Transfer reactions, acyl

Glutaminase also catalyzes acyl transfer from glutamic acid to methanol by the reverse of the reaction of methyl glutamate hydrolysis (7)  

The rate constant = VN/ (CHaOH) (Eo) is 0.47 M1 sec-1 at 25° and pH 5.0, a value which may be compared to that for the virtual hydrolysis of glutamic acid fc0/(H20) of 91.5 M 1 sec1. Thus, from the ratio kK (H2O)/fc0J it is seen that the rate with methanol is some 194 times slower on a molar basis than that with water even though methanol is generally observed to be a somewhat better nucleophile than water in similar nonenzymic substitution reactions (14)- These results indicate that the enzyme shows a large preference kinetically for water over hydroxylamine or methanol compared to what would be expected on the basis of the intrinsic reactivities of these substances. 

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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 ... 

When a Br nsted base functions catalytically by sharing an electron pair with a proton, it is acting as a general base catalyst, but when it shares the electron with an atom other than the proton it is (by definition) acting as a nucleophile. This other atom (electrophilic site) is usually carbon, but in organic chemistry it might also be, for example, phosphorus or silicon, whereas in inorganic chemistry it could be the central metal ion in a coordination complex. Here we consider nucleophilic reactions at unsaturated carbon, primarily at carbonyl carbon. Nucleophilic reactions of carboxylic acid derivatives have been well studied. These acyl transfer reactions can be represented by... 

The only definite examples are the acyl transfer reactions of acylcorrinoids, discovered by Bernhauer and Irion 14), and later studied in more detail by Yamada et al. 180). These reactions can be written... 

Considerable effort into ntilising the Lewis basic properties of NHCs to catalyse acyl transfer reactions has been made as noted in Section 12.2.4.1. This concept has been extended to the use of enantiomerically pure NHCs to facilitate asymmetric... 

Thus, the family of azolides represents a versatile system of reagents with graduated reactivity, as will be shown in the following section by a comparison of kinetic data. Subsequent chapters will then demonstrate that this reactivity gradation is found as well for alcoholysis to esters, aminolysis to amides and peptides, hydrazinolysis, and a great variety of other azolide reactions. The preparative value of azolides is not limited to these acyl-transfer reactions, however. For example, azolides offer new synthetic routes to aldehydes and ketones via carboxylic acid azolides. In all these reactions it is of special value that the transformation of carboxylic acids to their azolides is achieved very easily in most cases the azolides need not even be isolated (Chapter 2). 

Aside from being fundamentally interesting and industrially important, phosphoryl and acyl transfer reactions are key biological processes. Numerous enzymes con-... 

Acyl-transfer reactions are some of the most important conversions in organic chemistry and biochemistry. Recent work has shown that adjacent cationic groups can also activate amides in acyl-transfer reactions. Friedel-Crafts acylations are known to proceed well with carboxylic acids, acid chlorides (and other halides), and acid anhydrides, but there are virtually no examples of acylations with simple amides.19 During studies related to unsaturated amides, we observed a cyclization reaction that is essentially an intramolecular acyl-transfer reaction involving an amide (eq 15). The indanone product is formed by a cyclization involving the dicationic species (40). To examine this further, the related amides 41 and 42 were studied in superacid promoted conversions (eqs 16-17). It was found that amide 42 leads to the indanone product while 41... 

Besides the intramolecular acyl-transfer reactions, electrophilic activation is shown to occur with intermolecular Friedel-Craft-type reactions.18 When the simple amides (45a,b) are reacted in the presence of superacid, the monoprotonated species (46a,b) is unreactive towards benzene (eq 18). Although in the case of 45b a trace amount of benzophenone is detected as a product, more than 95% of the starting amides 45a,b are isolated upon workup. In contrast, amides 47 and 48 give the acyl-transfer products in good yields (eqs 19-20). It was proposed that dications 49-50 are formed in the superacidic solution. The results indicate that protonated amino-groups can activate the adjacent (protonated) amide-groups in acyl-transfer reactions. 

Allosteric behavior of the heterotropic variety is seen in the interaction between polymer and detergent or polymer and polymer (Shirahama, 1974 Arai et al., 1973 Tsuchida and Osada, 1973). Shinkai et al. (1977b) observed a sigmoid profile of rate constant vs. concentration of cationic detergents in the acyl transfer reaction from p-nitrophenyl acetate (PNPA) to copolymers (7). 

This section describes the nucleophilic reactions—acyl transfer reactions mostly—promoted by micelles and polysoaps. The nucleophiles are imidazoles, oxyanions and thiols, the same catalytic groups found ubiquitously in the enzyme active site. These nucleophiles are remarkably activated in the anionic form in the presence of cationic micelles and cationic polysoaps. These results are explained by the concept of the hydrophobic ion pair (Kunitake et al.,... 

The importance of minimizing the number of covalent steps in the process to be catalysed is rather obvious. Single-step and double-step processes dominate the abzyme scene. However, there is substantial evidence that some acyl transfer reactions involve covalent antibody intermediates and so must proceed by up to four covalent steps. Nonetheless, such antibodies were not elicited by intentional design but rather discovered as a consequence of efficient screening for reactivity (Section 5). 

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. 

G. M. Blackburn, J. D. Plackett, Strain Effects in Acyl Transfer Reactions. Part I. The Kinetics of Hydrolysis of Some N-Aryl-Lactams , J. Chem. Soc., Perkin Trans. 2 1972, 1366-1371. 

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

Many examples of catalytic nucleic acids obtained by in vitro selection demonstrate that reactions catalyzed by ribozymes are not restricted to phosphodiester chemistry. Some of these ribozymes have activities that are highly relevant for theories of the origin of life. Hager et al. have outlined five roles for RNA to be verified experimentally to show that this transition could have occurred during evolution [127]. Four of these RNA functionalities have already been proven Its ability to specifically complex amino acids [128-132], its ability to catalyze RNA aminoacylation [106, 123, 133], acyl-transfer reactions [76, 86], amide-bond formation [76,77], and peptidyl transfer [65,66]. The remaining reaction, amino acid activation has not been demonstrated so far. 

The central role aminoacylated RNAs play in translation processes suggests that acyl transfer reactions catalyzed by RNA might have facilitated the devel-... 

Once the human body has a supply of pantothenic acid, it can add the remaining parts to create the intact molecule. The business part of coenzyme A is a terminal sulfhydryl (—SH) group. It is here that acyl (e.g., the acetyl group, —COCH3) groups are attached in the process of acyl transfer reactions. There are a large number of such reactions in human metabolism and they are concerned with all aspects of... 

Base-catalyzed acyl transfer reaction that converts a-acyloxyketones to (3-diketones. 

Amine, Alcohol and Phosphine Catalysts for Acyl Transfer Reactions... 

The preparation of stereochemically-enriched compounds by asymmetric acyl transfer using chiral nucleophihc catalysts has received significant attention in recent years [1-8]. One of the most synthetically useful and probably the most studied acyl transfer reaction to date is the kinetic resolution (KR) of ec-alcohols, a class of molecules which are important building blocks for the synthesis of a plethora of natural products, chiral ligands, auxiliaries, catalysts and biologically active compounds. This research area has been in the forefront of the contemporary organocatalysis renaissance [9, 10], and has resulted in a number of attractive and practical KR protocols. 

In general, catalytic asymmetric acyl transfer reactions can be classified into two main types depending on the nature of the nucleophile and the acyl donor (Scheme 2) [2]. 

Spivey AC, McDaid P (2007) Asymmetric acyl transfer reactions. In Dalko P (ed) Handbook of asymmetric organocatalysis. Wiley, Weinheim, pp 287-329... 

Metabolic derivatives of pantothenic acid are of fundamental importance in acyl transfer reactions and in condensation reactions requiring an acidic a-proton. The... 

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