CyDs permethylated

On the basis of X-ray analysis, methylated or acetylated CyDs are sometimes considered to be more flexible than the native ones (see Chapter 7). Such a conclusion seems unfounded since X-ray diffraction can yield straightforwardly only the structure of the macrocyclic ring averaged over time and space, not its mobility. As a matter of fact, native CyDs are more flexible, and thus more difficult to freeze, than permethylated ones. This fact is frequently overlooked since the above mentioned averaging is not taken into account. As shown above, NMR spectra in solution and in the solid state are much more sensitive to CyD flexibUity and clearly prove their nonrigidity. 

Treating the hepta-iodo-) -CyD derivative with NaNs in DMF gave, in 96% yield, the hepta-azide, which was methylated using a large excess of Mel and NaH to afford the permethylated derivative quantitatively. Treatment with PhsP followed by aqueous NH3 furnished the hepta-amino-/ -CyD. The disaccharide[Pg.36]

By reacting with a rigid disulfonyl chloride, j8-CyD 6-tosylate is readily disulfo-nated to give 6A,6C,6E-trisulfonylated j8-CyDs in good yields [80]. Novel j8-CyD-based terpyridine derivatives have been prepared by the coupling of terpyridine with mono-hydroxy permethylated j8-CyD. The CyD dimer was synthesized by reaction of terpyridine-dicarbonitrile with an excess of 6-tosyl-j8-CyD [81]. The synthesis of the chloroacetylate derivatives of a-, fi-, and y-CyDs has been reported [82]. 

Heptakis-6-(tert-butyldimethylsilyl)-) -CyD was treated with excess t-butylsilyl chloride (TBSCl) resulting in a single octasilyl derivative at the more acidic C2 position. Permethylation under strongly basic conditions (Mel, NaH, THF), led to migration of the 2-O-silyl group to the 3-0 position. Treatment of the products with tetrabutylammonium fluoride gave the versatile monofunctionalized ) -CyDs in high yields [94]. 

A )8-CyD derivative modified with p-xylylenediamine at the 3-position, mono-3-[4-(aminomethyl)benzylamino]-yS-CyD, was prepared by the reaction of ) -CyD-2,3-manno-epoxide with p-xylylenediamine [97]. The three isomeric mono-2-, 3-, or 6-hydroxy permethylated yS-CyDs are good precursors for a wide variety of monofunctionalized permethyl yS-CyDs. As protecting groups, the benzyloxy group was used for C2, and the t-butyldimethylsilyl group for C6. Mono-C3 hydroxy CyD was obtained by partial methylation of 2,6-dimethyl CyD [98]. 

The CyD analogue with an isophthaloyl spacer 62 shows a binding ability for p-nitrophenol almost the same as that of permethylated fi-CyD, whereas the binding constant of the CyD analogue with a 2,6-pyridinedicarbonyl spacer 63 is only one thirteenth of that of permethylated j8-CyD [173]. 

Interestingly, capillary columns with permethylated-jS-CyD were successfully used for the separation of isotopomers [22],... 

A wide variety of native and derivatized CyDs are available for use as mobile phase additives in HPLC. In liquid chromatography to study the interaction of CyDs with guest molecules, the information about cydodextrin adsorption on the stationary phase is very substantial. It should be noted that the separation ability of bonded CyDs and CyDs added to the mobile phase in HPLC is not always the same (see below). To assess the adsorption of CyDs on the stationary phase, the chromatographic properties of native and permethylated CyDs applied in RP18 and porous graphitic carbon (PGC) column have been studied [25-29]. On the RP18 column the adsorption of yS-CyD is much stronger than that of a- or y-CyDs. On the PGC, the order of elution is a- < < y-CyD, in accordance with the increase of... 

The chromatographic behavior of mandelic acid and its esters was studied in reversed-phase HPLC (RP-HPLC) with a-, p-, y-, and permethylated-) -CyD as additive to the mobile phase. It was found that native CyDs do not recognize enantiomers of esters although they form relatively stable 1 1 complexes with them. Estimated stability constants for these guests are presented in Table 5.1 [43]. 

Tlie first chiral separation with open-tubular columns in SFC was published by Roder et al. in 1987 [39]. Schurig and co-workers [40] linked permethylated fi-CyD via an octamethylene spacer to polydimethylsiloxane forming a chiral polymer Chirasil-Dex. The polymer was immobilized on the inner surface of fused-silica capillaries and the capillaries were used for so-called unified chromatography including GC, LC, SFC, and capillary electrochromatography (CEC). 

In 1992 Mayer and Schurig showed for the first time the possibility of enantioseparations in open tubular capillaries modified with a permethylated CyD derivative. This technique was used later with different chiral selectors but did not mature to become the method of choice for CEC enantioseparations, most likely due to the following conflict inherent in this technique. For a separation which occurs on the mobile phase/stationary phase interface and not in the bulk solution, retention of the analyte on the capillary wall (chiral stationary phase) is necessary for achieving a separation. On the other hand, any retentive analyte-capillary wall interactions are associated with a drastic decrease in peak efficiency in capillary electromigration techniques. However, this study stimulated research in both capillary enantioseparation techniques and in the use of CyD-based CSPs for CEC enantioseparations. 

Permethylation of hydroxyl groups makes the 06 side narrower because of the sharp inclination of 2,3,6-tri-O-methylglucose units caused by the steric hindrance between methyl groups bonded to 03 and 02 of adjacent 2,3,6-tri-O-methylglucose unit. As the result, m-nitroaniline [187] and p-nitrophenol [197] are included with their hydroxyl or amino group located at the 06 side, that is, in the orientation upside down compared with the corresponding complex with the parent a-CyD (Fig. 

The stabilizing effect of permethylation in the binding of some guests to a-CyDs was explained by the enlargement of the hydrophobic cavity [33]. 

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