Chiral resolution by crystallization of host-guest supramolecular complexes

Chiral Resolution through Precipitation of Diastereomeric Capsules in the Form of 2:1 β-Cyclodextrin−Guest Complexes

“…Linear correlation lines (r 2 > 0.99, Figure 3b) were obtained at two different wavelengths (DBO absorption at 370 nm and camphanate absorption at 228 nm), which allowed a determination of the ee in the obtained precipitate as 30 ( 3%. While moderate, this value is actually comparable to the optical purity achieved in preparative crystal growth experiments with modified CDs 13,14 and larger than the ee achieved in the original precipitation experiments by Cramer and Dietsche, which were conducted in the presence of a large excess of guest. 7 More importantly, the experimental enantiomeric ratio (2:1) is in excellent agreement with that expected (see above) from the ratio of the apparent equilibrium constants (K 1 K 2 values in Table 1).…”

“…Since CD-assisted stereodifferentiation in the solid state from racemate solutions has proven to be difficult for natural CDs, alternative methods have involved synthetic (per)methylated CDs, which are generally considered to be better host molecules for chiral discrimination purposes than natural CDs due to their higher flexibility. − Nevertheless, even with the structurally modified CDs, the achieved ee in the precipitates was found to be less than 30%, unless repeated precipitation of enantiomerically enriched fractions was pursued, , or unless the guest was selected to be in a racemization equilibrium, , which presents an impressive yet very special case. In some cases, the enantioseparation relied on differential crystal growth kinetics rather than on intrinsic solubility differences, which further limits routine use.…”

“…[11][12][13][14] Nevertheless, even with the structurally modified CDs, the achieved ee in the precipitates was found to be less than 30%, unless repeated precipitation of enantiomerically enriched fractions was pursued, 13,14 or unless the guest was selected to be in a racemization equilibrium, 11,12 which presents an impressive yet very special case. In some cases, the enantioseparation relied on differential crystal growth kinetics 15 rather than on intrinsic solubility differences, 14 which further limits routine use.…”

Racemic drug resolution: a comprehensive guide

“…Recently, some publications have shown the supramolecular interaction between host-guest complexes. [123][124][125][126] Novák et al and aerwards Ujj et al [127][128][129] resolved 1-alkyl, 1-aryl, and 1-alkoxy derivative of 3-methyl-3-phospholene-1-oxides by molecular complex formation with TADDOL derivatives. Novák et al 127,128 reported the rst enantiomeric separation of a cyclic phosphine oxide or a phosphinate by inclusion complex formation using TADDOL as a resolving agent.…”

Hydrophobic `lock and key' recognition of N-4-nitrobenzoylamino acid by strychnine

“…Although the diastereomeric salt method remains the most important method for the preparation of enantiopure compounds, up to now, the mechanism of chiral discrimination prevalent during crystallization of the diastereomers has not been clarified fully owing to the high complexity of the process (Kinbara et al, 1998(Kinbara et al, , 2000(Kinbara et al, , 2001Kozsda-Kovacs et al, 2000;Kano, 1997;Kato et al, 2003;Grandeury et al, 2004). In a recent paper, we concluded that in molecular recognition the donor/acceptor properties of a resolved compound can determine the self-assembly of the resolving agent, and the donor/acceptor capabilities of its surface correspond to the donor/acceptor properties of the resolved compound (Białoń ska & Ciunik, 2004).…”