Page 86 - Chiral Separation Techniques

62 3 Combinatorial Approaches to Recognition of Chirality: Preparation …

families of compounds [52–55] The reciprocal method is particularly suitable for sit-
uations in which the target enantiomer is known and its separation from a racemate
is required. Since chromatographic techniques are readily automated, a broad vari-
ety of novel chiral ligands may be considered.

3.5.2 Combinatorial Chemistry

Although the reciprocal approach potentially enables the screening of large numbers
of compounds, only the advent of combinatorial chemistry brought about the tools
required for the synthesis of large libraries of potential selectors in a very short
period of time. In addition, using the methods of combinatorial chemistry, novel
strategies different from those of the reciprocal approach could also be developed.
Combinatorial chemistry and high-throughput parallel synthesis are powerful
tools for the rapid preparation of large numbers of different compounds with numer-
ous applications in the development of new drugs and drug candidates [56–58],
metal-complexing ligands and catalysts [59–63], polymers [64], materials for elec-
tronics [65, 66], sensors [67], supramolecular assemblies [68–70], and peptidic li-
gands for affinity chromatography [71]. The essence of combinatorial synthesis is
the ability to generate and screen or assay a large number of chemical compounds –
a “library” – very quickly. Such an approach provides the diversity needed for the
discovery of lead compounds and, in addition, allows their prompt optimization. The
fundamentals of combinatorial chemistry, including rapid screening methodologies,
are reviewed in numerous papers and books [72, 73]. The following sections of this
chapter will describe a variety of different combinatorial methods that have led to
selectors for the recognition of chirality aiming mainly at the development of robust
media for the separation of enantiomers.

3.6 Library of Cyclic Oligopeptides as Additives to Back-
ground Electrolyte for Chiral Capillary Electrophoresis

Enantioresolution in capillary electrophoresis (CE) is typically achieved with the
help of chiral additives dissolved in the background electrolyte. A number of low as
well as high molecular weight compounds such as proteins, antibiotics, crown
ethers, and cyclodextrins have already been tested and optimized. Since the mecha-
nism of retention and resolution remains ambiguous, the selection of an additive best
suited for the specific separation relies on the one-at-a-time testing of each individ-
ual compound, a tedious process at best. Obviously, the use of a mixed library of chi-
ral additives combined with an efficient deconvolution strategy has the potential to
accelerate this selection.