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.

for NMR

for HPLC

for X-ray Crystallography

for Exciton Chirality CD Method

for NMR

A1657	A1658	B1720
B1721	B1143	B1144
B1161	B1343	C1021
C2184	D2459	D2460
D1852	D1853	D2175
D2176	M0661	M0662
M1366	M1367	M0829
M0830	M0831	M0832
M1339	M1103	M1104
I0334	I0335	N0713
N0714	N0481	N0482
I0336	I0398	P0793
P0794	P1219	P1220
S0473	S0474	T1520
T1521

for HPLC

A1657	A1658	A5560
A5561	A5564	A5565
A5568	A5569	D2259
A5523	A5524	M1366
M1367	I0334	I0335
N0713	N0714	I0336
I0398	A5562	A5563
A5566	A5567	A5577
A5578	A5514	A5515

for X-ray Crystallography

C1682	C1766	C1683
C1767

for Exciton Chirality CD Method

for Hydroxyl Groups

A0482	A0690	A1150
B0062	B0105	P0961
B0553	B0558	C0134
C0141	C0445	C1182
D0724	M0721	M1338
M0576	N0025	N0048
N0156	N0176	P1079

for Primary Amino Groups

D0645	D1495	D0648
N0530

for Monoalcohols, Monoamines

B3515	B2124	A1371
B1185	P1364