises the chiral resolution of / -blockers, amino acids, amines, diamines, amino phosphonates, naphthols, benza-diazapines, carboxylic acids, hydroxy acids, dipeptides, tripeptides, diols,... 

TABLE 3 Effect of Substituents on the Chiral Resolution of Barbiturates (Fig. 11) on the BSA-Based CSP Using Phosphate Buffer (50mM, pH 5.8)-l-Propanol (94 6, v/v) as the Mobile... 

The mechanism of retention on chiral phases that is based on multiple hydrogen bonding formation involves the formation of base pairs and triple hydrogen bonds between the solutes and the chiral stationary phase 95 Fundamental work in this area has been done by Hara and Dobashi,96 97 using amino acid amide and tartaric acid amide phases. In addition, N,N -2,6-pyridinediyl bis(alkanamides) chemically bonded to silica gel have been described for the resolution of barbiturates 95... 

Figure 9 shows the examples of separations of racemic mixtures of methylphenobarbital and mephenytoin performed under optimal conditions available (37). It has been found that ( -CD complexation resuTts in a distinct enantioselectivity in the case of mephenytoin and barbiturates which have a chiral center in the pyrimidine ring. The resolution of barbiturate enantiomers is due to the different stabilities of their diastereo-isomeric -CD complexes, while the separation of mephenytoin enantiomers results from the difference in their adsorption on the RP phase. The latter case should be considered further. It has been already suggested (18) that the adsorption of CD complexes in which guest molecules are entirely immersed in the CD cavity is low on RP phases. The distinct adsorption arises from the part of the molecule which is outside the cavity. Taking into account this fact and the remarkable difference in the adsorption of -CD mephenytoin diastereoisomers one may conclude that a significant difference must exist between immersion of mephenytoin enantiomers in the -CD cavity. 

Zukowski, J. Sybilska, D. Bojarski, J. Szejtli, J. Resolution of chiral barbiturates into enantiomers by reversed-phase high-performance hquid chromatography using methylated P-cyclodextrins. J. Chromatogr. 1988,463 (3), 381-390. 

Dauwe and Buddrus [12] tested a series of chiral amines for their ability to discriminate between the enantiomers of several acidic compounds. Strong basic amidines, as shown in Figure 6-8, turned out to be suitable for the resolution of even weak acidic compounds such as phenols, barbiturates and alcohols. The same group [13] developed chiral palladium complexes with diamines for discrimination of a-amino acids and determination of enantiomeric excess resulting from asymmetric synthesis. 

Chiral surfactants used in MEEKC have also been like dodecoxycarbonylvaline (DDCV) for the separation of different enantiomeric analytes [46,47]. Chiral polymeric surfactant has been also employed in the enantiomeric resolution of barbiturate, binaphthyl, and paveroUne [48],... 

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