Cyclodextrin substituted

Schmitt, U., Ertan, M., and Holzgrabe, U. (2004). Chiral capillary electrophoresis facts and fiction on the reproducibility of resolution with randomly substituted cyclodextrins. Electrophoresis 25, 2801-2807. 

A more attractive chemo-enrymatic approach for the production of he-mithiocyclodextrins has been developed. More than ten years ago, cyclodextrin glucosyltransferase (CGTase) was shown to use a-maltosyl fluoride for the synthesis of a-, p-, and y-cyclodextrins [47] and has been used for the chemoenzymatic synthesis of regioselectively substituted cyclodextrins [48]. For this purpose, 4-thio-a-maltosyl fluoride (58) was easily prepared from (45). Incubation of (58) in the presence of pure CGTases afforded hemithiocyclodex-trins (57a), (57b) and (57c) isolated in 14,16 and 15% yields respectively [49]. 

Cyclodextrin-substituted molecular channel approaches have now been extended to include acyl substituents through a covalent bond formation. Stearoyl and methyl cholate-substituted cyclodextrins 10 and 11, respectively, have been synthesized. It may be worthwhile commenting on the molecular design of methyl cholate-substituted a-cyclodextrin. All of the ether groupings are convergent at the inner side of the steroidal backbone of a bent structure to make the molecule amphiphilic. Once the cyclodextrin derivative is incorporated into the membrane phase, it may easily be expected that the ether parts are assembled inside the channel in the sea of hydrophobic lipid molecules and the hydrophobic steroidal skeletons cover its outside to stabilize the inner hydrophilic pore (Figure 13). 

Recently, X-ray analysis of /J-cyclodextrin having a t-butyl-thio moiety at the C(6) position was reported as the first example of mono-substituted cyclodextrin (38). Interestingly, a single molecule of this cyclodextrin behaves as the host at its cavity, on the one hand, and also as the guest at the t-butyl moiety, on the other hand, as shown in Fig. 7. 

This interesting result strongly suggests that even for the substituted cyclodextrins the capacity of inclusion formation is much the same as for the parent cyclodextrin. Therefore, we may extend the basic concept of the structure of cyclodextrin inclusion to molecular design for the preparation of artificial enzymes having satisfactory substrate specificities and catalytic activities. 

W. A. Konig, B. Gehrcke, D. Ischeln, P. Evers, J. Donnecke and W. Wang, New selectively substituted cyclodextrins as stationary phases for the analysis of chiral constituents of essential oils , / High Resolut. Chromatogr. 15 367-372 (1992). 

Tabushi, I., (1986) Chiral selection and chiral induction by the use of regiospecifically di-(or poly Substituted cyclodextrins Pure Appl. Chem. 58, 1529-1534. 

The extent of stereoselectivity in the chiral synthesis can be checked by determining the enantiomeric excess of the optically active olefins in the products. The optical purity was determined by gas chromatographic resolution of enantiomers by means of an optically active column. Thermostable substituted cyclodextrins are well suited as asymmetric phases (206). The trimer, 2,4-dimethyl-l-heptene, was resolved into its enantiomers by capillary gas chromatography with an octakis(6-0-methyl-2,3-r/-0-pentyl-)-7-cyclodextrine phase. 

We have also examined the use of cyclodextrin-derived artificial enzymes in promoting bimolecular aldol reactions, specifically those of m-nitrobenzaldehyde (57) and ofp-t-butylbenzaldehyde (58) with acetone [141]. Here, we examined a group of mono-substituted cyclodextrins as catalysts (e.g. 59), as well as two disubstituted (3-cyclodextrins (e.g. 60) (10 catalysts in all). They all bound the aldehyde components in the cyclodextrin cavity and used amino groups of the substituents to convert the acetone into its enamine. An intracomplex reaction with 58 and hydrolysis of the enamine product then afforded hydroxyketone 61 (cf. 62). These catalysts imitate natural enzymes classified as Class I aldolases. 

Substituted cyclodextrin derivatives are also available see Section 17. 

Cyclodextrins are crystalline, nonhygroscopic, cyclic oligosaccharides derived from starch see Cyclodextrins). Sulfobutylether P-cyclodextrin is an amorphous, anionic substituted P-cyclodextrin derivative (see Section 8) other substituted cyclodextrin derivatives are also available see Section 17). 

B. Maas, A. Dietrich, V. Karl, A. Kaunzinger, D. Lehmann, T. Kdpke and A. Mosandl. Tert-Butyldimethylsilyl-substituted cyclodextrin derivatives as versatile chiral stationary phases in capillary GC. J. Microcol. Sep., 5, 421-427 (1993). 

Stalcup, A. M. Comparison ofthe enantioselectivity of phenethyl- and naphthyl-ethyl-carbamate substituted cyclodextrin bonded phases,/. Liq. Chromatogr., 1993,... 

Chakraborty, M., Mitseva, P.I. and Bart, HJ. (2006). Selective separation of toluene from n-heptane via emulsion liquid membranes containing substituted cyclodextrins as carriers. Sep. Sci. Technol., 41, 3539-52. 

FIGURE 18. Structure of a calixarene thioether (a), and a model for the arrangement of substituted cyclodextrins in a monolayer (b). Reprinted respectively with permission from References 225 and 227 Copyright (1997, 1996) American Chemical Society... 

Reetz et al. prepared /3-cyclodextrin-modified diphosphine 18 and a series of derivatives by phosphinomethylation of the corresponding amino-substituted cyclodextrin precursors [25], The ligands were used in biphasic hydroformylation of 1-octene and competitive hydrogenation of 1-alkenes, with rather poor results. The chiral cavity in the backbone might achieve molecular recognition of certain pro-chiral substrates and thus provide enantioselectivity in the products. 

Complexes of these substituted cyclodextrins with zinc ion showed larger rates of hydration of carbon dioxide than the compounds without cyclodextrin although the absolute catalytic rate constants are lower than their enzymatic counterparts by many orders of magnitude, especially the second compound [38]. 

In addition to surfactants and polymers, other compoimds have also been studied as stabilizers. Water-soluble polyoxometallate-stabilized nanoparticles display satisfactory activities in Suzuki, Heck and Stille reactions in aqueous solution (Table 2) [32], Thiol-substituted cyclodextrins have been employed as stabilizers for palladium coUoids, which were active in Suzuki reactions, although the stability was limited [33],... 

A. Ueno, F. Moriwaki, Y. Hino, T. Osa, Ester hydrolysis by a 2-naphthylacetyl-substituted /-cyclodextrin, J. Chem. Soc., Perkin Trans. 2, 1985, 921-923. 

Dall asta, C, G Ingletto, R Corradini, G Galaverna and R Marchelli (2003). Fluorescence enhancement of aflatoxins using native and substituted cyclodextrins. Journal of Inclusion Phenomena and Macrocyclic Chemistry, 45(3 ), 257-263. 

Deoxy-3-imidazolyl-substituted cyclodextrins are covered in Chapter 4, and bis-(glucos-3-yl)-bipyridine in Chapter 14. 

The number above the peaks denote the number of substituted hydroxy propyl groups per cyclodextrin moiety. It is seen that there is a (more or less) symmetrical distribution of substituents about a mean of 6 hydroxyl groups reacted per cyclodextrin structure. There also appears to be a minimum of about 2 and a maximum of 12 substituents per moiety. This distribution, that results from substitution reaction, shows that the substituted cyclodextrin phases are not necessarily homogeneous substances and that their net chromatographic properties, including their chiral selectivity, will be the average effect of a number of differently substituted hydroxyl groups. 

For method optimization of chiral separations the type and concentration of the chiral selector has to be specifically considered in addition to factors also important in achiral CE such as pH, molarity and type of the background electrolyte, and buffer additives. When using randomly substituted cyclodextrins as chiral selectors testing of different batches of the cyclodextrin and samples from different suppliers is... 

In the area of cyclodextrin ethers the -compound has been converted into a set of five tris-Tbdms ethers, all substituted at their various 6-positions, which were separated by hplc and characterized by n.m.r. spectroscopy. Related work applied to y-cyclodextrin gave the various 6,6 -disubstituted ethers. 5-Bromo-l-pentene was used to produce the 2-0-mono-4-pentenyl ether of P-cyclodextrin which was then permethylated and the product was chemically bonded to silica gel to form an efficient hplc stationary phrase for the separation of enantiomers. Peroctyl a-cyclodextrin has been studied as a chiral receptor for the ephedrinium ion. Various octyl ethers of a-, P- and y-cyclodextrin ranging in their substitution from the diethers to completely alkylated products were characterized by electrospray mass spectrometry and n.m.r. methods applied to methylated derivatives. The 2,6-didodecyl derivative of p-cyclodextrin has been used as a potentiometric sensor. In the field of aromatic ethers, naphthyl carboxylate substituents have been bonded at the 6-positions and the products were able to transfer excitation energy to complexed merocyanine held in the cavities of those molecules. These phototransfer processes were extremely efficient.P-Substituted cyclodextrin derivatives with p-allyloxybenzoyl or various benzyl substituents at 0-2 or 0-3 were incorporated by hydrosilylation to give hydromethylpolysiloxane polymers used as chiral phases for chromatographic resolution of enantiomers. Cyclodextrins with complex benzyl-like eth are illustrated in 22 and 23. The latter were prepared as artificial redox enzymes. 

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