Most biologically active compounds including pharmaceuticals have chiral molecular structures with one or more stereogenic centers. The absolute configuration of pharmaceuticals is very important for biological activity. Generally one enantiomer has medicinal activity while the other enantiomer has no activity. In some cases the opposite enantiomer gives rise to adverse and harmful effects. For this reason it is of great significance to obtain enantiopure compounds and to develop chiral auxiliaries for the determination of their absolute configurations and enantiomeric excess. Various kinds of reagents have been developed to determine their absolute configurations and enantiomeric excess by NMR1), HPLC2) and CD exciton chirality method3). A chiral shift reagent, Chirabite-AR (1), developed by Ema et al. is also one of the such reagents, and the optical purity can be easily measured using NMR.4)
Chirabite-AR (1) is a macrocyclic compound and has a very unique cavity where the hydrogen-bond donor and acceptor sites are well organized to enable the binding of a wide range of compounds as guest molecules. The incorporated guest molecules experience a strong anisotropic ring-current effect arising from the BINOL moiety, which is a chiral source, resulting in the chemical-shift nonequivalence between the two enantiomers.
When conventional europium complexes are used on high-field NMR spectrometers, which are widely spread nowadays, signal broadening occurs, and as a result, satisfactory NMR spectra cannot be obtained. Because 1 contains no paramagnetic metals, which cause signal broadening, it can be used for both high- and low-field NMR spectrometers. Using 1, therefore, the enantiomeric purities of various compounds such as carboxylic acids, oxazolidinones, carbonates, lactones, alcohols, sulfoxides, sulfoximines, sulfinamides, isocyanates and epoxides can be determined. Moreover, a protocol for its determination is extremely easy; NMR spectra showing chemical-shift nonequivalences can be obtained just by adding 1 to the NMR tube containing a target sample in CDCl3.
The reagent 1 is characterized by its facile use, versatility, and applicability to the low- and high-field NMR spectrometers. Thus, 1 has been shown to possess a highly effective capacity superior to that of the conventional chiral shift reagents.