Cyclodextrin Esters

FIGURE 2. Self-assembly of amphiphiUic cyclodextrin esters in (a) py-d and (b) thf-4g... 

Hirayama, F., Ogata, T., Yano, H. et al. Release characteristics of a short-chain fatty add, n-butyric acid, from its (3-cyclodextrin ester conjugate in rat biological media. J. Pharm. Sci. 2000, 89, 1486-1495. 

By contrast, Table VII shows that nickel and zinc will catalyze the deacetylation of pyridine carboxaldoxime acetate, but the cyclodextrin ester does not add anything to the rate. The ester will not increase the metal-catalyzed hydrolysis rate of materials which if bound into the cavity would have the group held in the wrong place. This fits a geometric picture—that is, that the substrate must both bind into the cavity and in addition have the proper orientation with respect to the attacking group within that cavity. But still the cooperativity is rather modest. 

Figure 3.3 Complementary diastereoselectivity in the acylation of ft-cyclodextrin with the acid chloride of Ibuprofen and in the hydrolysis of the corresponding cyclodextrin ester ...

Cyclodextrin Esters. - CDs with mono-6-benzoate or monosubstituted 6-benzoates and related compounds with benzoylamino-deoxy groups in C-6 positions have been used for enantio-differentiating photoisomerization of (Z)-cyclooctene to the chiral (E)-isomer. ... 

Choisnard L, Geze A, Putaux JL, Wong YS, Wouessidjewe D. Nanoparticles of beta-cyclodextrin esters obtained by self-assembling of biotransesterified betacydodextrins. Biomacromolecules. 2006 7 515-20. 

The maximal rate constants k and binding constants of j8-cyclodextrin-ester... 

In these equations, Dmax is the larger of the summed values of STERIMOL parameters, Bj, for the opposite pair 68). It expresses the maximum total width of substituents. The coefficients of the ct° terms in Eqs. 37 to 39 were virtually equal to that in Eq. 40. This means that the a° terms essentially represent the hydrolytic reactivity of an ester itself and are virtually independent of cyclodextrin catalysis. The catalytic effect of cyclodextrin is only involved in the Dmax term. Interestingly, the coefficient of Draax was negative in Eq. 37 and positive in Eq. 38. This fact indicates that bulky substituents at the meta position are favorable, while those at the para position unfavorable, for the rate acceleration in the (S-cyclodextrin catalysis. Similar results have been obtained for a-cyclodextrin catalysis, but not for (S-cyclodextrin catalysis, by Silipo and Hansch described above. Equation 39 suggests the existence of an optimum diameter for the proper fit of m-substituents in the cavity of a-cyclodextrin. The optimum Dmax value was estimated from Eq. 39 as 4.4 A, which is approximately equivalent to the diameter of the a-cyclodextrin cavity. The situation is shown in Fig. 8. A similar parabolic relationship would be obtained for (5-cyclodextrin catalysis, too, if the correlation analysis involved phenyl acetates with such bulky substituents that they cannot be included within the (5-cyclodextrin cavity. 

Cyclodextrins, toroidal molecules composed of 6, 7 and 8 D-glucose units, are now commercially available at reasonable cost. They form inclusion compounds with a variety of molecules and often differentially include sulfoxide enantiomers29,30. This property has been used to partially resolve some benzyl alkyl, phenyl alkyl and p-tolyl alkyl sulfoxides. The enantiomeric purities after one inclusion process ranged from 1.1 % for t-butyl p-tolyl sulfoxide to 14.5% for benzyl r-butyl sulfoxide. Repeating the process on methyl p-tolyl sulfoxide (10) increased its enantiomeric purity from 8.1% to 11.4% four recrystallizations raised the value to 71.5%. The use of cyclodextrins in asymmetric oxidations is discussed in Section II.C.l and in the resolution of sulfmate esters in Section II.B.l. 

Mikolajczyk and coworkers have summarized other methods which lead to the desired sulfmate esters These are asymmetric oxidation of sulfenamides, kinetic resolution of racemic sulfmates in transesterification with chiral alcohols, kinetic resolution of racemic sulfinates upon treatment with chiral Grignard reagents, optical resolution via cyclodextrin complexes, and esterification of sulfinyl chlorides with chiral alcohols in the presence of optically active amines. None of these methods is very satisfactory since the esters produced are of low enantiomeric purity. However, the reaction of dialkyl sulfites (33) with t-butylmagnesium chloride in the presence of quinine gave the corresponding methyl, ethyl, n-propyl, isopropyl and n-butyl 2,2-dimethylpropane-l-yl sulfinates (34) of 43 to 73% enantiomeric purity in 50 to 84% yield. This made available sulfinate esters for the synthesis of t-butyl sulfoxides (35). 

The rate of formation of sulphoxides from sulphides and iodine in aqueous solution has been found to be relatively slow. It may be, however, accelerated by certain nucleophiles, such as phthalate ion S hydrogen phosphate ion and E(-cyclodextrin phosphate ion . The selective oxidation of JV-acetylmethionine and N-acetylmethionine methyl ester to the corresponding S-oxides was achieved using iodine in the presence of dicarboxylate ions. 

The alkaline hydrolysis of p-nitrophenyl oxodecanoates [36] has been studied in the absence and presence of cyclodextrins (Cheng et al., 1985). These flexible keto-esters have either a 4-, 5- or 6-oxo substituent [36], and their rates of hydrolysis can be compared with unsubstituted ester [37]. The... 

An additional example is the observed moderate acceleration in the cleavage of particular phenyl esters in the presence of a cyclodextrin. In such cases, the bound ester is attacked by an hydroxyl group on the cyclodextrin to yield a new ester. There was found to be a significant enhancement of phenol release from meta-substituted phenyl acetate on interaction with cyclodextrin (relative to other esters which do not fit the cavity so well) (Van Etten, Clowes, Sebastian Bender, 1967). During the reaction, the acyl moiety transfers to an hydroxyl group on the... 

The hydrolysis of esters by the nickel derivative (271) provided an early example of the use of a metal-capped cyclodextrin as a catalyst (shown here as its p-nitrophenyl acetate inclusion complex) (Breslow Overman, 1970 Breslow, 1971). The synthesis of this host involves the following steps (i) covalent binding of the pyridine dicarboxylic acid moiety to cyclodextrin, (ii) coordination of Ni(n) to this species, and (iii)... 

Provided due attention is paid to the potential deprotonation of the substrate, and of the cyclodextrins (VanEtten et al., 1967a,b Gelb et al., 1980, 1982 Tee and Takasaki, 1985), the value of Ks should not be pH dependent. However, for many reactions, such as the widely studied ester cleavage, ku, kc, and k2 are all dependent on the pH of the medium. This makes direct comparisons between the observed constants for different CD-mediated reactions either difficult or problematical. However, in general, the ratios kc/ku and k2/ku are independent of pH and so are more useful for comparative purposes. 

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