Quinidines chiral selectors

Overall, the /er/-butyl carbamates of quinine and quinidine evolved as the most effective chiral selectors among this family because of their broad enantioselectivity spectmm and exceptional degree of selectivity for a wide variety of chiral acids. On... 

M. Lammerhofer and W. Lindner, Quinince and quinidine derivatives as chiral selectors. Beush type chiral stationary phases for high performance liquid chromatography based on chincona carbamates and their applications as chiral anion exchanger, J. Chromatogr. 741 (1966), 33. 

Recently, Lindner and coworkers developed a series of anion-exchange CSPs based on quinine and quinidine as chiral selectors (Fig. 6.11) [79, 80]. These phases are particularly appropriate for the separation of the enantiomers of chiral acidic compounds. Improvement of the chiral recognition power of these phases by rationally designed structural modifications has led to exceptionally high enantioselectivity which, of course, is of great interest for preparative applications [81]. Screen-... 

Quinine, quinidine and cinchonidine, which are amino alcohols with high chiral capability, have been used as selectors for the separation of enantiomers of acids containing a hydrogen bonding function [24]. These chiral selectors have high UV absorbance, providing indirect detection possibilities for solutes without inherent UV absorbance (Figure 6). 

FIGURE 9.5 Measurement and treatment of data for a host-guest screening experiment. The chiral selector, ferf-butylcarbamoyl quinidine (tBuCQD) is shown to provide a high degree of enantioselectivity toward the discrimination of enantiomers of N-(3,5)-dinitrobenzoyl-leucine (DNB-Leu) using ESI-MS [87]. 

Xiao TL, Armstrong DW (2004) Macrocyclic antibiotics. Chapter 4. In Giibitz G, Schmid MG (eds) Chiral separations, methods and protocols. Humana Press, Totowa, NJ, pp 113-171 Lammerhofer M, Lindner W (1996) Quinine and quinidine derivatives as chiral selectors. I. Brush type chiral stationary phases for high-performance Uquid chromatography based on cinchonan carbamates and their application as chiral anion exchangers. J Chromatogr A 741 33-48... 

Quinine (QN) and quinidine (QD) are natural enantiomers belonging to the cinchona alkaloid family, an important subgroup of naturally occurring polycyclic P-carboline alkaloids. They are widely used as resolving agents for chiral acids via preferentially forming diastereomerie salts with one of the enantiomers [117]. From the reciprocity concept point of view, the logic path is that QN and QD are potential chiral selectors... 

Lammerhofer M, Lindner W (1996) Quinine and quinidine derivatives as chiral selectors. 1. Brush type chiral stationary phases for HPLC based on dnchonan carbamates and their application as chiral anion exchangers. J Chromatogr A 741 33-48... 

The cinchona alkaloid-based stationary phases are chiral stationary phases where quinine/ quinidine are chemically bonded to a silica gel matrix. The interaction between the selectand and selector is based on charge transfer n-n interactions as well as ion pairing with the selector. They operate under aqueous-organic mobile phases or mixtures of organic solvents such as hexane-alcohols. 

Among the many carbamates screened, quinine and quinidine tert-butyl-9-O-carbamates (t-BuCQN and t-BuCQD) (Figure 13.12) were found as the most versatile and easy-to-get selectors. They were commercialized in the late 1990s, initially by Bischoff GmbH and then by Chiral Technologies [63]. 

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). 

Table 6 Logarithms of association constants and thermodynamic parameters (kJ mol selectors 7, 8, quinine, and quinidine in methanol at 25 °C. ) for binding of (T )-5, (5)-5, and 6 to the chiral ...

The two Cinchona alkaloid selectors will be used to really get into a particular chiral recognition mechanism. Quinine is a natural alkaloid extracted from the bark of the South American Cinchona tree of the Rubiaceae family and used as an anti malaria drug (Fig. 6). Its 8 and 9 positions are, respectively, substituted in the S and R configuration. By chance, quinidine is the mirror image form of quinine, also found in the Cinchona bark with the 8R and 9S configuration. These two alkaloid enantiomers... 

Fig. 6 Top the quinine and quinidine selectors. Bottom Chiral recognition mechanism by a quinine-based chiral stationary phase (CSP). The strongest interaction is the ionic docking attraction between charges of opposite signs. DNB-D-valine is more retained by the quinine CSP than its L-enantiomer. DNB-L-valine is more retained by the quinidine CSP. All three interactions occur between three different substituents of both the quinine selector and amino acid selectand. Compare with Fig. 5. Adapted from [41]...

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