Substituents chiral recognition studies

Fig. 5.20. Chiral crown ethers which have been used for chiral recognition studies with the ammonium ions in the inset. As a reference, the non-chiral crown at the center left was used. Bottom Three-point model for chiral recognition of ammonium ions in crown ethers (I = large, m = medium, s = small substituents).

Optical resolution of selenoxides by complexation is more efficient than that of sulfoxides. Although efficiency of the resolution for o- and />-tolyl-substituted sulfo- xides is not good, the efficiency for selenoxides with the same substituent is good. In order to clarify the mechanism of the efficient chiral recognition, X-ray crystal structure of a 1 1 complex of 14b and (-)-126f was studied.52... 

NMR. No similar catalysis was observed for a,p-unsaturated esters due to the s-cis conformation of the ester. In a later study, analogs of 47 with aromatic substituents on the bicyclic guanidinium were synthesized. These compounds were shown to increase catalysis, but no chiral recognition was observed [80]. 

Pioneering studies by Cram and co-workers employed crown ether arrays 35a-c incorporating a 2,2 -dihydroxy-l,l -binaphthyl unit as the chiral barrier <1975PAC327>. Enhancements in the chiral recognition of amino acids were obtained by placing large substituents, at the 3,3 -positions of the binaphthyl moiety, so as to raise its steric barrier. 3,3 -Diphenyl derivative 35c is often the benchmark to which other chiral crown ethers are compared <1981JOC393>. 

The enantiomeric separation of some racemic antihistamines and antimalar-ials, namely (+/-)-pheniramine, (+/-)-bromopheniramine, (+/-)-chlorophen-iramine, (+/-)-doxylamine, and (+/-)-chloroquine, were investigated by capillary zone electrophoresis (CZE). The enantiomeric separation of these five compounds was obtained by addition of 7 mM or 1 % (w/v) of sulfated P-cyclo-dextrin to the buffer as a chiral selector. It was found that the type of substituent and degree of substitution on the rim of the cyclodextrin structure played a very important part in enhancing chiral recognition (174). The use of sulfated P-cyclo-dextrin mixtures as chiral additives was evaluated for the chiral resolution of neutral, cyclic, and bicyclic monoterpenes. While there was no resolution of the monoterpene enantiomers with the sulfated P-cyclodextrin, the addition of a-cyclodextrin resulted in mobility differences for the terpenoid enantiomers. Resolution factors of 4-25 were observed. The role of both a-cyclodextrin and sulfated P-cyclodextrin in these separations was discussed (187). The enantiomeric separation of 56 compounds of pharmaceutical interest, including anesthetics, antiarrhythmics, antidepressants, anticonvulsants, antihistamines, antimalarials, relaxants, and broncodilators, was studied. The separations were obtained at pH 3.8 with the anode at the detector end of the capillary. Most of the 40 successfully resolved enantiomers contained a basic functionality and a stereogenic carbon (173). 

One of the interesting questions of CyD chemistry is whether inclusion complex-ation represents a prerequisite for chiral recognition and, if not, which part of the CyD, external or internal, provides a more favorable environment for enantioselec-tive recognition The synthesis of highly crowded heptakis-(2-0-methyl-3,6-di-0-sulfo)-j8-CyD (HMdiSu-jg-CyD) with 14 bulky sulfate substituents on both primary and secondary CyD rims can provide insights to this problem [62] since the bulky substituents on both sides of the cavity entrance may hinder inclusion complex formation between chiral analytes and HMdiSu-yS-CyD. In one study, 27 cationic chiral analytes were resolved in CE using native f-CyD and HMdiSu-yS-CyD [63]. For 12 of 16 chiral analytes resolved with both chiral selectors the enantiomer migration order was opposite. Analysis of the structures of analyte-CyD complexes in solution indicated that in contrast to mainly inclusion-type complexation between chiral analytes and j8-CyD, external complexes are formed between the chiral analytes and HMdiSu-j8-CyD [63]. 

Several studies demonstrated that the chiral recognition mechanism of CTB was based on the formation of inclusion complexes and, simultaneously, of hydrogen bonds between alcoholic hydrogen of the analyte and the carbonyl group of the CTB [33]. The type and shape of substituents attached to the stereogenic center strongly affected the permeability of the enantiomers into chiral cavities and, therefore, resolution. 

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