Page 49 - 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)
2 Method Development and Optimization

of Enantiomeric Separations Using

Macrocyclic Glycopeptide Chiral
Stationary Phases

Thomas E. Beesley, J. T. Lee and Andy X. Wang

2.1 Introduction

Enantiomeric separations have become increasingly important, especially in the
pharmaceutical and agricultural industries as optical isomers often possess different
biological properties. The analysis and preparation of a pure enantiomer usually
involves its resolution from the antipode. Among all the chiral separation techniques,
HPLC has proven to be the most convenient, reproducible and widely applicable
method. Most of the HPLC methods employ a chiral selector as the chiral stationary
phase (CSP).
Currently, several hundred CSPs have appeared in publications, and over 110 of
them are available commercially [1]. These CSPs are made by using either a poly-
meric structure or a small ligand (MW < 3000) as the chiral selector. The polymeric
CSPs include synthetic chiral polymers [2] and naturally occurring chiral polymers
[3–5]. The most commonly used natural polymers include proteins and carbohy-
drates (cellulose and amylose). The chiral recognition mechanisms for these poly-
meric CSPs are relatively complicated. A protein, for example, is often complex
enough to contain several chiral binding sites, in which case the major (high-affin-
ity) site may differ for any given pair of enantiomers [6]. The other type of CSPs,
with a small molecule as the chiral selector, include ligand exchange CSPs [7],
π–complex (Pirkle-type) CSPs [8, 9], crown ether CSPs [10], cyclodextrin CSPs
[11–15] and macrocyclic glycopeptide CSPs [16–19]. Compared to the polymeric
CSPs, the separation mechanisms on these CSPs are better characterized and under-
stood. Macrocyclic glycopeptides, which were introduced by Armstrong in 1994
[16], are the newest class of CSPs. Three macrocyclic glycopeptides – vancomycin,
teicoplanin and ristocetin A – are now available commercially [20]. Much research
effort has been made on the characterization and application of these CSPs, and on
a wide variety of chiral compounds.