Racemic compounds separation

Table 2. Retention Data for Racemic Compounds Separated on a p-Cyclodextrin Stationary Phase ...

Racemic compounds separated using alkylated CF6 as the selector in GC includes P-lactams, trifluoroacetyl derivatized amino acids, and tartaric acid esters [47]. Hydrogen bonding is of critical importance for enantiomeric separations in GC. On permethylated CF6, a-(trifluoromethyl)benzyl alcohol was baseline separated, whereas esters of this alcohol were less retained and no separation was observed (Table 3). Furthermore, no separation was observed for native a-methylbenzyl alcohol, which is a weaker hydrogen bond donor than a-(trifluoromethyl)benzyl alcohol. Likewise, enantiomers of A-acetylated amino acids were poorly separated or not separated, whereas A-trifluoroacetylated amino acids are very well separated [47]. 

The racemic acid is not a primary product of plant processes but is formed readily from the dextrorotatory acid by heating alone or with strong alkaU or strong acid. The methods by which such racemic compounds can be separated into the optically active modifications were devised by Pasteur and were apphed first to the racemic acid. Racemic acid crystallizes as the dihydrate triclinic prisms. It becomes anhydrous on drying at 110°C... 

The first observation of the enantioselective properties of an albumin was made in 1958 (28) when it was discovered that the affinity for L-tryptophan exceeded that of the D-enantiomer by a factor of approximately 100. This led to more studies in 1973 of the separation of DL-tryptophan [54-12-6] C22H22N2O2, on BSA immobilized to Sepharose (29). After extensive investigation of the chromatographic behavior of numerous racemic compounds under different mobile-phase conditions, a BSA-SILICA hplc column (Resolvosil-R-BSA, Macherey-Nagel GmvH, Duren, Germany) was... 

The type of CSPs used have to fulfil the same requirements (resistance, loadabil-ity) as do classical chiral HPLC separations at preparative level [99], although different particle size silica supports are sometimes needed [10]. Again, to date the polysaccharide-derived CSPs have been the most studied in SMB systems, and a large number of racemic compounds have been successfully resolved in this way [95-98, 100-108]. Nevertheless, some applications can also be found with CSPs derived from polyacrylamides [11], Pirkle-type chiral selectors [10] and cyclodextrin derivatives [109]. A system to evaporate the collected fractions and to recover and recycle solvent is sometimes coupled to the SMB. In this context the application of the technique to gas can be advantageous in some cases because this part of the process can be omitted [109]. 

E. Erancotte, Chromatography as a separation tool for the preparative resolution of racemic compounds in Chiral separations, applications and technology, S. Ahuja (Ed.), American Chemical Society, Washington (1997) Chapter 10. 

Statistically, of the compounds enantioresolved by macrocyclic glycopeptide CSPs, new polar organic mode accounts for more than 40 %, balanced by reversed-phase mode, while typical normal-phase operation resulted in approximately 5 % of separations. Some categories of racemic compounds that are resolved on the glycopeptide CSPs at different operating modes are listed in Table 2-4. 

Our strategy consisted of the following steps A mixture of potential chiral selectors is immobilized on a solid support and packed to afford a complete-library column , which is tested in the resolution of targeted racemic compounds. If some separation is achieved, the column should be deconvoluted to identify the selector possessing the highest selectivity. The deconvolution consisted in the stepwise preparation of a series of sublibrary columns of lower diversity, each of which constitute a CSP with a reduced number of library members. 

Erancotte E. (1996) Chromatography as a Separation Tool for the Preparative Resolution of Racemic Compounds, in Chiral Separations. Applications and Technology, Ahuja S. (ed.), American Chemical Society, p. 271-308. 

The enantiomers of many compounds are eluted in reverse order on the 3,5-dimethylphenylcarbamates of cellulose (23x) and amylose (24n), suggesting that these two CSPs may be complementary in recognizing chirality. Many enantiomers unresolved on 23x can be resolved on 24n, and vice versa. Consequently, when two 23x and 24n columns were used for the resolution of 500 racemates, nearly 80% of the racemates were separated into enantiomers at least on either of 23x and 24n. 

A complete separation of the isomers is not possible by this method because it is not always easy to find a suitable mould or bacterium for each and every racemic compound. Therefore, the method suffers from the following defects ... 

Finally, reference must be made to the important and interesting chiral crystal structures. There are two classes of symmetry elements those, such as inversion centers and mirror planes, that can interrelate. enantiomeric chiral molecules, and those, like rotation axes, that cannot. If the space group of the crystal is one that has only symmetry elements of the latter type, then the structure is a chiral one and all the constituent molecules are homochiral the dissymmetry of the molecules may be difficult to detect but, in principle, it is present. In general, if one enantiomer of a chiral compound is crystallized, it must form a chiral structure. A racemic mixture may crystallize as a racemic compound, or it may spontaneously resolve to give separate crystals of each enantiomer. The chemical consequences of an achiral substance crystallizing in a homochiral molecular assembly are perhaps the most intriguing of the stereochemical aspects of solid-state chemistry. 

Ondansetron (17) is a racemic compound not easy to resolve by chemical means because the carbonyl function is poorly reactive so it is difficult to form chiral derivatives. However, a resolution was achieved by the classical method of forming diastereomeric salts with an optically active acid and then separating the salts by recrystallisation. A number of acids were tried, but only the salts prepared from (-f)- and (—)-di-p-toluoyltartaric acid could be separated in this way. Each isomer was obtained in greater than 95 %ee. The absolute stereochemistry of the isomer from the (-E)-acid was determined by X-ray crystallography (Williams, D., personal communication) and shown to possess the 5-configuration (18). 

Partial or complete separation of enantiomers within a racemic mixture as a result of unequal rates of reaction with another agent. The latter reagent, catalyst, solvent, or micelle must itself exhibit chirality, resulting in its stereoselective or stereospecific action on the racemic compound. 

The reasons for these choices are as follows. For most practical purposes a compound of a reasonably high degree of enantiomeric purity is the desired goal of an enantiosclcctivc reaction. The most convenient way to achieve this result is by recrystallization of the product or a derivative. This process, in the majority of cases, involves separation of the pure enantiomer from the racemate. The ee value, being equivalent to the percentage of the major isomer in the mixture with the racemic compound, defines the maximum yield of the pure isomer that can... 

Additional enantiomerically pure 4,5-dihydroisoxazoles are prepared by separation of racemic compounds via chiral sulfoxides5-8, or by microbial reduction of 5-acetyl-4,5-di-hydroisoxazoles 34. 

It is long since that the resolution of low-molecular-weight racemic compounds by elution chromatography on optically active supports was known (58) however only recently vinyl-polymers obtained from racemic monomers have been separated in fractions having optical activity of opposite sign by this technique (106). 

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