Enantiomers chemical separation

For initial work on cyclodextrin-mediated chromatographic separation of enantiomers, see Hinze, W. L. Armstrong, D. W. ed. Ordered Media in Chemical Separations, ACS Symposium Series 342, 1986. 

Aspartame is synthesized using the L enantiomer of phenylalanine. The L enantiomer is separated from the D enantiomer, the racemic mixture, by reacting it with acetic anhydride (CH3C0)20) and sodium hydroxide. The product of this reaction is then treated with the enzyme porcine kidney acylase. An organic extraction with acid yields the L enantiomer in the aqueous layer and the D enantiomer in the organic layer. The L-phenylalanine is reacted with methanol and hydrochloric acid to esterify the COOH group on phenylalanine. The esterified L-phenyalanine is then reacted with aspartic acid, while using other chemicals to prevent unwanted side reactions, to produce aspartame. 

An optimized version of the enantioselective SMB-GC unit was subsequently presented for enflurane enantiomers (chemical structure cf. insert in Figure 24) (Biressi et al., 2002b). It consisted of eight 80 cm x 15 mm (i.d.) stainless steel columns assembled in a home-made SMB-GC unit operated at 35°C (Scheme, cf. Figure 24). Each column with an adsorption bed volume of 140 ml each contained 20 % unpurified Lipodex E in the polysiloxane SE-54 and coated (17 %, w/w) on Chromosorb A (NAW, 20-30 mesh) 0.6 mm). This set-up represented the first gas-chromatographic SMB-GC unit for the preparative-scale separation of enantiomers. 

The use of homochiral complexation agents to separate the fluorine-19 chemical shifts of enantiomers containing fluorine has also been examined. Addition of the supported dipeptide 9 to a solution of the racemic iV-acylamino acid ester 10 in carbon tetrachloride leads to the appearance of two CF3 peaks corresponding to the two enantiomers. The separation is obviously concentration-dependent, but peak separation was sufficient for mixtures of enantiomers to give enantiomeric excesses comparable with those determined by gc analysis55. 

A vast number of aldehydes have so far been used as substrates of this set of aldolases in preparative experiments [20, 24, 25, 190). With the exception of generic aldehydes, acceptor components must be prepared by chemical synthesis. In general, ozonolysis of suitable olefins (with appropriate removal of the second fragment if this also is a substrate) or acidotalyzed acetal deprotection are convenient routes for generation of aldehyde substrates under mild conditions. Chiral aldehydes require either asymmetric synthesis of the respective enantiomer or separation of diastereomeric products produced from racemic material. In specific cases racemate resolution can be effected by the enantiomer selectivity of an aldolase (kinetic resolution Figure 5.27) or when isomeric products have significantly different stability (thermodynamic resolution vide infra). 

Resolution of racemates through the diastereomer formation and selective crystallization is a common strategy for chemical separation of enantiomers from racemic mixtures employing chiral resolving agents. The principle of a... 

Chemical separation of enantiomers viadiastereoisomers, which can be formed in reactions with optically pure reagents or by using nonspecific bonds in complexes or inclusive conjugates [42]. 

An example of a chiral compound is lactic acid. Two different forms of lactic acid that are mirror images of each other can be defined (Figure 2-69). These two different molecules are called enantiomers. They can be separated, isolated, and characterized experimentally. They are different chemical entities, and some of their properties arc different (c.g., their optical rotation),... 

A few GLC stationary phases rely on chemical selectivity. The most notable are stationary phases containing chiral functional groups, which can be used for separating enantiomers. ... 

There are interesting examples of enantiomers that not only are found separately but also have different chemical properties when reacting with some reagent which is itself an enantiomer. For example (+ )-glucose is metabolized by animals and can be fermented by yeasts, but (—)-glucose has neither of these properties. The enantiomer ( + )-carvone smells of caraway whereas (—)-carvone smells of spearmint. 

Traditionally, chiral separations have been considered among the most difficult of all separations. Conventional separation techniques, such as distillation, Hquid—Hquid extraction, or even some forms of chromatography, are usually based on differences in analyte solubiUties or vapor pressures. However, in an achiral environment, enantiomers or optical isomers have identical physical and chemical properties. The general approach, then, is to create a "chiral environment" to achieve the desired chiral separation and requires chiral analyte—chiral selector interactions with more specificity than is obtainable with conventional techniques. 

Enzymatic hydrolysis is also used for the preparation of L-amino acids. Racemic D- and L-amino acids and their acyl-derivatives obtained chemically can be resolved enzymatically to yield their natural L-forms. Aminoacylases such as that from Pispergillus OTj e specifically hydrolyze L-enantiomers of acyl-DL-amino acids. The resulting L-amino acid can be separated readily from the unchanged acyl-D form which is racemized and subjected to further hydrolysis. Several L-amino acids, eg, methionine [63-68-3], phenylalanine [63-91-2], tryptophan [73-22-3], and valine [72-18-4] have been manufactured by this process in Japan and production costs have been reduced by 40% through the appHcation of immobilized cell technology (75). Cyclohexane chloride, which is a by-product in nylon manufacture, is chemically converted to DL-amino-S-caprolactam [105-60-2] (23) which is resolved and/or racemized to (24)... 

Separation of enantiomers by physical or chemical methods requires the use of a chiral material, reagent, or catalyst. Both natural materials, such as polysaccharides and proteins, and solids that have been synthetically modified to incorporate chiral structures have been developed for use in separation of enantiomers by HPLC. The use of a chiral stationary phase makes the interactions between the two enantiomers with the adsorbent nonidentical and thus establishes a different rate of elution through the column. The interactions typically include hydrogen bonding, dipolar interactions, and n-n interactions. These attractive interactions may be disturbed by steric repulsions, and frequently the basis of enantioselectivity is a better steric fit for one of the two enantiomers. ... 

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