Active esters hydrolysis

Buckingham, D. A., and C. R. Clark, Metal-hydroxyde-promoted hydrolysis of activated esters. Hydrolysis of 2,4-dinitrophenyl acetate and 4-nitrophenyl acetate , Aust. J. Chem., 35,431-436 (1982). 

The structure-reactivity relationship for polyamine derivatives in activated ester hydrolysis was previously established [46]. Polyvinylamine (PVA), linear (LPEI) and branched (41% branching) polyethylene imine (BPEI) as well as their dodecyl- and imidazole-substituted derivatives with an approximate and equal degree of substitution (16-20%) were applied as catalysts. The compoundsp-NPA and 4-acetoxy-3-ni-trobenzoic acid (ANBA) as well as some of their homologues were used as substrates. At an excessive catalyst concentration relative to the substrate concentration, reactions proceeded at pseudo first order. In each series of polymers, the reaction rate constant was increased considerably by substitution of dodecyl (hydrophobic site) by imidazolyl (catalytic center) and when a charged substrate (electrostatic effect) was employed. At an equal degree of substitution, the catalytic activity increased in the following order LPEK PVA < BPEI. 

Brown RA (1962) The linear enthalpy-entropy effect. J Org Chem 27 3015-3026 Buckingham DA, Clark C (1982) Metal-hydroxide promoted hydrolysis of activated esters. Hydrolysis of 2,4-dinitrophenylacetate and 4-nitrophenylacetate. Aus J Chem 35 431-436... 

Ketopregnan-21-oic Acids, the 17(3-Carboxy Androstanes, and the D-Homocorticoids. In the course of studies on the metabohsm of fluocoitolone (103) the formation of the water-soluble carboxyhc acid (105, R = H) was reported. As a free 21-hydroxyl is not necessary for antiinflammatory activity, it was concluded that the esters (105, R = alkyl) of the preceding metabohte would possess antiinflammatory activity on topical administration but would be devoid of systemic activity when hydrolysis to the free acid occurs followed by... 

Acidic Cation-Exchange Resins. Brmnsted acid catalytic activity is responsible for the successful use of acidic cation-exchange resins, which are also soHd acids. Cation-exchange catalysts are used in esterification, acetal synthesis, ester alcoholysis, acetal alcoholysis, alcohol dehydration, ester hydrolysis, and sucrose inversion. The soHd acid type permits simplified procedures when high boiling and viscous compounds are involved because the catalyst can be separated from the products by simple filtration. Unsaturated acids and alcohols that can polymerise in the presence of proton acids can thus be esterified directiy and without polymerisation. 

The threat of accidental misuse of quaternary ammonium compounds coupled with potential harmful effects to sensitive species of fish and invertebrates has prompted some concern. Industry has responded with an effort to replace the questionable compounds with those of a more environmentally friendly nature. Newer classes of quaternaries, eg, esters (206) and betaine esters (207), have been developed. These materials are more readily biodegraded. The mechanisms of antimicrobial activity and hydrolysis of these compounds have been studied (207). AppHcations as surface disinfectants, antimicrobials, and in vitro microbiocidals have also been reported. Examples of ester-type quaternaries are shown in Figure 1. 

In contrast to the hydrolysis of prochiral esters performed in aqueous solutions, the enzymatic acylation of prochiral diols is usually carried out in an inert organic solvent such as hexane, ether, toluene, or ethyl acetate. In order to increase the reaction rate and the degree of conversion, activated esters such as vinyl carboxylates are often used as acylating agents. The vinyl alcohol formed as a result of transesterification tautomerizes to acetaldehyde, making the reaction practically irreversible. The presence of a bulky substituent in the 2-position helps the enzyme to discriminate between enantiotopic faces as a result the enzymatic acylation of prochiral 2-benzoxy-l,3-propanediol (34) proceeds with excellent selectivity (ee > 96%) (49). In the case of the 2-methyl substituted diol (33) the selectivity is only moderate (50). 

Optically Active Acids and Esters. Enantioselective hydrolysis of esters of simple alcohols is a common method for the production of pure enantiomers of esters or the corresponding acids. Several representative examples are summarized ia Table 4. Lipases, esterases, and proteases accept a wide variety of esters and convert them to the corresponding acids, often ia a highly enantioselective manner. For example, the hydrolysis of (R)-methyl hydratropate [34083-55-1] (40) catalyzed by Hpase P from Amano results ia the corresponding acid ia 50% yield and 95% ee (56). Various substituents on the a-carbon (41—44) are readily tolerated by both Upases and proteases without reduction ia selectivity (57—60). The enantioselectivity of many Upases is not significantly affected by changes ia the alcohol component. As a result, activated esters may be used as a means of enhancing the reaction rate. 

Hydrolysis of esters and amides by enzymes that form acyl enzyme intermediates is similar in mechanism but different in rate-limiting steps. Whereas formation of the acyl enzyme intermediate is a rate-limiting step for amide hydrolysis, it is the deacylation step that determines the rate of ester hydrolysis. This difference allows elimination of the undesirable amidase activity that is responsible for secondary hydrolysis without affecting the rate of synthesis. Addition of an appropriate cosolvent such as acetonitrile, DMF, or dioxane can selectively eliminate undesirable amidase activity (128). 

A polymer-supported sulfonamide, prepared from an amino acid activated ester and a polystyrene-sulfonamide, is stable to acidic hydrolysis (CF3COOH HBr/ HOAc). It is cleaved by the safety-catch method shown below. ... 

The Zincke reaction has also been adapted for the solid phase. Dupas et al. prepared NADH-model precursors 58, immobilized on silica, by reaction of bound amino functions 57 with Zincke salt 8 (Scheme 8.4.19) for subsequent reduction to the 1,4-dihydropyridines with sodium dithionite. Earlier, Ise and co-workers utilized the Zincke reaction to prepare catalytic polyelectrolytes, starting from poly(4-vinylpyridine). Formation of Zincke salts at pyridine positions within the polymer was achieved by reaction with 2,4-dinitrochlorobenzene, and these sites were then functionalized with various amines. The resulting polymers showed catalytic activity in ester hydrolysis. ... 

Poly(L-malate) decomposes spontaneously to L-ma-late by ester hydrolysis [2,4,5]. Hydrolytic degradation of the polymer sodium salt at pH 7.0 and 37°C results in a random cleavage of the polymer, the molecular mass decreasing by 50% after a period of 10 h [2]. The rate of hydrolysis is accelerated in acidic and alkaline solutions. This was first noted by changes in the activity of the polymer to inhibit DNA polymerase a of P. polycephalum [4]. The explanation of this phenomenon was that the degradation was slowest between pH 5-9 (Fig. 2) as would be expected if it were acid/base-catalyzed. In choosing a buffer, one should be aware of specific buffer catalysis. We found that the polymer was more stable in phosphate buffer than in Tris/HCl-buffer. 

Acid-catalyzed ester hydrolysis can occur by more than one mechanism, depending on the structure of the ester. The usual pathway, however, is just the reverse of a Fischer esterification reaction (Section 21.3). The ester is first activated toward nucleophilic attack by protonation of the carboxyl oxygen atom, and nucleophilic addition of water then occurs. Transfer of a proton and elimination of alcohol yields the carboxylic acid (Figure 21.8). Because this hydrolysis reaction is the reverse of a Fischer esterification reaction, Figure 21.8 is the reverse of Figure 21.4. 

Active Figure 21.8 MECHANISM Mechanism of acid-catalyzed ester hydrolysis. The forward reaction is a hydrolysis the back-reaction is a Fischer esterification and is thus the reverse of Figure 21.4. Sign in afwww.thomsonedu.com to see a simulation based on this figure and to take a short quiz. 

Aliphatic hydrocarbons such as hexane also have been reported to react with PCI3 and AICI3. Surface-active esters of phosphinic acids are obtained in good yields by treatment of the intermediate addition compound with an alcohol or phenol followed by hydrolysis [172] see Eqs. (103) to (105) ... 

Stereoinversion Stereoinversion can be achieved either using a chemoenzymatic approach or a purely biocatalytic method. As an example of the former case, deracemization of secondary alcohols via enzymatic hydrolysis of their acetates may be mentioned. Thus, after the first step, kinetic resolution of a racemate, the enantiomeric alcohol resulting from hydrolysis of the fast reacting enantiomer of the substrate is chemically transformed into an activated ester, for example, by mesylation. The mixture of both esters is then subjected to basic hydrolysis. Each hydrolysis proceeds with different stereochemistry - the acetate is hydrolyzed with retention of configuration due to the attack of the hydroxy anion on the carbonyl carbon, and the mesylate - with inversion as a result of the attack of the hydroxy anion on the stereogenic carbon atom. As a result, a single enantiomer of the secondary alcohol is obtained (Scheme 5.12) [8, 50a]. 

Proteases, which originally catalyze the amidic carbon-nitrogen bond breaking, also catalyze ester hydrolysis. However, in this case, the catalytic mechanism is hkely very similar and consists in the preliminary attack of the active site serine on the carbonyl carbon atom [103]. 

Lipases are the enzymes for which a number of examples of a promiscuous activity have been reported. Thus, in addition to their original activity comprising hydrolysis of lipids and, generally, catalysis of the hydrolysis or formation of carboxylic esters [107], lipases have been found to catalyze not only the carbon-nitrogen bond hydrolysis/formation (in this case, acting as proteases) but also the carbon-carbon bond-forming reactions. The first example of a lipase-catalyzed Michael addition to 2-(trifluoromethyl)propenoic acid was described as early as in 1986 [108]. Michael addition of secondary amines to acrylonitrile is up to 100-fold faster in the presence of various preparations of the hpase from Candida antariica (CAL-B) than in the absence of a biocatalyst (Scheme 5.20) [109]. 

The Structure of the Active Surface of Cholinesterases and the Mechanism of Their Catalytic Action in Ester Hydrolysis... 

Fungal cutinase catalyzes hydrolysis of model substrates and in particular p-nitrophenyl esters of short chain fatty acids, providing a convenient spectro-photometric assay for this enzyme activity [101,102,116]. Hydrolysis of model esters by this cutinase showed the high degree of preference of this enzyme for primary alcohol ester hydrolysis. Wax esters and methyl esters of fatty acids were hydrolyzed at low rates. Alkane-2-ol esters were hydrolyzed much more slowly than wax esters and esters of mid-chain secondary alcohols were not... 

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