Cyclodextrins etheric derivatives

In application, the most important chemically modified CDs are the ether derivatives, such as hydroxypropyl-, methyl-, ethyl-CDs. These cyclodextrins etheric derivatives (CEDs) with the improved solubility, encapsulation ability and low toxicity have aheady been commercialized and widely used. The CEDs could be prepared in two ways. One way is that the CD reacts with the free hydroxyls such as dimethyl sulfate, diethyl sulfate, alkyl halides and epoxides. The other way is by sulfonic ester transformation. 

RJ Tait, DJ Skanchy, DO Thompson, NC Chetwyn, DA Dunshee, RA Ra-jewski, VJ Stella, JF Strobaugh. Characterization of sulphoalkyl ether derivatives of 6-cyclodextrin by capillary electrophoresis with indirect UV detection. J Pharm Biomed Anal 10 615-622, 1992. 

Microcrystalline cellulose triacetate, cyclodextrin- and crown ether-derived CSPs, as well as some chiral synthetic polymers, achieve enantiomer separation primarily by forming host-guest complexes with the analyte in these cases, donor-acceptor interactions are secondary. Solutes resolved on cyclodextrins and other hydrophobic cavity CSPs often have aromatic or polar substituents at a stereocenter, but these CSPs may also separate compounds that have chiral axes. Chiral crown ether CSPs resolve protonated primary amines. 

Luna, EA, DG Vander Velde, RJ Tait et al. (1997). Isolation and characterization by NMR spectroscopy of three monosubstituted 4-sulfobutyl ether derivatives of cyclomaltoheptaose ( 8-cyclodextrin). Carbohydrate Research, 299(3), 111-118. 

Miscellaneous Soft-Template Methods Novel Y-junction PANI-NTs, accompanied with nanorods, have been selectively prepared using in situ self-assembly of water-soluble Fe304 nanoparticles coated with PEG(5)-nonylphenylether and cyclodextrin as templates and pH control in an aqueous medium [373]. A chemical oxidative route to synthesize oriented arrays of conducting PANI-NTs in HCl solution by hydrogen-bonding directionality in the presence of a crown ether derivative (CE-SO3K) has also been reported [374]. 

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. 

Elek J, Mangelings D, Ivanyi T, Lazar I, Vander Heyden Y. Enantioselective capillary electrophoretic separation of tryptophane and tyrosine-methylesters in a dual system with a tetra-oxadiaza-crown-ether derivative and a cyclodextrin. J. Phartn. Biotned. Anal. 2005 38 601-608. 

Functional artificial ion channels have been reported which illustrate the general criteria. The most obvious course is to prepare oligopeptides with hi helical content (S). Other reported systems are bas on cyclo xtrin (6), polymeric crown ethers (7), and "bouquet" shaped crown ether and cyclodextrin motifs (8). One of the most active systems is a simple tris-crown ether derivative repented by Gokel for the transport of sodium ions(9). All of these systems envisage a uni- or bi-molecular transmembrane structure, similar to the gramicidin structurd paradigm. 

Grafting a receptor moiety onto rare earth metal complexes led to a new series of CSRs operating in water. Dy + complexes with cyclodextrin derivatives 75 (scheme 16) were synthesized as Itybrid-type CSRs in which the triaminotetracarboxylic acid moiety chelates the rare earth ion while the chiral cyclodextrin accommodates aromatic compounds in its hydrophobic pocket (Wenzel et al., 1994, 2000). Wenzel et al. (2003) demonstrated that the commercially available sulfonated and carboxymethylated cyclodextrins are effective CSRs for water-soluble aromatic cations in the presence of Dy + or Yb " ". A crown ether derivative, which accommodates primary ammonium cations, also forms chelates with rare earth... 

Appllca.tlons. The first widely appHcable Ic separation of enantiomeric metallocene compounds was demonstrated on P-CD bonded-phase columns. Thirteen enantiomeric derivatives of ferrocene, mthenocene, and osmocene were resolved (7). Retention data for several of these compounds are listed in Table 2, and Figure 2a shows the Ic separation of three metallocene enantiomeric pairs. P-Cyclodextrin bonded phases were used to resolve several racemic and diastereomeric 2,2-binaphthyldiyl crown ethers (9). These compounds do not contain a chiral carbon but stiU exist as enantiomers because of the staggered position of adjacent naphthyl rings, and a high degree of chiral recognition was attained for most of these compounds (9). 

The condensation reactions described above are unique in yet another sense. The conversion of an amine, a basic residue, to a neutral imide occurs with the simultaneous creation of a carboxylic acid nearby. In one synthetic event, an amine acts as the template and is converted into a structure that is the complement of an amine in size, shape and functionality. In this manner the triacid 15 shows high selectivity toward the parent triamine in binding experiments. Complementarity in binding is self-evident. Cyclodextrins for example, provide a hydrophobic inner surface complementary to structures such as benzenes, adamantanes and ferrocenes having appropriate shapes and sizes 12) (cf. 1). Complementary functionality has been harder to arrange in macrocycles the lone pairs of the oxygens of crown ethers and the 7t-surfaces of the cyclo-phanes are relatively inert13). Catalytically useful functionality such as carboxylic acids and their derivatives are available for the first time within these new molecular clefts. 

Piel et al. [109] studied the pharmacokinetics of miconazole after intravenous administration to six sheep (4 mg/kg) of three aqueous solutions - a marketed micellar solution containing polyoxyl-35 castor oil was compared with two solutions both containing 50 pM lactic acid and a cyclodextrin derivative (100 pM hydro-xylpropyl-/l-cyclodextrin or 50 pM sulfobutyl ether (SBE7)-/i-cyclodextrin. This work demonstrated that these cyclodextrin derivatives have no effect on the pharmacokinetics of miconazole by comparison with the micellar solution. The plasma concentration-time curves have shown that there is no significant difference between the three solutions. 

Ring-opening with heteroatomic nucleophiles is certainly among the most thoroughly studied behavior of epoxides, and this reaction continues to be a versatile workhorse of synthetic utility. This is exemplified in the recent literature by the examples of the p-cyclodextrin-catalyzed aminolysis of simple epoxides by aniline derivatives (i.e., 53 - 54) <00SL339> and the synthesis of oxa-azacrown ethers through the treatment of Ws-epoxides 55 with diamines 56. Yields in the latter synthesis are sensitive to the size of the macrocycle and substitution on the bis-epoxide <00TL1019>. 

An extremely important aspect in pharmaceutical research is the determination of drug optical purity. The most frequently applied technique for chiral separations in CZE remains the so-called dynamic mode where resolution of enantiomers is carried out by adding a chiral selector directly into the BGE for in situ formation of diastereomeric derivatives. Various additives, such as cyclodextrins (CD), chiral crown ethers, proteins, antibiotics, bile salts, chiral micelles, and ergot alkaloids, are reported as chiral selectors in the literature, but CDs are by far the selectors most widely used in chiral CE. 

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). 

The n values used here are derived from di-n-butylether/water partition coefficients since the ether phase was thought to better simulate the environment of the cavity of cyclodextrins. Eq 38 indicates that the principal driving force for the inclusion complex formation with P-cyclodextrin is the dehydration from surroundings of the guest molecule. 

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