Recognition enantioselective

Within this approach, clathrates (for a definition see Chapter 1 in Vol. 140 of this series) and related lattice-type aggregates may be considered as multi-supramolecular systems where guest molecules are included in a crystal matrix. They allow a great many applications which have been specified in Vol. 140, first of all the separation of enantiomers by enantioselective recognition and inclusion of racemic guest molecules. 

Xu MH, Lin J, Hu QS et al (2002) Fluorescent sensors for the enantioselective recognition of mandelic acid signal amplification by dendritic branching. J Am Chem Soc 124 ... 

Chiral separation of drng molecules and of their precursors, in the case of synthesis of enantiomerically pure drugs, is one of the important application areas of HPLC in pharmaceutical analysis. Besides HPLC, capillary electrophoresis (CE) is another technique of choice for chiral separations. Chapter 18 provides an overview of the different modes (e.g., direct and indirect ones) of obtaining a chiral separation in HPLC and CE. The direct approaches, i.e., those where the compound of interest is not derivatized prior to separation, are discussed in more detail since they are cnrrently the most frequently used techniques. These approaches require the use of the so-called chiral selectors to enable enantioselective recognition and enantiomeric separation. Many different molecnles have been nsed as chiral selectors, both in HPLC and CE. They can be classified into three different groups, based on their... 

Gagne and coworkers utilized this combination to discover enantioselec-tive receptors for (-)-adenosine [12]. A racemic dipeptide hydrazone [( )-pro-aib] generated a stereochemically diverse DCL of n-mer. The dimers were composed of two chiral (DD/LL) and one achiral isomer (DL), the four trimers (DDD, LLL, DDL, and LLD), the tetramers of four chiral and two achiral isomers, etc. Two techniques were used to measure the enan-tio-imbalance that was caused by the enantioselective binding of the chiral analyte to the enantiomeric receptors (Fig. 5.11). Since the unperturbed library is optically inactive, the optical enrichment of each library component could be measured by a combined HPLC optical rotation detection scheme (laser polarimeter, LP). LP detection differentiated unselective binding (amplification but not optical enrichment) from enantioselective recognition of the analyte (amplification and optical enrichment). In this manner the LL dimer (SS) of the dipeptide was amplified and identified as the enantioselective match for (-)-adenosine. 

Galan A, Lu GY, Sanchez J, Seel C, de Mendoza J unpublished results A review involving enantioselective recognition Webb TH, Wilcox CS Chem Soc Rev 1993 383... 

A new type of chiral helical titanium reagent has been designed based on Ti(OPr )4 and a chiral ligand derived from enantiopure binaphthol. These Ti reagents have been successfully utilized as efficient chiral templates for the conformational fixation of u,fi-unsaturated aldehydes, thereby allowing excellent enantioselective recognition of the substrates to achieve... 

The prototype of a first fluorescence sensor for enantioselective recognition of chiral amino alcohols was synthesised by Pu et al. by linking phenylacetylene dendrons to an axially chiral binaphthol core unit (see Fig. 4.71) [14c, d, 25],... 

When complexation was carried out in MeOH, a 1 1 1 complex of the host, (—)-37 and MeOH was formed. Distillation in vacuo gave (—)-37 in 42% ee and 44% yield. In the case of complexes formed by the host 28, the large hydrophobic void space can competitively include a disordered toluene molecule or (—)-cyanohydrin [48], (S,S)-(—)-6, which in the solid state forms much smaller hydrophobic cavities, could not resolve rac-36 in either solvent. Under the same conditions, however, it successfully resolved rac 3-acetylcyclohex-2-enol, 38, forming 1 2 complexes in both solvents. From these (+)-38 was obtained in 40 % ee and 86 % yield, and 66 % ee and 79 % yield, respectively, from toluene and MeOH solutions. The above cases suggest that each of the hosts (28, 34 and 35) contains two recognition sites-one enantioselective, located around sterically hindered OH groups, and the other nonspecific, and located in the hydrophobic cavity. If molecules of one enantiomer and a solvent compete for the enantioselective recognition site (with H-bond formation), the enantioselectivity of the host... 

Cyclodextrin 6-O-monophosphates in both charged and uncharged forms have also been tested for enantioselective recognition of amino acids [23]. The best results were obtained for mono-(6-0-diphenoxyphosphoryl)- 3-cyclodex-trin, giving fairly good enantioselectivity of up to 3.6 for D/L-serine in buffered (pH=7.2) aqueous solution. 

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. 

We have prepared a very simple binaphthalene-based receptor 44 capable of enantioselective recognition of lactate and mandelate [74]. This extremely... 

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

Enantioselective metal chelation is a technique that has been applied to the separation of amino acid enantiomers. In the method, a transition metal-amino acid complex, such as copper(II)-aspartame, in which the full coordination of the complex has not been reached, is added to the buffer. The amino acid enantiomers are able to form ternary diastereomeric complexes with the metal-amino acid additive if there are differences in stability between the two complexes, enantioselective recognition can be achieved. 

M. Sawada et al., Cross-chiral examinations of molecular enantioselective recognition by fast atom bombardment mass spectrometry Host-guest complexations between chiral crown ethers and chiral organic ammonium ions. Org. Mass Spectrom. 28, 1525-1528 (1993)... 

Chirality is a pervasive property of an object, which means that in theory, a single remote asymmetric center in a macromolecule is enough to make the entire molecule chiral and, in principle, even the more distant residue could sense the asymmetry induced by the stereogenic center. On the contrary, experiences maturated by synthetic chemists in the construction of molecular species for enantioselective recognition speak for the necessity of placing the asymmetric units in close contact to allow chiral sensing and discrimination. The latter, in fact, arises from attractive forces and steric interactions that require close contact between the counterparts. On the contrary, magnetic asymmetry is not a direct consequence of weak interactions, but is more a property of the space which surrounds a chiral object. 

Other ee assays have been described, although in several cases the actual degree of throughput was not specified [10]. These systems include assays based on color tests [8,46 - 48,60], IR-thermography [49,61], circular dichroism [62], fluorescence [63], and even special forms of gas chromatography [64], Moreover, optically active compounds capable of enantioselective recognition of chiral substrates can be used as... 

Guanidines have been implemented early as recognition elements, guided by the apparent function of arginine in protein structures. The C2-symmetric, chiral anion receptor 52 was introduced by Lehn, Schmidtchen and de Mendoza consecutively and studied in various modifications (Scheme 13) [23c]. For example, an elaborate system based on 52 provided reasonable enantioselective recognition of amino acids [23c, 28]. Furthermore, bis(guanidinium) compounds catalyze RNA hydrolysis in the presence of external base via phosphodiester complexation [29]. The,se functional elements were joined in receptor 53 to yield a functional transesterification catalyst [30]. 

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