Cyclodextrins capped

A number of capped cyclodextrins which are able to bind a metal ion at one end of their cavity, together with an organic guest in the cavity, have been synthesized. Such species parallel in several respects the family of completely synthetic vaulted transition-metal complexes prepared by Busch and coworkers and already discussed in Chapter 3 (section 3.5). 

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)... 

Double Heck reaction, 42 494 Double layer interface, 30 223-225 Double nucleophilic displacement, capped cyclodextrin, 32 437 Double-pulse method, 38 31 Double recognition models, 32 451 52 Doublet mechanisms, 30 43, 45, 47 Drago parameters, 38 212 Drougard-Decrooq equation, 30 345, 356, 371 Dry evaporation, perovskite preparation, 36 246-247... 

Scheme 4. Conversion of benzophenone-capped cyclodextrin to dideoxy derivative.

Generally, separation of regioisomers of capped cyclodextrins is difficult. Only in limited ideal examples is each isomer easily separated through the column and purified by recrystallization or reprecipitation without any difficulty. The phenanthrenedisulfonate cap is a typical example of this kind (72). But usually column separation (even a very efficient HPLC column) is not very helpful. Regioselective capping is very important in these sense and from a mixture of regioisomers, the most abundant isomer is usually purified by careful and repeated reprecipitation. 

Another type of photoactive capped cyclodextrin, azobenzene-capped cyclodextrin, is also reported, but regioisomer distribution is not mentioned and their treatment does not seem quite satisfactory. See Yoshimura, H., Saka, H., and Osa, T., J. Am. Chem. Soc. 101, 2779 (1979) Chem. Lett. 841, 1007 (1979) Chem. Lett. p. 29 (1980). 

Our best combination of the flexible capped cyclodextrin with the well-fitting substrate p-nitrophenyl ester 10 gave an acceleration - relative to hydrolysis in the same medium - of over one-million fold, exceeding that achieved by chymotrypsin with p-nitrophenyl acetate [86]. An even better fitting substrate (11) afforded an acceleration of ca. 80 000 000-fold, and saw a 62-fold increase in enantioselectivity as well [87, 88]. This is an enantiomeric excess of 98.4%. 

Interesting results came from the study of the reaction rates of these flexibly capped cyclodextrins with ra-f-butylphenyl acetate and m-nitrophenyl acetate (9). The ra-f-butylphenyl acetate was bound more weakly to theN-methyl derivative by a factor of 2.3, even with a new hydrophobic floor. This was reasonable if the geometry of the system were such that the substrate could not penetrate now as deeply into the cavity as it normally does. The result is in contrast with the situation of adamantanecarboxylate, which does not penetrate completely the cavity in the first place. On the other hand, the reaction rate for acetyl transfer within the complex was increased by a factor of 9. This was also expected, since now the new, more shallow, binding geometry of the substrate was closer to the geometry required in the transition state for acetyl transfer, so there was a smaller potential well from which the substrate had to climb. 

The cyclodextrins also form channel-type complexes, in which the host molecules are stacked on top of each other, like coins in a row. For example, a-cyclodextrin (cyclohexaamylose) forms cage complexes with acetic, propionic, and butyric acids, but channel complexes with valeric and higher acids. Capped cyclodextrins are known. 

The effect of the hydrophobic cyclodextrin cavity of 7 was enhanced and the lifetime of the 7-oxygen adduct was prolonged to about 1 hr in the aqueous medium at —10 °C when a drop of benzene was dispersed in the aqueous medium of the deoxy-7 imidazole complex. The benzene was probably occluded in the cavity of the capping cyclodextrin However, the life-time decreased with temperature of the aqueous medium and the oxygen adduct was scarcely observed above 0 C. The steric and... 

A. Ueno, K. Takahashi, T. Osa, Photocontrol of catalytic activity of capped cyclodextrin, J. Chem. Soc., Chem. Commun., 1981, 94-95. 

Capping of one side of the torus with an apolar moiety enhances the binding ability of a cyclodextrin. This effect is attributable to the increase in the apolar nature of the cavity due to the capping by the apolar groups. For example, capped )8-cyclodextrin (la) binds sodium l-anilino 8-naphthalenesulfonate 24 times better than parent j8-cyclodextrin [5]. The binding ability of another capped -cyclodextrin (lb) changes on photoirradiation, since the conformation of )8-cyclodextrin is varied due to the cis-trans photoisomerization of the azobenzene moiety [6]. 

Capped cyclodextrin, I, is also very helpful for preparation of regionspecifically bifunctionalized cyclodextrin (VI) via successive Sjj2 reaction with X" and Y (7). Compounds of this type are important to mimic a variety of enzymes since they have a hydrophobic recognition site as well as a bifunctional catalytic site (X...Y) which is very often encountered in native enzyme mechanisms. 

Triple recognition model "duplex cyclodextrin", (VIII), is also successfully constructed from capped cyclodextrin (I)(8), which may accomodate two different guest molecules to interact with each other in the central catalytic site. 

Preparation of the future main chain occurred via activated PFP-ester chemistry, as discussed in Sect. 2. For this, PFPA was used as monomer in a RAFT polymerization. After removal of the thioester chain end by treatment with excess AIBN, the aminolysis using monoamine-functionalized fluorescent dye (Oregon Green Cadaverine) and prop-2-yn-l-amine and l-aminopropan-2-ol was conducted. Via an azide-alkyne 1,3-dipolar cycloaddition, an azide-capped cyclodextrin was attached onto the alkyne units along the main chain. As demonstrated in Scheme 10, the cyclodextrin moiety works as a supramolecular binding site for adamantyl residues. This supramolecular binding concept resulted ultimately in linear-g-(linear-hyperbranched) graft terpolymers. 

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