Catalysis noncovalent

In many other catalyses by CyDs, these cyclic oUgonudeotides do not directly react with substrates. Direct proton-transfer between them does not occur either. In- 

CyDs merely offer their cavity as a hydrophobic and constrained reaction field. When substrate molecules are accommodated in the cavity, they take specific orientation there and thus two otherwise equivalent positions in these substrates can be clearly differentiated. Under these conditions, two reagents for bimolecular reactions are placed near each other with a specific mutual orientation. This situation is of course favorable for prompt and selective reactions. Other reactions are accelerated simply because the transition state is stabilized in the apolar cavity of CyD. Furthermore, the substrates and/or the products are protected from undesired side reactions (e.g. decomposition by other reagents). Therefore, notable specificity (regio-, stereo-, and enantio-selectivity), together with relatively high yields, are satisfactorily accomplished in CyD-catalyzed reactions. 

Although inferior results have been achieved when compared to promoter le, both catalysts lf,g could be recovered and reused up to five runs with little loss of efficiency. 

Experimental findings and a computational study supported a non-covalent general acid/base activation of the reagents in the epoxidation mediated by diaiyl prolinols, where the oxa-Michael addition of the nucleophilic peroxide is the rate- and stereoselectivity determining-step, followed by a fast ring-closure step to the epoxide. The most stable transition 

The epoxides were isolated in generally good to high yield, with moderate to excellent diastereo- and enantioselectivity. Some of these epoxides have been further elaborated to derivatives of synthetic or biological interest. 

2 Michael-type Additions and MIRC (Michael Initiated Ring Closure) Strategy 

The Michael addition is a fundamental process to form carbon-carbon and carbon-heteroatom bonds, with a plethora of asymmetric methods flourishing in the realm of organocatalysis.  

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In contrast to the reactions of the cycloamyloses with esters of carboxylic acids and organophosphorus compounds, the rate of an organic reaction may, in some cases, be modified simply by inclusion of the reactant within the cycloamylose cavity. Noncovalent catalysis may be attributed to either (1) a microsolvent effect derived from the relatively apolar properties of the microscopic cycloamylose cavity or (2) a conformational effect derived from the geometrical requirements of the inclusion process. Kinetically, noncovalent catalysis may be characterized in the same way as covalent catalysis that is, /c2 once again represents the rate of all productive processes that occur within the inclusion complex, and Kd represents the equilibrium constant for dissociation of the complex. 

The manifestation of noncovalent catalysis as a microsolvent effect is illustrated by cycloamylose-catalyzed decarboxylations of activated carboxylic acid anions. Anionic decarboxylations, as illustrated in scheme VII, are generally assumed to proceed by a rate-determining heterolytic... 

Kim SP, Leach AG, Honk KN. The origins of noncovalent catalysis of intermolecular Diels-Alder reactions by cyclodextrins, self-assembling capsules, antibodies, and RNAses. J. Org. Chem. 105. 2002 67(12) 4250-4260. 

Fig. 10.4 (continued) tide bond cleavage. In the cysteine (and also serine and threonine) proteases, the nucleophile is the protease type amino acid (in this case cysteine) which forms a covalent bond with the carbon atom of the bond to be cleaved (covalent catalysis) in contrast to the metalloprotei-nases and aspartic proteases which use an activated water molecule to attack the carbon atom to be cleaved (noncovalent catalysis). In covalent catalysis, a nearby histidine residue normally functions as a base to activate the mechanism, whereas in noncovalent catalysis, the protease type serves as an acid and base, with an ancillary histidine (aspartate proteases) or aspartate or glutamate residue acting as the nucleophile (Fig. 8.2b) (Modified from Fig. 9.18 in Berg., et al., Biochemistry, 5th Ed. 2002, W.H. Freeman Co., New York)...

A self-assembled coordination cage and micelles were found to accelerate Diels-Alder reactions in an aqueous media. The catalysis of Diels-Alder reactions via noncovalent binding by synthetic, protein, and nucleic acid hosts has been surveyed and compared to explore the origin of the noncovalent catalysis. These catalysts consist of binding cavities that form complexes containing both the diene with the dienophile and the reaction occurring in the cavity. The binding requires no formation of covalent bonds and is driven principally by the hydrophobic (or solvophobic) effect. ... 

Wittkopp, A. and Schreiner, PR. (2003) Metal-free, noncovalent catalysis of Diels-Alder reactions by neutral hydrogen bond donors in organic solvents and in water. Chemistry - A European Journal, 9, 407 14. 

A. Noncovalent catalysis. The catalytic steps that involve noncovalent interactions without forming covalent intermediates with the enzyme molecules. These include 1. Entropic effect Chemical catalysis in solution is slow because bringing together substrate and catalyst involves a considerable loss of entropy. The approximation and orientation of substrate within the confines of the enzyme-substrate complex in an enzymatic reaction circumvent the loss of translational or rotational entropy in the transition state. This advantage in entropy is compensated by the EA... 

The adducts were isolated in good yield and up to 75% ee. Experimental findings and DFT calculations were both consistent with noncovalent catalysis, highlighting the ability of diatyl prolinols to behave in a similar mode of action as previously attested by die pivotal work of Wynberg and coworkers in natural Cinchona alkaloid-catalysed Michael addition reactions. ... 

In many cases, the effectiveness of a short peptide catalysts relies on their bifunctional character, since the donor can be activated via enamine formation (covalent catalysis), and the acceptor - via hydrogen bonding with the NH group and/or the C-terminal carbo)yl group of peptide (noncovalent catalysis). Advantageously, peptides provide more hydrogen-bond donor sites than the constituent amino acids alone. 

Wittkopp, A. Schreiner, P. R. Metal-Free, Noncovalent Catalysis of Diels-Alder Reactions by Neutral Hydrogen Bond Donors in Organic Solvents and in Water. Chem. Eur. J. 2003, 9, 407-414. 

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