Polysaccharides, chiral recognition

Polysaccharide-based CSPs incorporate derivatives of cellulose and amylose adsorbed on silica gel. The selectivity of these CSPs depends upon the nature of the substituents introduced during the derivatization process. The secondary structure of the modified polysaccharide is believed to play a role in selectivity, but the chiral recognition mechanisms have not been fully elucidated [55]. 

Polysaccharide analogue, polyether 15, prepared through anionic cyclopolymerization, was chemically bonded to silica gel.73 The CSP resolved several a-amino acids the chiral recognition abilities of the analogue of 15 have been evaluated.74... 

As previously mentioned above, the chiral recognition abilities of the phenyl-carbamates of polysaccharides are greatly influenced by the substituents on the phenyl groups. In order to evaluate the effect of the substituents on the interaction between CSPs and solutes, the retention times of acetone and the first-eluted isomer of l-(9-anthryl)-2,2,2-trifluoroethanol (39) on 3- and 4-substituted CSPs are plotted against the Hammett parameter a of the substituents (Figure 3.33).130 The retention times of acetone tend to increase as the electron-withdrawing power of the substituents increases, whereas those of the first-eluted isomer of 39 tend to decrease. These results indicate that... 

Among optically active polymers, polysaccharide derivatives are particularly valuable. Polysaccharides such as cellulose and amylose are the most readily available optically active polymers and have stereoregular sequences. Although the chiral recognition abilities of native polysaccharides are not remarkable, they can be readily converted to the esters and carbamates with high chiral recognition abilities. The chiral recognition mechanism of these derivatives has been clarified to some extent. 

Most screening and optimization approaches in HPLC were defined using polysaccharide chiral stationary phases (CSP), thanks to their broad chiral recognition ability toward a large number of compounds. 

Different classifications for the chiral CSPs have been described. They are based on the chemical structure of the chiral selectors and on the chiral recognition mechanism involved. In this chapter we will use a classification based mainly on the chemical structure of the selectors. The selectors are classified in three groups (i) CSPs with low-molecular-weight selectors, such as Pirkle type CSPs, ionic and ligand exchange CSPs, (ii) CSPs with macrocyclic selectors, such as CDs, crown-ethers and macrocyclic antibiotics, and (iii) CSPs with macromolecular selectors, such as polysaccharides, synthetic polymers, molecular imprinted polymers and proteins. These different types of CSPs, frequently used for the analysis of chiral pharmaceuticals, are discussed in more detail later. 

Chiral resolution on polysaccharide-based CSPs is due to the different types of bonding between racemates and CSP, as discussed later in this chapter. Therefore, different racemate structures provide bondings of different types, which in turn means that different patterns of chiral recognition will be observed. The effects of... 

Yashima E, Okamoto Y, Chiral recognition mechanism of polysaccharides chiral stationary phase in The Impact of Stereochemistry on Drugs Development and Use (Aboul-Enein, HY, Wainer IW, Eds.), John Wiley Sons, New York, p. 345 (1997). 

The chiral recognition mechanisms in NLC and NCE devices are similar to conventional liquid chromatography and capillary electrophoresis with chiral mobile phase additives. It is important to note here that, to date, no chiral stationary phase has been developed in microfluidic devices. As discussed above polysaccharides, cyclodextrins, macrocyclic glycopeptide antibiotics, proteins, crown ethers, ligand exchangers, and Pirkle s type molecules are the most commonly used chiral selectors. These compounds... 

Polysaccharide-based CSPs also exhibit a chiral recognition for alcohols and a large number of resolutions have been reported. Chiral alcohols can usually be directly resolved with hexane containing a small amount of an alcohol as the eluent. For aliphatic alcohols, which cannot be directly resolved, their resolution is often efficiently attained as phenylcarbamate or benzoate derivatives on OD (Figure 17).85 For example, 2-butanol and 2-pentanol are completely resolved with a very high selectivity on OD as their phenylcarbamates. The derivatization of alcohols to phenylcarbamates and benzoates can be easily achieved by the reaction with phenyl isocyanates and benzoyl chlorides, respectively. In most cases, the phenylcarbamates are better resolved than the benzoates. For chiral compounds bearing phenolic hydroxy groups, the addition of a small amount of an acid to an eluent is recommended to depress its dissociation. 

Chiral separation by HPLC is a practically useful method not only for determining optical purity but also for obtaining optical isomers, and numerous CSPs are presently on the market. In order to achieve the efficient resolution of chiral compounds, we have to choose a suitable chiral column and eluent. The polysaccharide-based CSPs have a high chiral recognition ability and offer a high possibility for the successful resolution of racemates including aliphatic and aromatic compounds with or without functional groups under normal and reversed-phase conditions. 

The chiral recognition mechanism of polysaccharide derivatives at a molecular level has been solved to some extent by chromatography, NMR, and computational methods.89 93 This will be helpful in selecting suitable resolution conditions and in developing more effective CSPs. 

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