Carboxylic esters, acylation hydrolysis

Other carbanionic groups, such as acetylide ions, and ions derived from a-methylpyridines have also been used as nucleophiles. A particularly useful nucleophile is the methylsulfinyl carbanion (CH3SOCHJ), the conjugate base of DMSO, since the P-keto sulfoxide produced can easily be reduced to a methyl ketone (p. 549). The methylsulfonyl carbanion (CH3SO2CH2 ), the conjugate base of dimethyl sulfone, behaves similarly, and the product can be similarly reduced. Certain carboxylic esters, acyl halides, and DMF acylate 1,3-dithianes (see 10-10. )2008 Qxj(jatjye hydrolysis with NBS or NCS, a-keto aldehydes or a-... 

Carboxylic acid derivative (Section 20 1) Compound that yields a carboxylic acid on hydrolysis Carboxylic acid de nvatives include acyl chlondes acid anhydndes esters and amides... 

The reverse reactivity is noted in the acid-catalyzed hydrolysis of the esters. Pyrrole-3-carboxylic esters are hydrolyzed upon dissolution in concentrated sulfuric acid and subsequent dilution with ice. Evidence has been presented indicating that unimolecular acyl—O fission forms the resonance-stabilized pyrrolyl acylium ion (B-77MI30505). 

As free DHAs are highly unstable compounds that readily undergo hydrolysis, they have generally been synthesized as their A-acyl derivatives or carboxylic esters and amides. For this reason DHAs occur in nature primarily as A-acyl derivatives or as part of a peptide sequence. Free DHAs 2 (Scheme 1) have not been characterized most probably they exist as imines 1 and consequently they readily undergo hydrolysis to give the corresponding a-oxo acid 3 and ammonia. 

Because the acidic hydrogen is the usual cause of undesired reactivity, carboxylic acids are commonly protected as esters. Most often, simple methyl esters are used. The ester can be prepared via the acyl chloride or by Fischer esterification (see Section 19.4). The ester group can be converted back to the carboxylic acid by hydrolysis under acidic or basic (saponification) conditions (see Section 19.5). 

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 ... 

The in situ racemization can be achieved by different means either spontaneously or catalytically. Due to their chemical properties certain substrates may racemize spontaneously under the reaction conditions. Useful catalysts could be ordinary chemicals such as bases, transition metal complexes and in theory another type of biocatalyst. Having identified a suitable enzyme promoting the enantiomer-differentiating process by hydrolysis or alcoholysis of a carboxylic ester or by acylation of an alcohol one has to find the appropriate racemizing catalyst. Lipase and catalyst must tolerate each other they must work under identical conditions. The product must be chemically and configurationally stable in the presence of the catalyst. 

The bile-salt-dependent lipase of pancreatic juice has many names such as cholesterol esterase, nonspecific lipase, the most rational being carboxyl ester lipase [27], In the case of water-insoluble substrates this enzyme has an absolute requirement for bile salts specifically having hydroxyl groups in the 3a and la positions [28.29]. The best documented role for this enzyme is to allow the absorption of dietary cholesterol, through hydrolysis of cholesterol esters in the lumen. The enzyme also catalyzes the esterification of cholesterol and a role for it has been proposed in cholesterol absorption [30]. In addition, a wide range of primary and secondary fatty acyl esters including glycerides, vitamin A and E esters are hydrolyzed by this enzyme. 

The latter step in the mechanism—the regeneration of the active enzyme—is important in the development of AChEls. If the enzyme becomes acylated by a functional group (i.e., carbamyl or phosphate) that is more stable to hydrolysis than a carboxylate ester, the enzyme remains inactive for a longer period of time. Application of this chemical principle regarding rates of hydrolysis led to discovery and design of two classes of AChEls, the reversible inhibitors and the irreversible inhibitors. 

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... 

All carboxylic esters syntheses in cells depend on activated acyl species. The most important are thioesters formed between coenzyme A (Fig. 1) and the acyl group. There are different ways for the formation of the thioester (acyl-CoA), depending on the metabolic pathway, as summarized in Figure 2. The presence of the sulfur atom diminishes the possibility of resonance, usually stabilizing esters, and the energy liberated by the hydrolysis of acyl-CoA is around 31 kJ/mol. 

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

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