Acylation, Deacylation

Diethyl aminomethylenemalonate (13) was A-acylated with acetic anhydride (75JHC1245). 

Diethyl N-(2-Aminophenyl)aminomethylenemalonate was acetylated by treatment with acetic anhydride at room temperature to give the 2-acetamido derivative (1493) in 78% yield (59MI1). 

The treatment of 5-pyrazolylaminomethylenemalonate (1494, R = H) with acetyl chloride in pyridine gave the 1-acetyl derivative (1494, R = Ac) in 66% yield (74AP177). 

The reaction of 7V-(6-amino-4-pyrimidinyl)aminomethylenemalonates (1497, R1 = H) and acetic anhydride at reflux temperature overnight gave the 6-acetamido derivatives (1497, R1 = Ac) in 60-68% yields (72JOC3980). 

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A neat synthesis of 4-nitroindole depends on an acylation-deacylation sequence from 2-methyl-3-nitroaniline, as shown in Eq. 10.53.70 On the other hand, treatment of /V-protected indoles with acetyl nitrate generated in situ at low temperature gives the corresponding... 

Figure 5.4 Competing catalytic mechanisms of methanolysis of pNPOAc. Mechanism A thiol-mediated methanolysis via an acylation-deacylation cycle mechanism B direct delivery of complex-bound methoxide ion.

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... 

At present, mqor progress in efficiency is found in the case of the nucleophilic catal3rsis. Table 8—1 lists apparent rate constants of acylation, deacylation, and turnover available at near pH 8 in some nudeoplulic catalyses of fire PNPA hydrolysis, and these data ccnnpared with those for oKdiymotrypsin. PNPA was selected as standard substrate because of its wide use. It is noteworthy that substrate binding was not observed for any of the synthetic systems. 

This article reviews the main applications of glycosidases and lipases in the synthesis of glycosidic bonds and in acylation/deacylation reactions of carbohydrates, respectively. Special attention is given to the factors that can affect the selectivity of the reactions, such as the enzyme origin, the structure of the substrates, and the reaction medium. A number of reviews have appeared in the literature on enzymatic synthesis of carbohydrates that include reactions with glycosidases and/or lipases [ 1 - 6]. In this article only a selection of examples are given to illustrate the discussion, rather than an extensive compilation of the work published in the area. 

Non-enzymic Acylation, Deacylation and Migration. Traditionally, acetylation of a reducing sugar with acetic anhydride and fused sodium acetate gives predominantly the fully acetylated equatorial (usually p) pyranose, because of the greater acidity and nucleophilicity of the equatorial OH, whereas acid-catalysed acetylation gives the axial acetate, thermodynamically favoured by the anomeric elfect. 

For example, a superb mimic of the charge-relay system in serine proteases has been prepared by attaching both carboxylate and imidazole to a-, fi-, and y-CyDs [24]. The hydroxy group, the last component of the charge-relay system, is provided by the CyDs. The activity (kinetic parameters) of the -CyD-based artificial enzyme for ester hydrolysis is close to that of aartificial enzymes show acylation, deacylation, and turnover, as is observed in the reactions of chymo-trypsin. The substrate-specificity is dependent on the kind of CyD used, since it is primarily governed by the substrate-binding process. In phenyl ester hydrolysis, a- and yS-CyD-based artificial enzymes are better than the y-CyD-based artificial enzyme. For the hydrolysis of tryptophan ethyl ester, however, the y-CyD-based artificial enzyme is the best. In another serine protease model, tripeptide (Ser-His-Asp) is directly introduced to the primary hydroxyl side of f -CyD [25]. This... 

Figure 1. The overall mechanism of chymotrypsin, showing acylation, deacylation, and the acyl-enzyme intermediate.

Hydrolytic enzymes (lipases, proteases) for the regioselective acylation/ deacylation of carbohydrates... 

Figure 18.9 shows the pH-activity profiles of the native and complexed enzymes using BANA as the low molecular weight substrate. The complexed BT is found to have an appreciable retention of enzymatic activity. This finding indicates that one imidazolyl group (histidine), which cooperates with both COOH (aspartic acid) and OH (serine) in acylation-deacylation as an intermediate step in the enzyme catalytic action [22], is free of salt linkages with KPVS. 

Similar half-life-times (/1/2) of AA into gellan (A) and Ca-gellan (B) film networks were observed (Table 2), whereas acylated-deacylated gellan network led to the longest ti/2 at all RH studied, when the lower proportion of glycerol (C-films) was used, lag times included. Otherwise, AA showed the lowest ti/2 values into D-films stored at 57.7% and 75.2% RH (18.6 and 9.5 days, respectively), while the same ti/2 (75 days) was determined at 33.3% with respect to C-films (Table 2). It is then suggested that the water contents derived from equilibration above 33.3% RH may be more available for chemical reactions because it did... 

Early studies desalbe the transesterilication between an active ester and a nucleophile like water catalyzed by amino alcohols [37-46]. For the hydrolysis of active p-nitrophenyl acetates, amino alcohol catalysts served as models for the catalytic diad of serine proteases. Kinetic studies show that the hydrolysis catalyzed by an amino alcohol proceeds via an acylation-deacylation mechanism. 

Scheme 7.10 Acylation-deacylation mechanism for amino-alcohols...

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