Targeted Selector Design

The classical PirMe-type phases are the most stable chiral stationary phases. They are mainly operated in normal phase mode and can be used to their fidl extent with SCCO2 (Macaudiere, 1986 Kraml, 2005). As the chiral selector is rather small and synthetically available, chiral phases with both enantiomers of the selector are often 

A special subclass of brush-type chiral stationary phases are the ion-exchange CSPs developed by Lammerhofer and Lindner (1996). By introducing an additional ionic moiety, a strong interaction between the selector and the selectand can be achieved. The first commercial available phases are based on the Cinchona alkaloids Quinine and Quinidine with an additional weak anion-exchange function offering good separation possibilities for chiral acids. A strong dependence of the capacity from the counter ion of the mobile phase could be demonstrated by Arnell (2009). 

In a complementary approach, chiral cation exchangers as well as 2witterionic phases have been developed but not yet commercialized. The good separation properties for a chiral amine with only small sidegroups next to the chiral center (R1 = -H, R2 = -CH3) has been recently published by Merck (Helmreich et al, 2010). By screening different selectors in a reciprocal approach an optimized chiral stationary phase could be developed to separate a molecule that has so far not been separated by all other known and commercially available chiral phases. 

It has to be once again stressed that it is not always the best choice to separate the final chiral molecule. By screening intermediates as well as easy obtainable derivatives, a dramatically better productivity might be achieved. A better solubility of the feed can especially lead to a much higher overall process performance. The approach of derivative screening is shown in more detail in Strube (2006). 

As a summary. Table 3.13 lists the features of the main groups of commercially available chiral stationary phases used for preparative chromatography. 

---

Figure 3.15 Rational screening process for enantioseparation by applying targeted selector design.

The quest for chiral selectors can be arbitrarily separated in two paths the synthetic route and the natural route. The synthetic route studies the chiral molecule evaluating possible interactions (Table 1) and designs a selector that will interact differently with an enantiomeric form than with its mirror image. The natural route follows Pasteur and uses the fact that the living world is made of countless chiral selectors and produces pure enantiomers. Once a natural chiral selector has been selected, it is tested with its natural chiral target(s) and with many other enantiomers. The observation of the results allows estimating a posteriori possible chiral mechanisms. 

---