Modification Reactions of Cyclodextrins

Modification Reactions of Cyclodextrins and the Chemistry of Modified Cyclodextrins 

The classic chemistry of native CyDs is now a kind of completed area, described in a book [1] and several reviews that summarize state-of-the-art syntheses of these macrocycles [2-4], while syntheses of several novel CyD structures or their analogues are given in the literature [5-8). Studies of CyDs as enzyme models, involving syntheses of numerous selectively substituted derivatives, have been reviewed [9-11]. Numerous journals and proceedings can also be mentioned here [12, 13). 

The first part of this chapter describes methods for modifying CyDs in which the number and exact positions of substituents have been ascertained and where pure compounds with unambiguous structures have been obtained. 

When highly water-soluble CyD derivatives are investigated for application in drug formulations, random modifications of hydroxyl groups to hydroxypropyl, sulfo-propyl, carboxymethyl, or silyl groups can be easily achieved [14]. On the other hand, if a supramolecular behavior is to be investigated using CyD derivatives, the 

Cyclodextrins and Their Complexes. Edited by Helena Dodziuk Copyright 2006 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 3-527-31280-3 

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Chemical modification of cyclodextrins is achieved through reactions of their hydroxyl groups. Of the 21 hydroxyls ofP-CD, the seven primary ones (C-6) can easily be reacted. In addition, the C-2 secondary hydroxyl groups are also fairly reactive while the ones at C-3 resist modification (e.g. by methylation). Several CD derivatives are available commercially in large quantities including -among others- randomly methylated P-cylodextrin and hydroxypropyl-P-cylodextrin [2]. Chemical modifications substantially alter the solubility of cyclodextrins in water. For example, the solubility of P-CD... 

The amide (38a) is photochemically inert on irradiation in ether. The related compound (38b) is, however, photochemically reactive and undergoes fission by a Norrish Type II process to yield a mixture of products.The results of a study of the enantioselective photodeconjugation reactions of the lactones (39) have been published. The behaviour of the ketones (40) and (41) in the isotropic and the two solid phases of heneicosane (CcxH ) has been evaluated. The influence of the various phases on the ratio of elimination to cyclization products of the ketones was discussed. The modification of the photoreactivity of ketones (42) in cyclodextrin has been... 

Whereas the majority of dendrimer-based lipophilic-hydrophilic inclusion phenomena discussed thus far results in random guest positioning on a branched framework, ordered interactions in supramolecular assemblies are also of interest. For example, Gonzalez et al. reported the surface modification of poIy(propyl-eneimine)s with cobaltocenium groups that are easily reduced to Co(0). Reaction of the amine termini with I-chlorooarbonylcobaltocenium afforded the metal-terminated dendrimers. The lipophilic, charge-neutral poly-cobaltocenes were rendered H2O soluble via addition of /1-cyclodextrin (36, fi-CD) based on its cylindrical... 

When subjected to the action of trimethylsilyl triflate and acetic anhydride, careful control of the reaction conditions leads to cyclodextrin 11 by selective replacement of the ben2yl groups from the primary rim by acetates (Scheme 9.5) [19]. The position 3 can also be selectively deprotected by the action of triethylsilane and iodine at low temperature, giving access to cyclodextrin 12 bearing a functionahzation pattern similar to cyclodextrin 9a [20]. These reactions illustrate another approach toward the selective modification of cyclodextrins selective removal of already installed groups, which is the counterpart to the selective installation of functional groups. 

Dasarathu Reddy, G., Ramanathan, K. V., and Ramamurthy, V., Modification of photochemistry by cyclodextrin complexation competitive Norrish type 1 and type 11 reactions of benzoin alkyl ethers,/. Org. Chem., 51, 3085,1986. 

Variations of this method are possible in several ways. First of all, cyclodextrin which is available on a large scale by enzymatically catalyzed modification of starch can be tailored by chemical reactions. Furthermore, copolymerizations between different host-guest complexes are possible whereby in some cases the reactivity ratios differ from those reported in literature. 

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