Cyclodextrin hydrolysis

Two further examples of similar types of analyses using the RI detector is afforded by the separation of the products of P-cyclodextrin hydrolysis and of the partial hydrolysis of galaction. 

Of particular importance for modifications of starch are the enzyme degradation products such as glucose symps, cyclodextrins, maltodextrins, and high fmctose com symps (HFCS). Production of such hydrolysis products requites use of selected starch-degrading enzymes such as a-amylase,... 

Various chemical species influence the rates of hydrolysis of penicillins, e.g. metal ions (Cu >Zn >Ni Co ) (80JCS(P2)1725), carbohydrates (78MI51101), certain amine-containing catechol derivatives (69JPS1102) and /3-cyclodextrin (71JA767). Some of these even show some of the characteristics of enzyme-catalyzed hydrolyses. 

Nishioka and Fujita78) have also determined the Kd values fora- and (S-cyclodextrin complexes with p- and/or m-substituted phenyl acetates through kinetic investigations on the alkaline hydrolysis of the complexes. The Kd values obtained were analyzed in the same manner as those for cyclodextrin-phenol complexes to give the Kd(X) values (Table 5). The quantitative structure-activity relationships were formulated as Eqs. 30 to 32 ... 

Quantitative structure-reactivity analysis is one of the most powerful tools for elucidating the mechanisms of organic reactions. In the earliest study, Van Etten et al. 71) analyzed the pseudo-first-order rate constants for the alkaline hydrolysis of a variety of substituted phenyl acetates in the absence and in the presence of cyclodextrin. The... 

The rate acceleration imposed by 0-cyclodextrin was explained in terms of a microsolvent effect 6> The inclusion of the substrate within the hydrophobic cavity of cyclodextrin simulates the changes in solvation which accompany the transfer of the substrate from water to an organic solvent. Uekama et al.109) have analyzed the substituent effect on the alkaline hydrolysis of 7-substituted coumarins (4) in the... 

An artificial metalloenzyme (26) was designed by Breslow et al. 24). It was the first example of a complete artificial enzyme, having a substrate binding cyclodextrin cavity and a Ni2+ ion-chelated nucleophilic group for catalysis. Metalloenzyme (26) behaves a real catalyst, exhibiting turnover, and enhances the rate of hydrolysis of p-nitrophenyl acetate more than 103 fold. The catalytic group of 26 is a -Ni2+ complex which itself is active toward the substrate 1, but not toward such a substrate having no metal ion affinity at a low catalyst concentration. It is appearent that the metal ion in 26 activates the oximate anion by chelation, but not the substrate directly as believed in carboxypeptidase. 

A chromatogram demonstrating the separation of the hydrolysis products of p-cyclodextrin is shown in figure 19. 

Isoxazolines 38 and 39 were obtained in different ratios by direct cycloaddition of 4-t-butylbenzonitrile oxide with acids 35 (R = H, path B) and by the intermediate formation of cyclodextrin derivatives 36 and 37 followed by basic hydrolysis and acidification (path A). The reversed regioselectivity as well as an increased rate of the cycloaddition step could be explained through the temporary association of the nitrile oxide with the cyclodextrin to give the inclusion complex 40 <06CEJ8571>. 

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... 

Figure 5.5. The cyclodextrin catalysis of phenylester hydrolysis (Saenger, 1980).

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)... 

The effects of cyclodextrins on this reaction, while potentially of great interest, have been rarely studied, presumably because amide hydrolysis is generally slow and so tedious to study. As a result, only two examples are considered here. 

The photoreaction of 7V-(12-dodecanoic acid)-benzoylformamide 170 in solution and in /J-cyclodextrin or carboxymethylamylose complexes indicated that major products are those of hydrolysis to mandelamide 171 and to the corresponding aldehyde 172 (equation 113)169. 

Cyclodextrins slow the rate of hydrolysis of benzaldehyde dimethyl acetal, PhCH(OMe)2, in aqueous acid as the substrate binds in the cyclodextrin s cavity, producing a less reactive complex. Added alternative guests compete for the binding site, displacing the acetal and boosting hydrolysis. 

Molecular dynamics free-energy perturbation simulations utilizing the empirical valence bond model have been used to study the catalytic action of -cyclodextrin in ester hydrolysis. Reaction routes for nucleophilic attack on m-f-butylphenyl acetate (225) by the secondary alkoxide ions 0(2) and 0(3) of cyclodextrin giving the R and S stereoisomers of ester tetrahedral intermediate were examined. Only the reaction path leading to the S isomer at 0(2) shows an activation barrier that is lower (by about 3kcal mol ) than the barrier for the corresponding reference reaction in water. The calculated rate acceleration was in excellent agreement with experimental data. ... 

The acid hydrolysis of alkyl nitrites (Scheme 53) is inhibited by the presence of /I-cyclodextrin (CD) owing to the formation of 1 1 inclusion complexes that are unre-active or much less reactive than the RONO not complexed. The degree of inhibition... 

Numerous examples of modiflcations to the fundamental cyclodextrin structure have appeared in the literature.The aim of much of this work has been to improve the catalytic properties of the cyclodextrins, and thus to develop so-called artificial enzymes. Cyclodextrins themselves have long been known to be capable of catalyzing such reactions as ester hydrolysis by interaction of the guest with the secondary hydroxyl groups around the rim of the cyclodextrin cavity. The replacement, by synthetic methods, of the hydroxyl groups with other functional groups has been shown, however, to improve remarkably the number of reactions capable of catalysis by the cyclodextrins. For example, Breslow and CO workersreported the attachment of the pyridoxamine-pyridoxal coenzyme group to beta cyclodextrin, and thus found a two hundred-fold acceleration of the conversion of indolepyruvic acid into tryptophan. 

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