Carboxylate esters, hydrolysis

The use of a lipophilic zinc(II) macrocycle complex, 1-hexadecyl-1,4,7,10-tetraazacyclododecane, to catalyze hydrolysis of lipophilic esters, both phosphate and carboxy (425), links this Section to the previous Section. Here, and in studies of the catalysis of hydrolysis of 4-nitrophenyl acetate by the Zn2+ and Co2+ complexes of tris(4,5-di-n-propyl-2 -imidazolyl)phosphine (426) and of a phosphate triester, a phos-phonate diester, and O-isopropyl methylfluorophosphonate (Sarin) by [Cu(A(A(A/,-trimethyl-A/,-tetradecylethylenediamine)l (427), various micellar effects have been brought into play. Catalysis of carboxylic ester hydrolysis is more effectively catalyzed by A"-methylimidazole-functionalized gold nanoparticles than by micellar catalysis (428). Other reports on mechanisms of metal-assisted carboxy ester hydrolyses deal with copper(II) (429), zinc(II) (430,431), and palladium(II) (432). 

Fig. 5. Reaction mechanism for carboxyl ester hydrolysis by chymotrypsin.

Carboxylic Ester Hydrolysis Butyl Benzyl Phthalate... 

Of the mechanisms of carboxylic ester hydrolysis, that for the base-catalyzed reaction is the best understood. It generally proceeds by bimolecular attack of hydroxide ion on the carbonyl group, forming a tetrahedral intermediate, followed by elimination with acyl-oxygen fission ... 

Because of the relative simplicity of carboxylic ester hydrolysis, in general, and that of base catalyzed ester hydrolysis, in particular, these reactions have served well as model systems in investigations of micellar effects on reaction rates and activation parameters. In addition, the prevalence in biological systems of carboxylic ester hydrolyses catalyzed by nucleophiles and by enzymes renders the investigation of micelle-catalyzed ester hydrolyses of obvious importance. 

The completely uncatalysed reaction involves nucleophilic attack by the OH group on the P=0 bond to form a five-covalent intermediate much like the tetrahedral intermediate in carboxylate ester hydrolysis. There is a difference. Phosphorus prefers five-membered rings to any other... 

S)-Naproxen Kinetic resolution by carboxylic ester hydrolysis (recombinant esterase) Development stage Chirotech Sha-sun Chemicals, India [14]... 

Again by analogy with peptide hydrolysis, metalloenzymes catalyzing ester hydrolysis may take advantage of additional chemical features provided by amino-acid residues present in the active-site cavity. This situation occurs with car-boxypeptidase, " which shows esterase activity in vitro. Although the rate-limiting steps for carboxylic esters and peptides may differ, several features, such as the pH dependences of cat and and the presence of two spectroscopically observable intermediates, point to substantially similar mechanisms. On the other hand, carboxylic ester hydrolysis catalyzed by carbonic anhydrase seems to rely on fewer additional features of the active-site cavity, perhaps only on the presence of a metal-coordinated hydroxide that can perform the nucleophilic attack on the carbonyl carbon atom." ... 

Day JNE, Ingold CK (1941) Mechanism and kinetics of carboxylic ester hydrolysis and carboxyl esterification. Trans Faraday Soc 37 686-705... 

Most transition states involve charged intermediates, which are stabilized within the active site of an enzyme via ionic bonds in pockets or holes bearing a matching opposite charge. Such charges are derived from acidic or basic amino acid side chains (such as Lys, Arg, Asp, or Glu) ° or are provided by (Lewis acid-type) metal ions, typically Zn +. Computer simulations studies suggested that in enzymes electrostatic effects provide the largest contribution to catalysis [107]. As a prominent example, the tetrahedral intermediate of carboxyl ester hydrolysis is stabilized in serine hydrolases by the so-called oxyanion hole (Scheme 2.1). 

Many enzymes form covalent bonds with their substrates during catalysis, such as the acyl-enzyme intermediate in carboxyl ester hydrolysis (Scheme 2.1) or the glycol monoester intermediate in epoxide hydrolysis (Scheme 2.85). Despite the covalent enzyme-substrate bond, such species are metastable and should be regarded as activated intermediates . Some enzymes utilize cofactors, such as... 

NucleophiUc substitution at carbonyl carbon, takes place in bimolecu-lar carboxylic ester hydrolysis with acyl-oxygen fission (21) by the... 

Nitriles are easily hydrolysed to the corresponding carboxylic acid, and 2-cyanochromone (chromone-2-carbonitrile) undergoes this transformation when heated with sulphuric acid [113], but the yield has not been published since the best route to a 2-cyanochromone [57] begins with the chromone-2-carboxylic ester, hydrolysis of nitriles cannot at present be considered a useful method of preparing chromone-2-carboxylic acids. 

Our continued search for better alternatives to traditional saponification procedures led to the use of tetraalkylammonium hydroxides. Tetraalkylammonium hydroxides are very strong bases and have the advantage of being soluble in water and in many organic solvents. However, these bases, except for some scattered reports, were not fully utilized in carboxylic ester hydrolysis, particularly for polypeptide esters. The use of tetraalkylammonixim hydroxides in hydrolysis of small easily soluble polypeptide esters does not show much of an advantage over the traditional conditions such as NaOH in aqueous acetone. However, fully-protected larger polypeptide chains, which show... 

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