Enantioselective recognition carboxylates

The bicyclic receptors 40 and 41 were also prepared for enantioselective recognition of chiral carboxylates [69, 70]. The substitution of two benzene rings by pyridines in the receptor 41 enriched this molecule with two additional sites capable of hydrogen bond formation. 

Ligand 62 [83] was prepared for the enantioselective recognition of amino acids. Chiral carboxylates are bound by cooperative binding by electrostatic... 

Another interesting development is the use of bicyclic guanidinium receptors as heteroditopic systems for the enantioselective recognition of amino acids. In this case the guanidinium fragment was combined via a flexible linker with a crown ether moiety in order to promote the simultaneous binding of the carboxylate anion and the ammonium cation belonging to a zwitterionic amino acid [45]. 

Fig. 14. Urea molecules used for binding of carboxylates. Molecule 19 has additional hydrogen-bonding sites and 20 has chiral R groups for enantioselective recognition...

Recently, Lee and co-workers have shown that abinol-strapped calix[4]pyr-role (49) can be used in the enantioselective recognition of carboxylate anions [66]. Both the R- and S-enantiomers of the strapped calixpyrrole were isolated and characterized. Detailed studies of the enantioselectivity of the S enantiomer were carried out by isothermal titration calorimetry experiments in acetonitrile with the chiral anions (R)-2-phenylbutyrate and (S)-2-phenylbutyrate. Stability constants were determined and revealed... 

The design of 11 was aimed at the enantioselective recognition of zwitterionic aromatic amino acids under neutral conditions.The features of the receptor include a chiral structure, an aromatic substituent for n-stacking. and binding sites for a carboxylate group and an ammonium... 

Chen Z-H, He Y-B, Hu C-G et al (2008) Preparation of a metal-ligand fluorescent chemosensor and enantioselective recognition of carboxylate anions in aqueous solution. Tetrahedron Asymmetry 19 2051-2057... 

Boronic acid-derived fluorescent chemosensors are unique in that the inter-molecular interaction is a covalent bond, and not hydrogen bonding as is the case for most conventional fluorescent molecular sensors used for the selective reeognition of hydroxyl carboxylic acids. This chapter summarizes the development of the boronic acid-based chiral fluorescent chemosensors over recent years and the enantioselective fluorescent reeognition of chiral a-hydroxyl carboxylic acids analytes in aqueous solutions. The fundamental scaffolds of these chiral sensors include a fluorophore, an arylboronie aeid binding site, and linker between the two units. The systems usually consist of a bis-boronic acid unit, which is required for enantioselective recognition of the chiral a-hydroxyl carboxylic acid analytes. However, mono-boronic acid fluorescent chemosensors have also been developed. All three components of the chiral boronic acid sensors play an important role in determining the... 

In seeking to realise this notion, we chose carboxylates as substrates for two reasons. Firstly, we could avail of the well-known carboxylate-guanidinium recognition motif, as in 11, to establish and dominate complex formation.Secondly, the amphiphilic nature of carboxylates allowed us to aim for enantioselective phase transfer, an easy phenomenon to detect and potentially very useful for the large scale resolution of racemates. ... 

The dependence of chiral recognition on the formation of the diastereomeric complex imposes constraints on the proximity of the metal binding sites, usually either an hydroxy or an amine a to a carboxylic acid, in the analyte. Principal advantages of this technique include the ability to assign configuration in the absence of standards, enantioresolve nonaromatic analytes, use aqueous mobile phases, acquire a stationary phase with the opposite enantioselectivity, and predict the likelihood of successful chiral resolution for a given analyte based on a well-understood chiral recognition mechanism. 

Despite the relatively large number of enantioselective receptors of cations and neutral species, reports on the effective chiral recognition of anions are still rare. However, there are a number of reports in the literature describing the recognition of carboxylic acids, and amino acids in particular, performed in aqueous solution at a pH where the carboxylic group has to be at least partly ionized. These reports are also included in this review. 

The same author has reported chiral recognition of a-amino acids by native, anionic, and cationic a- and (3-cyclodextrins [17]. Both carboxylates and amines (monosubstituted as well as hexa- and heptasubstituted) were included in this study. The best results obtained were those from a combination of (S)- and (P)-AcTrp complexed by per-NH -[3-cyclodextrin with K=2,310 and 1,420 (1/mol). In the detailed study of chiral recognition of substituted phenyl-acetic acid derivatives by aminated cyclodextrins, these were found to be again only modest with respect to the enantioselection attained [18]. 

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