Catalysis acyl transfers

Acyl transfer from an acid an hydride to an alcohol is a standard method for the prep aration of esters The reaction IS subject to catalysis by either acids (H2SO4) or bases (pyri dine)... 

Ester hydrolysis can also be promoted by nucleophilic catalysis. If a component of the reaction system is a more effective nucleophile toward the carbonyl group than hydroxide ion or water under a given set of conditions, an acyl-transfer reaction can take place to form an intermediate ... 

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... 

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

The CD-mediated cleavage of p-N02C6H4NHC0CF3 proceeds by acyl transfer to a-CD. Since the trifluoracetyl-CD, so produced, hydrolyses fairly quickly even at pFI7, the overall reaction shows true catalysis. Thus, for the reaction in (27), a-CD behaves as a model enzyme and shows three of the features of chymotrypsin (i) it provides a hydrophobic binding site (ii) it catalyses the loss of leaving group and (iii) the reaction proceeds through an acyl intermediate (Komiyama and Bender, 1977 Bender and Komiyama, 1978). 

Clearly, the oxyanion hole is now as significant a feature of the binding site of such acyl transfer abzymes as it is already for esterases and peptidases — and not without good reason. Knossow has analysed the structures of three esterase-like catalytic antibodies, each elicited in response to the same phosphonate TSA hapten (Charbonnier et al., 1997). Catalysis for all three is accounted for by transition state stabilization and in each case there is an... 

A similar bait and switch approach has been exploited for acyl-transfer reactions (Janda et al., 1990b, 1991c). The design of hapten [10] incorporates both a transition state mimic and the cationic pyridinium moiety, designed to induce the presence of a potential general acid/base or nucleophilic amino acid residue in the combining site, able to assist in catalysis of the hydrolysis of substrate [11] (Appendix entry 2.6). 

In 1991, Jacobs analysed 18 examples of antibody catalysis of acyl-transfer reactions as a test of the Pauling concept, i.e. delivering catalysis by TS stabilization. The range of examples included the hydrolysis of aryl carbonates and of both aryl and alkyl esters. In some cases more than one reaction was catalysed by the same antibody, in others the same reaction was catalysed by different antibodies. 

The Catalysis of Acyl-Transfer Reactions of Reactive Esters... 68... 

In the 1990s, short peptides,and other nucleophiles °° ° were used as organocatalysts for a number of enantioselective acyl transfer processes transformations that set the stage for the more recent research in the area of nucleophilic catalysis.One of the most appealing approaches to enantioselective acyl transfer was outlined by Fu using an azaferrocene catalyst (6) [Eq. (11.6)]. While these pyridyl systems are not organic catalysts in the strictest sense, these azaferrocene compounds function as chiral dimethylaminopyridine equivalents for a broad range of acyl transfer processes ... 

Oxygen-based nucleophiles can also be employed for the catalysis of acyl transfer. For example, pyridine-A-oxide derivatives such as 4-DMAP-A-oxide have long been known as such catalysts although, interestingly, these catalophores are reportedly particularly efficient at mediating sulfonyl and phosphoryl transfer [229-230]. 

Sanders and coworkers have extended the use of these cyclic porphyrin systems in the catalysis of acyl-transfer reactions [15] and hetero-Diels-Alder reactions [16]. 

Catalysis of Acyl Transfer Processes by Crown-Ether Supported Alkaline-Earth Metal Ions... 

Earlier work in this field has been thoroughly reviewed [1,2]. However, to illustrate in a sensible and logical way the evolution from simple metal ion promotion of acyl transfer in supramolecular complexes to supramolecular catalysts capable of turnover catalysis, an account of earlier work is appropriate. The following sections present a brief overview of our earlier observations related to the influence of alkaline-earth metal ions and their complexes with crown ethers on the alcoholysis of esters and of activated amides under basic conditions. 

The above types of catalysis function by stabilizing the transition state of the reaction without changing the mechanism. Catalysts may also involve a different reaction, pathway. A typical example is nucleophilic catalysis in an acyl transfer or hydrolytic reaction. The hydrolysis of acetic anhydride is greatly enhanced by pyridine because of the rapid formation of the highly reactive acetylpyridinium ion (equation 2.12). For nucleophilic catalysis to be efficient, the nucleophile... 

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