Acyl hydrolysis

Imidazole, 4-acetyl-5-methyl-2-phenyl-synthesis, 5, 475 Imidazole, 1-acyl-reactions, 5, 452 rearrangement, 5, 379 Imidazole, 2-acyl-synthesis, 5, 392, 402, 408 Imidazole, 4-acyl-synthesis, 5, 468 Imidazole, C-acyl-UV spectra, 5, 356 Imidazole, N-acyl-hydrolysis rate constant, 5, 350 reactions, 5, 451-453 synthesis, 5, 54, 390-393 Imidazole, alkenyl-oxidation, 5, 437 polymerization, 5, 437 Imidazole, 1-alkoxycarbonyl-decarboxylation, 5, 453 Imidazole, 2-alkoxy-l-methyl-reactions, 5, 102 thermal rearrangement, 5, 443 Imidazole, 4-alkoxymethyl-synthesis, 5, 480 Imidazole, alkyl-oxidation, 5, 430 synthesis, 5, 484 UV spectra, 5, 355 Imidazole, 1-alkyl-alkylation, 5, 73 bromination, 5, 398, 399 HNMR, 5, 353 synthesis, 5, 383 thermal rearrangement, 5, 363 Imidazole, 2-alkyl-reactions, 5, 88 synthesis, 5, 469... 

A complex example of activation, aimed at improving ocular delivery, has been reported for prodrugs of pilocarpine (8.87, Fig. 8.6) [123][124], The prodrugs are, in fact, lipophilic diesters of pilocarpic acid (8.86, Fig. 8.6). The first step is enzymatic O-acyl hydrolysis to remove the acyl carrier (Fig. 8.6, Reaction a). In a second step, intramolecular nucleophilic attack leads to loss of the alcohol carrier and ring closure to pilocarpine (Fig. 8.6, Reaction b). 

If aspartic acid-52 acts as a nucleophile in lysozyme reactions a glycosyl enzyme intermediate will be formed [60]. There is no evidence, kinetic or otherwise, for substituted enzyme intermediates, but rapid breakdown might preclude attainment of detectable concentrations. Formation of a substituted enzyme could explain the observed retention of configuration at the anomeric carbon in transglycosidation reactions, provided backside attack in a subsequent reaction is chemically reasonable. It has therefore been important to attempt to understand the chemistry of acylal hydrolysis so as to assess the properties that would be expected of an acylal intermediate in reactions catalysed by the enzyme. 

A carbocation is strongly stabilized by an X substituent (Figure 7.1a) through a -type interaction which also involves partial delocalization of the nonbonded electron pair of X to the formally electron-deficient center. At the same time, the LUMO is elevated, reducing the reactivity of the electron-deficient center toward attack by nucleophiles. The effects of substitution are cumulative. Thus, the more X -type substituents there are, the more thermodynamically stable is the cation and the less reactive it is as a Lewis acid. As an extreme example, guanidinium ion, which may be written as [C(NH2)3]+, is stable in water. Species of the type [— ( ) ]1 are common intermediates in acyl hydrolysis reactions. Even cations stabilized by fluorine have been reported and recently studied theoretically [127]. 

Aminoketones can also be made from amino acids by successive acylation-hydrolysis steps. 

The results of these studies are in agreement with the acylation/hydrolysis studies reported for delphisine. ... 

Esters with one or two fluorines at the a-carbon are useful building blocks for construction of interesting and novel biologically active substrates. Alkylation of a-fluorocarboethoxy phosphonium ylides followed by hydrolysis of the resultant phosphonium salt with 5% aqueous sodium bicarbonate provides a useful preparative route to a-fluoroesters. Similarly, acylation/hydrolysis of either a-fluoro phosphonium ylides or a-fluorophosphonate anions gives a general route to 2-fluoro-3-oxo-esters. The a,a-difluoroesters can be prepared by Cu° catalyzed addition of iododifluoroacetates to olefins followed by reduction of the iodo addition adduct. Both terminal and internal olefins participate equally well in the addition reaction. 

Preparation of 2-Fluoro-3-Oxoalkanoates Via Acylation-Hydrolysis of Ylides... 

Several routes to this class of compounds have been reported, such as (a) crossed Claisen condensation reactions (50-53) (b) acylation of the anion derived from ethyl fluoroacetate (54) or self-condensation of the anion derived from ethyl bromofluoroacetate (55) (c) electrophilic fluorination of the anion of p-ketoesters (56,57) (d) acylation-hydrolysis of fluoroolefins (58) and (e) acylation of fluorine-containing ketene silyl acetals (Easdon, J.C., University of Iowa, unpublished data). The limitations associated with these methods and the success achieved in the alkylation-hydrolysis of a-fluoro phosphorus ylides prompted us to examine acylation-hydrolysis of these a-fluoro ylides as a general route to 2-fluoro-3-oxoesters. 

As noted earlier in the alkylation study of a-fluoro phosphorus ylides, hydrolysis of the resultant a-fluoro phosphonium salts and a-fluorophosphonates do not necessarily parallel each other. This difference is again exhibited in the hydrolysis of the acylated products of the a-fluoro ylides. For example, the acylation product (10) is readily hydrolyzed at room temperature to give the desired a-fluoro-p-ketoester. The results of the acylation-hydrolysis of (4) with a variety of alkyl, cycloalkyl and aryl acyl halides are summarized in Table HI. 

In contrast to the straightforward facile acylation-hydrolysis reaction of the a-fluoro phosphonium ylide, the acylated product from the a-fluoro phosphonate carbanion is cleaved by base in two different ways. When R is a hydrocarbon group, such as CH3 or C5H5CH2, attack at the acyl carbon with bases, such as sodium bicarbonate, sodium carbonate, sodium hydroxide, and potassium silanoate is favored (Path II in equation 13) with resultant elimination of the a-fluorophosphonate anion. Less than 10% of the desired 2-fluoro-3-oxoester is observed. However, when R is a halofluoroalkyl group (CF3, CF2CI, C3F7), attack of the base (aqueous sodium bicarbonate) occurs only at phosphorus (Path I in equation 13) and the 2-fluoro-3-... 

Therefore, when R is a hydrocarbon group, the acylation-hydrolysis of (4) is the preferred route. When R is perfluoroalkyl or halofluoroalkyl, the acylation-hydrolysis of (3) is the preferred route. Thus, by proper choice of the a-fluoro phosphorus ylide, the acylation-hydrolysis methodology provide a facile entry to a wide variety of a-fluoro-p-ketoesters from readily available precursors. 

N-Acetylneuraminic acid aldolase, use in fluorinated sugar synthesis, 158,161/ Acylation-hydrolysis of ylides, 2-fluoro-2-oxoalkanoate synthesis, 96-100 Acyl hypofluorites applications, 58 applications for shorter chain homologues, 60,61/ chemistry, 58—61... 

Ligands closely related to orthophosphate esters include acetylphosphate, acetylphenylphosphate and fluorophosphate. Alkaline hydrolysis of [Co OP(0)20COMe (NH3)5] occurs exclusively at the carbonyl centre, and the acceleration provided by cobalt(III) four atoms removed is minimal (10 times, equation This is a good comparative example of phosphoryl versus acyl hydrolysis,... 

Mixed esters are hydrolyzed by methods similar to those used for hydrolyzing cellulose triacetate. The hydrolysis eliminates small amounts of the combined sulfate ester, which, if not removed, affects thermal stability. Sulfuric acid is the preferred catalyst for hydrolysis since it is already present in the esterification mixture. On a large scale, partial neutralization of the catalyst may be necessary before hydrolysis. Increasing the amount of water during hydrolysis reduces the rates of viscosity reduction and acyl hydrolysis of cellulose acetate propionate and acetate butyrate esters (46). Several methods of hydrolyzing cellulose esters... 

A method that has been successfully applied to the resolution of p-amino acids is N-acylation or N-acyl hydrolysis. Enantioselective N-acylation of p-amino esters in an organic solvent has been carried out using Candida antarctica lipase A (CAL-A) lipase, while enantioselective hydrolysis of N-acyl p-amino acids in aqueous medium has been catalyzed by aminoacylase (Scheme 14.2). 

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