Cinchona Alkaloids as Chiral Solvating Shift Agents in NMR Spectroscopy

Cinchona Alkaloids as Chiral Solvating (Shift) Agents in NMR Spectroscopy 

Mechanistic studies on the interaction of quinine or quininyl-9-O-carbamates 69 and 70 with selected enantiomer pairs, employing sophisticated NMR experiments and molecular modeling, have been carried out by the Salvadori group. These studies revealed that due to the multifunctional character of the CSA molecules and their specific conformational preferences, each type of analyte induced its own specific interaction pattern [134, 137]. The main driving forces leading to enantiodiscrimination are due to hydrogen bonds between hydroxy group in QN or 

At the end of this section, we would like to mention that there are some limitations associated with the use of cinchona alkaloids as CSA. These include the possibility of self-association of alkaloids that has been observed, for example, with dihydroqui-nidine as early as in 1969 [138]. The rich and complex 1H NMR spectra of cinchona alkaloids can overlap with the sample absorption in the region of interest. Nevertheless, the simplicity of the CSA approach, low price of parent cinchona alkaloids, and numerous cinchona derivatives synthesized so far should stimulate further development of new target-specific applications in this field. 

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