Page 173 - Chiral Separation Techniques

Chiral Separation Techniques: A Practical Approach, Second, completely revised and updated edition
Edited by G. Subramanian
Copyright © 2001 Wiley-VCH Verlag GmbH
ISBNs: 3-527-29875-4 (Hardcover); 3-527-60036-1 (Electronic)
6 Enantiomer Separations using Designed

Imprinted Chiral Phases

Börje Sellergren

6.1 Introduction

The need for efficient high-throughput techniques in the production of enantiomeri-
cally pure compounds is growing in parallel to the increasing structural complexity
of new drug compounds [1].
In the absence of synthetic methods allowing the drug to be synthesized in opti-
cally pure form, the resolution of racemates using characterized chiral selectors or
auxiliaries is the first step in this process. These techniques have the additional
advantage of providing both enantiomers in preparative amounts, which means that
the requirements for biological testing of both enantiomers can be met. Convention-
ally, preparative optical resolution is performed by fractional crystallization, micro-
biological methods, kinetic enzymatic resolution and by chromatography. Of
growing importance are methods allowing continuous production of pure enan-
tiomers. In chromatography, these can be based on liquid–solid partitioning as in
simulated moving bed (SMB) chromatography (see Chapter 10) or liquid–liquid par-
titioning as in countercurrent distribution [2, 3] or chromatography [4]. In the case
of phases exhibiting particularly high enantioselectivities, batch- [5], membrane-,
[6–8] or bubble- based [9] separation techniques may be more attractive.
In chromatography, polysaccharide-based phases (modified amylose or cellulose)
are, due to their high site density and broad applicability, the most common phases
used for preparative-scale separations [10]. A problem with these, as well as other
common CSPs, is the limited predictability of elution orders and separability, mak-
ing screening of stationary phase libraries a necessary step in the method develop-
ment [10]. Polymers imprinted with chiral templates here promise to alleviate these
problems offering a new generation of custom-made CSPs with predictable selectiv-
ities [11]. In view of the high selectivity often exhibited by these phases, preparative
applications in the above-mentioned formats are being investigated. This review will
summarize the present state of this research field.