Catalysis non-covalent

In this form of catalysis, inclusion of the substrate in the CD cavity provides an environment for the reaction that is different from that of the bulk, normally aqueous, medium. In the traditional view, the catalytic effect arises from the less polar nature of the cavity (a microdielectric effect) and/or from the conformational restraints imposed on the substrate by the geometry of inclusion (Bender and Komiyama, 1978). However, catalysis may also arise as a result of differential solvation effects at the interface of the CD cavity with the exterior aqueous environment (Tee and Bennett, 1988a,b Tee, 1989). 

A simple example of non-covalent catalysis is the intramolecular acyl transfer [3] to [4] which is catalysed by a-CD but retarded by /3-CD (Griffiths and Bender, 1973). As seen by the constants in Table 1, the 

In another example of intramolecular participation, the attack of the carboxylate ion group of mono-p-carboxyphenyl esters of substituted glutaric acids, the rate of anhydride formation is sharply reduced by /3-CD (VanderJagt et al., 1970). Apparently, the substrates bind to /3-CD in a conformation that is unsuitable for reaction. At the same time, the large rate reductions must also mean that the transition state of the reaction cannot be bound by /3-CD in such a way as to be significantly stabilized. 

Several other intramolecular reactions showed only slight rate accelerations or retardations (VanderJagt et al., 1970). Of potential synthetic use, it has been found that both intramolecular and intermolecular Diels-Alder reactions can be catalysed by /3-CD (Sternbach and Rossana, 1982 Breslow and Guo, 1988). 

The rate of decarboxylation of activated carboxylate anions [e.g. (10)], shows strong solvent dependence. It is not surprising, therefore, that these reactions have been used to probe the microsolvent effects of micelles and CDs (Fendler and Fendler, 1975). In particular, it was anticipated that complexation with a CD might result in catalysis by providing an environment for the reaction that is less polar than water. 

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Finally, in the sense that the imposition of conformational restrictions or specific solvent effects on an organic molecule are forms of strain, non-covalent catalysis by the cycloamyloses may provide a simple model for the investigation of strain and distortion effects in enzymatic reactions. 

Table 1 Non-covalent catalysis of intramolecular acyl transfer [3]—> [4].°...

In many instances non-covalent catalysis relies on the formation of hydrogen-... 

Proteases are enzymes catalyzing the hydrolysis of peptide bonds. They form one of the largest enzyme families encoded by the human genome, with more than 500 active members. Based on the different catalytic mechanisms of substrate hydrolysis, these enzymes are divided into four major classes serine/threonine, cysteine, metallo, and aspartic proteases. In serine, cysteine, and threonine proteases, the nucleophile of the catalytic site is a side chain of an amino acid in the protease (covalent catalysis). In metallo and aspartic proteases, the nucleophile is a water molecule activated through the interaction with amino acid side chains in the catalytic site (non-covalent catalysis) (Gerhartz et al., 2002). 

All the reactions catalyzed by CyDs (and by their derivatives) proceed via their complexes with substrates, in which the chemical transformation takes place. This reaction scheme is exactly parallel to that employed by naturally occurring enzymes, and both high specificity and large reaction rates are primarily associated with this reaction scheme. Catalyses by CyDs are divided into three categories (1) covalent catalysis in which a covalent intermediate is first formed from CyD and substrate and this intermediate is converted to the final products in the following step, (2) general acid-base catalysis by OH groups, and (3) non-covalent catalysis in which CyDs participate in the reactions only in a noncovalent fashion without even proton-transfer processes. The number of papers on catalysis by CyDs has... 

Figure 1.2 Classification of organocatalysts into covalent and non-covalent catalysis.

Recently an expansion of the electrophile scope of the conjugate addition of sulfur nucleophiles has been reported by different groups. As depicted in Fig. 2.29 for selected examples, Cinchona-denwed catalysts 203 and 205 promote highly enantioselective additions to nitrooleflns [387] and a,p-unsaturated V-acylated oxazolidin-2-ones [388] through non-covalent catalysis. Especially interesting results the Michael reaction to P-substituted nitroacrylates catalyzed by chiral thio-... 

While the alcoholysis of anhydrides outlined above presumably proceeds via non-covalent catalysis, a range of chiral Lewis bases have been used for the desymmetrization of alcohol substrates using covalent strategies. As representative examples of this process, Birman utilized the isothiourea BTM 149 in an asymmetric synthesis of (—)-lobeline via desymmetrization of lobelanidine 167... 

Non-covalent catalysis Catalysis in which there are no covalent interactions between the catalyst and the reacting substrate during the reaction. See covalent catalysis. 

Mine [7] and Kelly [8] were the first to prepare synthetic equivalents of this bidentate motif, using biphenylene diols as catalysts. Shortly after Etter had studied the hydrogen bonding patterns in supramolecular assemblies of various carbonyl compounds [9, 10], Curran introduced diarylurea derivatives as further bidentate organocatalysts [11, 12]. This interplay between supramolecular chemistry and non-covalent catalysis has turned out to be very fruitful ever since [13-15]. Schreiner subsequently showed that thioureas are also potent organocatalysts, which offer several advantages compared to urea derivatives, e.g., better solubility [13, 16]. In a proof-of-principle study, thiourea derivative 1 (Fig. 1, right) was used to catalyze the Diels-Alder reaction shown in Scheme 1 [16]. 

Intramolecular Ring-Forming Reactions by Non-Covalent Catalysis... 

Non-Covalent Catalysis with Chiral Primary Amines... 

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