Chiral cavities

It is well recognized that chiral tridentate ligands generally form a deeper chiral cavity around the metal center than a bidentate ligand. For example, as mentioned in previous chapters, the chiral tridentate ligand Pybox 120 has been used in asymmetric aldol reactions (see Section 3.4.3) and asymmetric Diels-Alder reactions (see Section 5.7). The two substituents on the oxazoline rings of 120 form a highly enantioselective chiral environment that can effectively differentiate the prochiral faces of many substrates. 

In this case, the material s specific chiral cavities are created by utilizing phenyltrimethoxysilane and TMOS as the monomers and the chiral cationic surfactant A-dodecyl-TV-methylephedirnium (DMB) as template,... 

In complexes of crown ethers [303] to [305] (types IV and V) both large groups are located in the larger of the two non-equivalent chiral cavities (Kyba et al., 1978). This was concluded from H nmr spectra of the diastereomeric complexes of [303] with a-phenylethylammonium salts. In the spectra the position of the methyl protons in both diastereomeric complexes is the same, in contrast to the methyl protons in complexes of [284] or [285] with the same salt. In the latter the upheld shift of the methyl protons in the more stable SS-(R) enantiomeric complex differs from that in the less stable SS-(S) enantiomer. Taking into account the available data summarized above, the tentative conclusion seems to be that the simple steric model (see structure... 

MD simuations on low-energy [9-H-A] (A = alanine) docking geometries point to EXT as the thermodynamically most favored structures at room temperature. The relevant diastereomeric structures are almost equally stable. Therefore, the observed enantioselectivity has to be attributed to specific stabilization of the exhange transition structures. In this view, the small effects of the configuration of B Sb = (kfi/ks in Table 17) indicates that the B amine displaces alanine from the relevant EXT structure without getting completely into the chiral cavity of the host. 

The inclusion of enantiomers into the chiral cavities of the network is supposed to be the main chiral recognition mechanism. Moreover, hydrogen bonding between polar groups of the solutes and the amide groups of the polymers are also assumed to participate in the chiral recognition process. Apolar mobile phases such as hexane-dioxane and toluene-dioxane mixtures are therefore commonly used with this type of CSPs. 

Molecular imprinted polymers MIPs exhibit predetermined enan-tioselectivity for a specific chiral molecnle, which is nsed as the chiral template dnring the imprinting process. Most MIPs are obtained by copolymerization from a mixture consisting of a fnnctional mono-nnsatn-rated (vinylic, acrylic, methacrylic) monomer, a di- or tri-nnsatnrated cross-linker (vinylic, acrylic, methacrylic), a chiral template (print molecnle) and a porogenic solvent to create a three-dimensional network. When removing the print molecnle, chiral cavities are released within the polymer network. The MIP will memorize the steric and functional binding featnres of the template molecnle. Therefore, inclusion of the enantiomers into the asymmetric cavities of this network can be assumed as... 

At this point it is impossible to guess the architecture of the active catalyst. The folding of 10-mers of leucine and alanine in organic solvents is clearly of critical importance, and studies are in progress to understand the preferred shapes. Obviously, in its active form the catalyst binds and activates peroxide anion and/or the electron-poor alkene near its chiral surface, perhaps in a chiral cavity, but the precise orientation of catalyst and reactants in the initial bondforming Michael reaction remains unsolved. 

One or both of the disadvantages are Hkely to be overcome in due course. It is obvious that a clearer picture of the mechanism of the oxidation is mandatory before much progress can be made. Once it is understood how this very simple protein folds, in the presence of organic solvent, to form a chiral cavity or chiral surface that activates the peroxide and/or enone to accomplish the desired asymmetric oxidation then the reaction may be extended to other substrates, e.g. a, unsaturated esters, nitroalkenes, perhaps (under different conditions) electron-rich alkenes. 

Enantiomer separation on modified macrocyclic cyclodextrin phases via inclusion into chiral cavities. ... 

Wulff G, Grobe-Einsler R, Vesper W, Sarhan A. Enzyme-analog built polymers. 5. The specificity distribution of chiral cavities prepared in synthetic polymers. Makromol Chem... 

More recently alkylated cyclodextrins have been developed as chiral phases. These phases are based on cyclodextrins, which are cyclic structures formed from 6, 7 or 8 glucose units. Alkylation of the hydroxyl groups in the structure of the cyclodextrins lowers their melting points and makes them suitable as GC phases. The cyclodextrins contain many chiral centres and separate enantiomers of drugs according to how well they fit into the chiral cavities of the cyclodextrin units (see Ch. 12 p. 273). 

For example, cyclodextrins form chiral cavities which adsorb the corresponding enantiomers with different affinity while cellulose triacetate crystallizes in the form of helical substructures in which the enantiomers may be incorporated with different rates. For amino acid derived stationary phases there are two types of enantiomer differentiating interactions a brush-like hydrogen bond and dipole interaction plus a /[-complex donor or acceptor interaction with the aromatic residues in the amino acid. 

In addition to the classification of liquid chromatographic enantioseparation methods by technical description, these methods could further be classified according to the chemical structure of the diverse CSPs. The chiral selector moiety varies from large molecules, based on natural or synthetic polymers in which the chirality may be based on chiral subunits (monomers) or intrinsically on the total structure (e.g., helicity or chiral cavity), to low molecular weight molecules which are irreversibly and/or covalently bound to a rigid hard matrix, most often silica gel. 

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