Page 40 - Chiral Separation Techniques

1.5 Other Methods 15

ditions. Chiral crown ethers [171–173], cyclodextrins [174] and amino acid deriva-
tives [19–22] have been successfully used in the resolution of free amino acids
[175–178], amino acid derivatives [175], cyclic and heterocyclic compounds [174]
and also racemic drugs, such as the β-blockers propranolol and bupranolol [177].
Another possibility of constructing a chiral membrane system is to prepare a solu-
tion of the chiral selector which is retained between two porous membranes, acting
as an enantioselective liquid carrier for the transport of one of the enantiomers from
the feed solution of the racemate to the receiving side (Fig. 1-5). This system is often
referred to as membrane-assisted separation. The selector should not be soluble in
the solvent used for the elution of the enantiomers, whose transport is driven by a
gradient in concentration or pH between the feed and receiving phases. As a draw-
back common to all these systems, it should be mentioned that the transport of one
enantiomer usually decreases when the enantiomer ratio in the permeate diminishes.
Nevertheless, this can be overcome by designing a system where two opposite selec-
tors are used to transport the two enantiomers of a racemic solution simultaneously,
as it was already applied in W-tube experiments [171].
Most of the chiral membrane-assisted applications can be considered as a modal-
ity of liquid–liquid extraction, and will be discussed in the next section. However, it
is worth mentioning here a device developed by Keurentjes et al., in which two mis-
cible chiral liquids with opposing enantiomers of the chiral selector flow counter-
currently through a column, separated by a nonmiscible liquid membrane [179]. In
this case the selector molecules are located out of the liquid membrane and both
enantiomers are needed. The system allows recovery of the two enantiomers of the
racemic mixture to be separated. Thus, using dihexyltartrate and poly(lactic acid),
the authors described the resolution of different drugs, such as norephedrine, salbu-
tamol, terbutaline, ibuprofen or propranolol.

1.5 Other Methods

1.5.1 Chiral Extractions

Liquid-liquid extraction is a basic process already applied as a large-scale method.
Usually, it does not require highly sophisticated devices, being very attractive for the
preparative-scale separation of enantiomers. In this case, a chiral selector must be
added to one of the liquid phases. This principle is common to some of the separa-
tion techniques described previously, such as CCC, CPC or supported-liquid mem-
branes. In all of these, partition of the enantiomers of a mixture takes place thanks
to their different affinity for the chiral additive in a given system of solvents.
The instrumentation which until now has been used in chiral extraction experi-
ments is very diverse, ranging from the simple extraction funnel [123, 180], the U-
or W-tubes [171, 181], to more sophisticated devices, such as hollow-fiber extraction
apparatus [175] or other membrane-assisted systems. Most of these experiments