Page 114 - Chiral Separation Techniques

90 3 Combinatorial Approaches to Recognition of Chirality: Preparation …

In contrast, there are fewer limitations from the chemical point of view. The
preparation of large, well-defined, libraries that involve amino acid building blocks
has been demonstrated many times. Carefully optimized reaction conditions for the
preparation of other mixed libraries can also ensure that each desired compound is
present in sufficient amount. However, the reaction rates of some individual selec-
tors with the activated solid support may be lower than that of others. As a result, the
more reactive selectors would occupy a majority of the sites within the beads. Since
the most reactive selectors may not be the most selective, testing of a slightly larger
number of specifically designed CSPs may be required to reduce the effect of false-
negative results.
While the reciprocal approach is best suited for the development of a CSP for a
single, well-known racemic target, the library-on-bead technique is more useful for
the initial scanning of various targets to find a lead selector. It is easy to imagine a
development laboratory with a number of columns with immobilized libraries of
selectors used to screen target racemates in very rapid fashion. Such pre-screening
would suggest the type of selector chemistry that may be best suited for a specific
target. The next step would either involve deconvolution of the library on bead or
reciprocal testing of parallel libraries of selectors with analogous core chemistries.

3.8 Conclusion

Combinatorial chemistry, a powerful tool in many areas such as drug discovery,
materials research, and catalysis, can also be used effectively in the area of molecu-
lar recognition to discover new selectors for the recognition of chirality. To date,
only a few combinatorial strategies leading to chiral selectors have been demon-
strated in the literature. Other approaches such as combinatorial molecular imprint-
ing [96–98] may soon emerge to expand the scope of combinatorial recognition pro-
cesses. In the future, it is very likely that combinatorial methods will become a
widely used tool, even for the development of effective selectors for specific targets.
The power of combinatorial chemistry resides in both the large numbers of com-
pounds that can be prepared within a very short period of time and the rapid assay
and deconvolution techniques that may be used for testing to discover the optimal or
near-optimal selector within the library. This availability of libraries encompassing
a broad diversity of ligand types enables rapid identification of suitable selector fam-
ilies, their comparative screening, and the rapid preparation of custom-made separa-
tion media for the resolution of specific racemates [99]. As an additional benefit,
studies carried out with broad arrays of structurally related families of selectors can
further improve the general understanding of chiral recognition.
Chiral separation media are quite complex systems. Therefore, neither combina-
torial methods nor even the identification of the best selector can ensure that an out-
standing chiral separation medium will be prepared. This is because some other vari-
ables of the system such as the support, spacer, and the chemistry used for their con-