Cyclohexaamylose

Note. The cyclic oligosaccharides arising from enzymic transglycosylation of starch have been referred to as Schardinger dextrins. These names (and those of the cyclohexaamylose type) are not recommended, but the abbreviation CD is tolerated. 

C36H6 O30 6 H20 Cyclomaltohexaose hexahydrate (cyclohexaamylose hexahydrate, a-cyclodextrin hexahydrate) (CHXAMH01)125 (CHXAMH02)126... 

CaeHeoOao 6 H20 Cyclomaltohexaose, hexahydrate (cyclohexaamylose hexahy- CHXAMH, 01, 32 371... 

Within a similar series of reagents, complexing tendency toward the different cycloamyloses can be qualitatively correlated with the size of the reagent. All three cycloamyloses, for example, are effectively precipitated from aqueous solution by benzene, but only cyclooctaamylose is precipitated by anthracene. Similarly, for cycloheptaamylose, bromobenzene is a more effective precipitant than benzene, whereas the reverse is true for cyclohexaamylose. Discriminating precipitants such as these have been incorporated by French and associates (1949) and by Cramer and Henglein (1958) into schemes for the separation of cyclohexa-, cyclohepta-, and cyclooctaamylose. 

Fig. 7. Corey-Pauling-Koltun molecular models of cyclohexaamylose complexes with p-f-butylphenyl acetate (top) and wi-t-butylphenyl acetate (bottom).

More recently, Kaiser and coworkers reported enantiomeric specificity in the reaction of cyclohexaamylose with 3-carboxy-2,2,5,5-tetramethyl-pyrrolidin-l-oxy m-nitrophenyl ester (1), a spin label useful for identifying enzyme-substrate interactions (Flohr et al., 1971). In this case, the catalytic mechanism is identical to the scheme derived for the reactions of the cycloamyloses with phenyl acetates. In fact, the covalent intermediate, an acyl-cyclohexaamylose, was isolated. Maximal rate constants for appearance of m-nitrophenol at pH 8.62 (fc2), rate constants for hydrolysis of the covalent intermediate (fc3), and substrate binding constants (Kd) for the two enantiomers are presented in Table VIII. Significantly, specificity appears in the rates of acylation (fc2) rather than in either the strength of binding or the rate of deacylation. 

In contrast to the reaction of cyclohexaamylose with 1, no enantiomeric specificity is observed in the reaction of this material with cyclohepta-amylose (Paton and Kaiser, 1970). This loss of specificity upon increasing... 

The reaction of cyclohexaamylose with a series of p-carboxyphenyl esters is an example of a decelerating effect which may be clearly attributed to nonproductive binding. Rate effects imposed by cyclohexaamylose on the hydrolyses of three such esters are summarized in Table IX. As the hydrophobicity of the ester function is increased by alkyl substitution, the hydrolysis is inhibited the stability of the inclusion complex, on the other... 

Maximal Rate Constants and Dissociation Constants of Cyclohexaamylose Complexes of p-Carboxyphenyl Esters at 25°a... 

Manifestation of specificity in maximal rate constants rather than in stability constants is illustrated particularly well by the cyclohexaamylose-accelerated release of fluoride ion from Sarin. Although the inclusion complex of (rate acceleration is much larger for the (—)-enantiomer. Specificity is equally dramatic in... 

Enantiomeric Specificity in the Reactions of Cyclohexaamylose with Chiral Organophosphorus Substrates... 

Regardless of the relative importance of polar and nonpolar interactions in stabilizing the cyclohexaamylose-DFP inclusion complex, the results derived for this system cannot, with any confidence, be extrapolated to the chiral analogs. DFP is peculiar in the sense that the dissociation constant of the cyclohexaamylose-DFP complex exceeds the dissociation constants of related cyclohexaamylose-substrate inclusion complexes by an order of magnitude. This is probably a direct result of the unfavorable entropy change associated with the formation of the DFP complex. Thus, worthwhile speculation about the attractive forces that lead to enantiomeric specificity must await the measurement of thermodynamic parameters for the chiral substrates. 

In contrast to the effect of cycloheptaamylose, cyclohexaamylose depresses the rates of decarboxylation of unionized 8-keto acids (Straub and Bender, 1972). Since conformational effects depend largely on the geometry of binding, it is not surprising to find high sensitivity to the size of the cycloamylose cavity. Apparently, the smaller cyclohexaamylose cavity cannot accomodate the cyclic transition state for acidic decarboxylations. 

An additional example of a cycloamylose-induced rate acceleration which may be reasonably attributed to a conformational effect is the facilitation of the transfer of the trimethylacetyl group from the phenolic oxygen of 9 to the aliphatic oxygen of the adjacent hydroxymethyl group to form 10. This intramolecular transesterification is remarkably enhanced relative to a comparable intermolecular reaction,6 and occurs, at pH 7.0 and 25.5°, with a rate constant of 0.0352 sec-1 (Griffiths and Bender, 1972). An even larger rate enhancement is achieved upon inclusion of this material within the cyclohexaamylose cavity—fc2 = 0.16 sec-1. This fivefold acceleration cannot be satisfactorily explained either by a microsolvent effect which would be expected to depress the rate of the reaction or, at this pH, by covalent... 

The rate effects imposed by this derivative, however, are dependent on the structure of the substrate. For example, the hydrolysis of 8-acetoxy-5-quinoline-sulfonate (AQS), a large substrate which cannot be included within the cyclohexaamylose cavity, is not enhanced by this derivative. Moreover, in contrast to the effects of unmodified cycloamyloses on the hydrolyses of nitrophenyl acetates, the rate accelerations imposed by this... 

In an attempt to prepare a catalytically active cycloamylose derivative which would retain the binding properties of an unmodified cycloamylose,7 Gruhn and Bender (1971) attached a relatively small hydroxamate function to a secondary hydroxyl group of cyclohexaamylose. The initial and most important step in the synthetic sequence is the reaction of ionized cyclo-... 

In a preliminary attempt to improve the catalytic properties of the cycloamyloses Bunting and Bender (1968) and, subsequently, Kice and Bender (1968) replaced, in separate experiments, both a primary and a secondary cyclohexaamylose hydroxyl group with a thiol group which has a pKa closer to neutrality than a hydroxyl group. Unfortunately, neither derivative catalyzed the hydrolysis of m-nitrophenyl acetate to any greater extent than unmodified cyclohexaamylose. 

After the initial reaction subsides, the mixture is warmed to 80° until the evolution of hydrogen ceases (about 1 hr). After cooling, 8.4 gm (8.64 mmole) of cyclohexaamylose, dissolved in 10 ml of dimethyl sulfoxide, is added from a dropping funnel. 0.37 gm... 

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