Deacylation reactions, catalyzed with

An enzyme reaction intermediate (Enz—O—C(0)R or Enz—S—C(O)R), formed by a carboxyl group transfer (e.g., from a peptide bond or ester) to a hydroxyl or thiol group of an active-site amino acyl residue of the enzyme. Such intermediates are formed in reactions catalyzed by serine proteases transglutaminase, and formylglyci-namide ribonucleotide amidotransferase . Acyl-enzyme intermediates often can be isolated at low temperatures, low pH, or a combination of both. For acyl-seryl derivatives, deacylation at a pH value of 2 is about 10 -fold slower than at the optimal pH. A primary isotope effect can frequently be observed with a C-labeled substrate. If an amide substrate is used, it is possible that a secondary isotope effect may be observed as welF. See also Active Site Titration Serpins (Inhibitory Mechanism)... 

The consecutive formation of o-hydroxybenzophenone (Figure 3) occurred by Fries transposition over phenylbenzoate. In the Fries reaction catalyzed by Lewis-type systems, aimed at the synthesis of hydroxyarylketones starting from aryl esters, the mechanism can be either (i) intermolecular, in which the benzoyl cation acylates phenylbenzoate with formation of benzoylphenylbenzoate, while the Ph-O-AfCL complex generates phenol (in this case, hydroxybenzophenone is a consecutive product of phenylbenzoate transformation), or (ii) intramolecular, in which phenylbenzoate directly transforms into hydroxybenzophenone, or (iii) again intermolecular, in which however the benzoyl cation acylates the Ph-O-AfCL complex, with formation of another complex which then decomposes to yield hydroxybenzophenone (mechanism of monomolecular deacylation-acylation). Mechanisms (i) and (iii) lead preferentially to the formation of p-hydroxybenzophenone (especially at low temperature), while mechanism (ii) to the ortho isomer. In the case of the Bronsted-type catalysis with zeolites, shape-selectivity effects may favor the formation of the para isomer with respect to the ortho one (11,12). 

In discussing possible mechanisms for the reactions catalyzed by E. coli glutaminase in Section I, it was concluded that either a two-step acylation-deacylation pathway or a one-step route, displacement by the ultimate nucleophile, could be accommodated by the results. It may be noted that any single displacement mechanism for a group transfer reaction requires that both incoming and outgoing substituent groups associate with the enzyme at the same time... 

Activation reactions catalyzed by serine proteases (including kallikreins) are an example of limited proteolysis in which the hydrolysis is limited to one or two particular peptide bonds. Hydrolysis of peptide bonds starts with the oxygen atom of the hydroxyl group of the serine residue that attacks the carbonyl carbon atom of the susceptible peptide bond. At the same time, the serine transfers a proton first to the histidine residue of the catalytic triad and then to the nitrogen atom of the susceptible peptide bond, which is then cleaved and released. The other part of the substrate is now covalently bound to the serine by an ester bond. The charge that develops at this stage is partially neutralized by the third (asparate) residue of the catalytic triad. This process is followed by deacylation, in which the histidine draws a... 

The condensation of unsymmetrical 1,3-diketones 14 (R = Me, R2 = C02Et, Ph) with phenyl- and p-tolylhydrazines in a solventless reaction catalyzed by sulfuric acid afforded mixtures of the two regioisomers 15 and 16, generally in good to excellent yields. However, reactions of 1-phenylbutane-l,3-dione with acylhydrazines led to 4,5-dihydro-5-hydroxypyrazole derivatives 17 with complete regioselectivity. These compounds were then thermally dehydrated and deacylated (R = Ph) in the presence of a catalytic amount of sulfuric acid. 

Then a new peptide bond is formed by the transfer of the carboxyl group of peptidyl-tRNA to the adjacent amino group of newly bound aminoacyl-tRNA. The resulting ribosome possesses a deacylated tRNA in its P site, and a peptidyl-tRNA, having a chain one amino acid longer, in its A site. EF-G catalyzes the translocation of peptidyl-tRNA from the A site to the P site with concomitant release of deacylated tRNA from the P site and the movement of mRNA by a three-nucleotide distance on the 30S ribosomal subunit. One mole of GTP is hydrolyzed in the translocation reaction catalyzed by EF-G. The net result of the above sequences of reactions is the elongation of one peptide bond at the expense of two molecules of GTP. 

DKR of secondary alcohol is achieved by coupling enzyme-catalyzed resolution with metal-catalyzed racemization. For efficient DKR, these catalyhc reactions must be compatible with each other. In the case of DKR of secondary alcohol with the lipase-ruthenium combinahon, the use of a proper acyl donor (required for enzymatic reaction) is parhcularly crucial because metal catalyst can react with the acyl donor or its deacylated form. Popular vinyl acetate is incompatible with all the ruthenium complexes, while isopropenyl acetate can be used with most monomeric ruthenium complexes. p-Chlorophenyl acetate (PCPA) is the best acyl donor for use with dimeric ruthenium complex 1. On the other hand, reaction temperature is another crucial factor. Many enzymes lose their activities at elevated temperatures. Thus, the racemizahon catalyst should show good catalytic efficiency at room temperature to be combined with these enzymes. One representative example is subtilisin. This enzyme rapidly loses catalytic activities at elevated temperatures and gradually even at ambient temperature. It therefore is compatible with the racemization catalysts 6-9, showing good activities at ambient temperature. In case the racemization catalyst requires an elevated temperature, CALB is the best counterpart. 

In lipase-catalyzed ROP, it is generally accepted that the monomer activation proceeds via the formation of an acyl-enzyme intermediate by reaction of the Ser residue with the lactone, rendering the carbonyl more prone to nucleophilic attack (Fig. 3) [60-64, 94]. Initiation of the polymerization occurs by deacylation of the acyl-enzyme intermediate by an appropriate nucleophile such as water or an alcohol to produce the corresponding co-hydroxycarboxylic acid or ester. Propagation, on the other hand, occurs by deacylation of the acyl-enzyme intermediate by the terminal hydroxyl group of the growing polymer chain to produce a polymer chain that is elongated by one monomer unit. 

The self-condensation of 1,3-dicarbonyl compounds provides a useful route to 4-hydroxy-pyran-2-ones and is catalyzed by acids or bases. Alcohol is continuously removed during the reaction. Amongst a number of examples, mention can be made of the detailed procedure for the synthesis of 3-acetyl-4-hydroxy-6-methylpyran-2-one (dehydroacetic acid) (550SC(3)23l) and the formation of the cyclopentyl derivative (321) (64RTC39). Deacylation at C-3 can generally be achieved on heating with acid. 

It has been suggested (70) that NAD acts by facilitating deacylation of the thiol ester, and the later kinetic studies (189) are in agreement with this view. Only NAD analogs which are active in the oxidative phosphorylation reaction will substitute for NAD in the enzyme-catalyzed arsenolysis of DPGA (188) or acetyl phosphate (SO). At higher pH (8.6) an irreversible S to N transfer of acetyl groups occurs. 

It has been reported that the distannoxanes can also promote transformation of the carbonyl function, e.g. esterification [333b], lactonization [340a], polymerization [340 b, c], acetahzation [341], deacetalization [342], and desilylation [342] as well as transesterification, and in each reaction the mild conditions enable survival of a variety of acid-labile functions. With recourse to organotin-catalyzed transesterification, a variant of deacylation can be performed under mild conditions while conventional deacylation demands acidic or basic conditions. When l,n-diol diacetate was treated... 

More recently, a biocatalytic manufacturing route was developed in which deacylation was accomplished by penicillin G acylase in water at room temperature, requiring no protection and deprotection (Scheme 8.9) [58]. Moreover, through reaction engineering, penicillin G acylase also catalyzes the acylation of 6-APA with either amino esters or aminoamides to produce a wide range of semi-synthetic P-lactam antibiotics such as amoxicillin and ampicillin. A similar approach could be applied to the synthesis of the 7-ADCA derivatives cefaclor, cephalexin, and cefadroxil. 

HMG-CoA reductase catalyzes the reductive deacylation of its substrate to mevalonate and coenzyme A in a 2-step reaction with a stoichiometry of 2 moles of NADPH oxidized per mole of product formed. 

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