Page 28 - Chiral Separation Techniques

1.3 Chromatographie Techniques 3

On that basis, crystallization is often used in combination with other enantiose-
lective techniques, such as enantioselective synthesis, enzymatic kinetic resolution
or simulated moving bed (SMB) chromatography [10, 11]. In general, when refer-
ring to crystallization techniques, the aim is to obtain an enantiomeric enrichment in
the crystallized solid. However, the possibility of producing an enrichment in the
mother liquors [12, 13], even if this is not a general phenomenon [14], must be taken
into account.
An additional strategy that is frequently used due to the reduced probability of the
preceding situations is the separation of diastereomeric mixtures obtained from the
reaction of the original enantiomeric mixture with chiral derivatizing agents [3,
15–18]. These should be easily cleaved from the target molecule with no racemiza-
tion, and thus be readily available. Low cost and confirmed enantiomeric purity, in
addition to their being recoverable and reusable, are also highly recommended prop-
erties for a chiral derivatizing agent.

1.3 Chromatographic Techniques

1.3.1 Liquid Chromatography

Despite the fact that in former days liquid chromatography was reputed to be a very
expensive and inefficient purification technique for preparative purposes, it is nowa-
days one of the first choices to carry out a large-scale chiral separation. On the one
hand, some technical developments, related to the equipment as well as to the pack-
ing materials have improved the efficiency of the technique. On the other hand,
applications such as the resolution of enantiomers, where the resulting products have
a high added value, can partially balance the classically attributed high costs of li-
quid chromatography. Furthermore, the relative short time necessary to develop a
chromatographic method, and the availability of chromatographic systems, are inter-
esting features that should be taken into account when the enantiomers under con-
sideration need to be separated in the minimum time.
Analogously to crystallization techniques, the chromatographic separation pro-
cess can be applied either to a mixture of enantiomers or to diasteromeric derivatives
obtained by reaction with chiral derivatizing agents. In this case, it is a conventional
chromatographic process which can be performed in achiral conditions, and the
same drawbacks as with any other indirect method might be encountered. Thus, such
indirect resolutions are strongly dependent on the enantiomeric purity of the deriva-
tizing agent which must be cleaved without affecting the configuration of the stereo-
genic elements in the target molecule.
Several chromatographic modes will be reviewed in this respect, and most will
make use of a chiral support in order to bring about a separation, differing only in
the technology employed. Only countercurrent chromatography is based on a li-
quid–liquid separation.