Acylation, mechanism

Similarly, the acylation mechanism also involves a two-stage reaction.23 Poly-phosphoric acid, A1C13, HF/BF3, and CF3S03H. are typical catalysts. 

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). 

The precise origin of the stereoselectivity in these reactions is not known at present. The acyl mechanism has generally been assumed, rather than the alkoxycarbonyl one (see Section 61.2.5.8) and it seems reasonable that asymmetric induction must have taken place prior to or during the CO insertion reaction. A review of asymmetric carbonylation is available.579... 

The lysozyme mechanism (Scheme 11.21) has an acylal intermediate with a decay step which is fast compared with its rate of formation, so it is not normally possible to observe the intermediate. The acylal mechanism has recently been established by modifying both enzyme and substrate so that the intermediate can be isolated in this case, the intermediate was stabilised so much that its X-ray crystallographic structure could be determined. Substrate A in Scheme 11.21 was employed [22 ] in which the 2 -fluoro substituent reduces the reactivity at the Cl position so that any acylal enzyme formed from this substrate would have a... 

Deacylation of l-AMN involves, most likely, the reverse steps of acetylation. The resulting acylium ions can react with 2-MN with formation of the 2-AMN isomer. However, the isomerization of 1-AMN into 2-AMN does not occur essentially through this deacylation-acylation mechanism, but through the following intermolecular transacylation process reaction ... 

Acylation Mechanisms of Electrophilic Aromatic Substitution (page 696) ElectrophilicAromatic Substitution Reactions (page 699)... 

The acyl cation reacts with benzene by a Friedel-Crafts acylation mechanism. 

The occurrence of the ionization mechanism (eqns. (6) and (18)) in preference to the alternative addition mechanism (eqn. (24)) has been demonstrated by a study of the initiating activities of the series of bases pyridine, a-picoline, 2,6-lutidine [21]. Mechanism (24) is analogous to the normal tertiary base-catalysed acylation mechanism encountered with anhydrides such as acetic anhydride [41]. Steric factors determine the... 

De-acylation Mechanism (produces free carboxylic acid) ... 

The acylation mechanism was assumed to consist of the four steps following ... 

Whilst the Friedel-Crafts acylation mechanism remains to be accurately determined (ref. 6) it is reasonable to postulate four stages. 

Three different mechanisms have been proposed [1] for the Fries rearrangement with AICI3 (i) an intramolecular mechanism with a direct acyl shift from the oxygen atom to a carbon atom of the ring (ii) a monomolecular deacylation-acylation mechanism with an acyl chloride intermediate and (iii) an intermolecular mechanism (transacylation). 

In an attempt to avoid problems with the phosphate groups from the CoA moiety, the penultimate intermediate in the synthesis of the bisubstrate inhibitor, A-bromoacetyltryptamine, was tested as a possible affinity label inhibitor or as a substrate for the in situ enzymatic synthesis of the bisubstrate inhibitor through an acylation mechanism. N-Bromoacetyltryptamine did act as an inhibitor of the enzyme, but inhibition could be reversed by dialysis suggesting that the inhibition was not due to a covalent adduct. It was shown that the enzyme catalyzed the acylation of A-bromoacetyltryptamine by CoASH to form compound 6a with a rate enhancement of 3.3 x 10 relative to the uncatalyzed reaction. Ultimately, it was shown that the acylation reaction occurs at the same active site as the acetylation activity. A closer inspection of the kinetics of inhibition by tbe bisubstrate analog 6a resulted in the observation of slow-onset inhibition over the first few minutes of the reaction with a A) value of 84nmol 1 . Owing to its neutrality, A-bromoacetyltryptamine was tested as an inhibitor in vivo. The analog precursor was shown to inhibit melatonin production in norepinephrine-stimulated pinealocytes in a concentration-dependent manner and with low cytotoxicity. 

Figure 11.14 Amino acylation mechanisms catalyzed by aminoacyl-tRNA synthetases The two classes of aminoacyl-tRNA synthetases (aRS s) differ in the site of aminoacylation. Class I aRS s aminoacylate 2 -OH whereas class 11 aRS s add amino acids to 3 -OH of the terminal ribose of the 3 -terminal CCA of cognate tRNA. Magnesinm ions complexed with ATP to enter the active site of aRS may play a dual role in the activation step by both stabilizing the conformation of the ATP (Mg ion bridges the P- and y-phosphates) and participating in adenylate formation (second Mg is found between a- and P-phosphates in some aRS s). In class I aRS, both Lys of MSK and His of HIGH stabilize the bipyramidal oxyphosphorane transition state while R of motif 2 in class II aRS participates in the stabilization of the putative pentacoordinate transition state. The resulting mixed anhydride aminoacyl adenylate is held by the enzyme for the next reaction, i.e. the attack by the 2 -OH (class I) or 3 -OH (class II) of the terminal adenosine at the carbonyl of the aminoacyl adenylate. The amino acid then becomes esterified to the cognate tRNA.

The sulfene is electrophilic in a slightly odd way the alcohol acts as a nucleophile for sulfur and generates an anion of carbon which undergoes a proton transfer to give the mesylate. It is not uncommon for anions to form adjacent to suifur, as you will see again in Chapter 27. Notice how similar the overall mechanism is to the acylation mechanism we showed you above. 

The ammonolysis of j3-thiolactones and other ring opening reactions proceed only by a sulfur-acyl ring opening mechanism, in contrast to the analogous reactions with j5-lactones where the ring opens by both alkyl and acyl mechanisms [19, 20]. 

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