Extraction enantioselective

Early examples of enantioselective extractions are the resolution of a-aminoalco-hol salts, such as norephedrine, with lipophilic anions (hexafluorophosphate ion) [184-186] by partition between aqueous and lipophilic phases containing esters of tartaric acid [184-188]. Alkyl derivatives of proline and hydroxyproline with cupric ions showed chiral discrimination abilities for the resolution of neutral amino acid enantiomers in n-butanol/water systems [121, 178, 189-192]. On the other hand, chiral crown ethers are classical selectors utilized for enantioseparations, due to their interesting recognition abilities [171, 178]. However, the large number of steps often required for their synthesis [182] and, consequently, their cost as well as their limited loadability makes them not very suitable for preparative purposes. Examples of ligand-exchange [193] or anion-exchange selectors [183] able to discriminate amino acid derivatives have also been described. 

In the classical set-up of bulk liquid membranes, the membrane phase is a well-mixed bulk phase instead of an immobilized phase within a pore or film. The principle comprises enantioselective extraction from the feed phase to the carrier phase, and subsequently the carrier releases the enantiomer into the receiving phase. As formation and dissociation of the chiral complex occur at different locations, suitable conditions for absorption and desorption can be established. In order to allow for effective mass transport between the different liquid phases involved, hollow fiber... 

Fig. 5-12. Separation of d,1-leucine in hollow-fiber membrane extraction using a Al- -dodecyl-l-hydrox-yproline solution in octanol as the enantioselective extraction liquid. The modules used were 32 cm long and contained 96 Celgard X-20 polypropylene fibers [57].

Figure 1 (left) Single extraction stage main equilibria between enantiomers R and S and enantioselective extractant C (right) fractional extraction scheme with wash stream (Kr > Ks). 

Easy protonation of tinchona alkaloids (ionic character) together with the possibility of modification of their lipophilicity makes this class of compounds interesting candidates for the enantioselective extraction. A pioneering work in this... 

Pickering, P. J., Chaudhuri, J. B. (1997). Enantioselective extraction of (D)-phenylalanine from racemic (D/L)-phenylalanine using chiral emulsion liquid membranes. Journal of Membrane Technology 127 115-130. 

The steroid-based scaffold was also used by Davis and coworkers to effect the enantioselective extraction of N-acyl a-amino acids from aqueous media. " Synthetic manipulation of cholic acid delivers a family of steroid-type derivatives (4) with different binding units at C3, Cl. and C12, which are predisposed to facilitate binding. A guanidinium group embedded in a six-membered ring was incorporated at C3 to enhance lipophilicity of the receptor. Variations in the asymmetry of the receptors using a variety of phenyl substituents permitted the researchers to tune the receptor for extraction of different amino acids. 

While the aforementioned ionophores are microbial metabolites, the crown polyethers, the depicted prototype of which is dicyclohexyl-18-crown-6 (Fig. 2D) are synthetic macrocyclic ethers. The first crown ether synthesized, dibenzo-18-crown-6, is the first multidentate synthetic macrocycle with the ability to form stable complexes with alkali and alkaline earth compounds. The complexing abilities of this crown ether led to the preparation of many others in rapid succession. Different size crown rings have been synthesized containing benzyl, cyclohexyl and naphthyl moieties Optically pure dinaphthyl crown ethers have been used to resolve asymmetric amine salts by enantioselective extraction from an aqueous solution into chloroform... 

Table 4. Enantioselective extractions by 13 and 14 of racemic A -acetyl a-amino acids from aqueous buffer (pH 7.4) into CHCI3.

I.2.I.4. Enantioselective Extractions Enantioselective iiquid-iiquid extraction (ELLE) is an implementation of the extraction of one enantiomer from a racemic mixture by the transfer between two liquid phases. Liquid-liquid extraction can be easily operated in a continuous counter-current mode to fractionate the racemate into its enantiomers, and this is a great advantage for the up-scaling. The possibility to operate at all scales, from laboratory separations to bulk processes in the chemical and pharmaceutical industries, makes this technology of a great interest to a... 

Steensma M, Kuipers NJM, De Haan AB, Kwant G. Identification of enantioselective extractants for chiral separation of amines and aminoalcohols. Chirality 2006 18(5) 314-328. 

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