Cyclodextrins bimolecular reactions

In cases where the natural amino acid side chains of enzymes are insufficient to carry out a desired reaction, the enzyme frequently uses coenzymes. A coenzyme is bound by the enzyme along with the substrate, and the enzyme catalyses the bimolecular reaction between the coenzyme and the substrate (cf. Section 2.6.3). A simple model for a-amino acid synthesis by transamination was developed by substituting /I-cyclodextrin with pyridoxamine. Pyridoxamine is able to carry out the transformation of a-keto acids to a-amino acids even without the presence of the cyclodextrin, but with the cyclodextrin cavity as well, the enzyme model proves to be more selective and transaminates substrates with aryl rings bound strongly by the cyclodextrin much more rapidly than those having little affinity for the cyclodextrin. Thus (p-le/f-butylphenyl) pyruvic acid and phenylpyruvic acid are transaminated respectively 15 000 and 100 times faster then pyruvic acid itself, to give (p-le/f-butylphenyl) alanine and phenylalanine (Scheme 12.5). 

Another attempt to use the host-guest complexation of simple cyclophanes has been reported by Schneider They take the easily accessible host 7, an analogue of which had been demonstrated by Koga to bind aromatic guest molecules by inclusion into its molecular cavity, and study its rate effects on nucleophilic aliphatic substitutions of ambident anions (NOf, CN, SCN ) on 2-bromomethylnaphthalene 8 and benzylbromide. Similar bimolecular reactions are well known in cyclodextrin chemistry and other artificial host systems . In addition to the rather poor accelerations observed (see Table 3) the product ratio is changed in the case of nitrite favouring attack of the ambident nucleophile via its nitrogen atom. 

In order to develop catalytic effects of cyclodextrins for bimolecular reactions, it needs to include two guest molecules simultaneously in a cyclodextrin (CD) cavity. Several examples of cyclodextrin-catalyzed bimolecular reactions have been reported. Rideout and Breslow have found that Diels-Alder reactions of cyclo-pentadiene with butenone, cyclopentadiene with acrylonitrile, and anthracene-9-carbinol with N-ethylmaleimide in water are markedly accelerated by 3-cyclodextrin (3-CD) (1). Komiyama and Hirai have reported site-selective Reimer-Tiemann reactions of phenols in cyclodextrin solutions (2). In most of these reactions, however, each substrate molecule is relatively small so that a 3-CD cavity may include simultaneously an additional reactant molecules. We found previously that the fluorescence quenching of pyrene and naphthalene by trimethylamine (TMA) or dimethylamine (DMA) in water is catalyzed by g-CD (3) Since the pyrene molecule is too large to be incorporated completely in the 3-CD cavity, it has been assumed that pyrene binds to a rim of the CD cavity to form a pyrene-capped CD complex and a remain-... 

We have also examined the use of cyclodextrin-derived artificial enzymes in promoting bimolecular aldol reactions, specifically those of m-nitrobenzaldehyde (57) and ofp-t-butylbenzaldehyde (58) with acetone [141]. Here, we examined a group of mono-substituted cyclodextrins as catalysts (e.g. 59), as well as two disubstituted (3-cyclodextrins (e.g. 60) (10 catalysts in all). They all bound the aldehyde components in the cyclodextrin cavity and used amino groups of the substituents to convert the acetone into its enamine. An intracomplex reaction with 58 and hydrolysis of the enamine product then afforded hydroxyketone 61 (cf. 62). These catalysts imitate natural enzymes classified as Class I aldolases. 

Intramolecular versions of the aqueous Diels-Alder reactions have also been investigated, though not to the same extent as with their bimolecular counterparts. However, since intramolecular reactions often exhibit considerable rate enhancements due to lowering of the entropy of activation, and the unique conformational aspects of the (necessarily cyclic) transition state can result in enhanced selectivities, it is not always clear what effect water has on a particular intramolecular Diels-Alder process. The situation is often complicated by the routine addition of p-cyclodextrin to the reaction medium. Blokzijl and Engberts have reported quantitative data on the intramolecular cycloadditions of substrates 6.1 in water and various solvents as a function of substituent R [71]. 

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