Hydrolysis of thiol esters

The hydrolysis of thiol esters is achieved in either acidic or basic media. Alcoholic solutions of hydrogen chloride or potassium hydroxide are the most common reagents. Dithiols, hydroxy mercaptans/ and mercapto ethers, ketones, and acids have been prepared by this method. The corresponding thiol esters are obtained by the addition of thioacetic acid to oxides and olefinic acids or by the action of its potassium salt on halo ketones or sulfonic esters. ... 

Soft metal ions such as Hg and Ag have long been known to react readily with organo sulfur compounds, and a review of the metal ion-promoted reactions which can occur is available. The hydrolysis of thiol esters (equation 25), thione esters (equation 26) and thiolbenzimidate esters (equations 27 and 28) are all strongly promoted by Hg" in aqueous solution at pH <3... 

R C—SR 1 OR Alcoholysis or hydrolysis of thiol esters, thiolysis of esters. 

But we can assign to GSH more specific functions also. It participates in transpeptidations and oxidation reductions as well as in hydration-dehydration reactions. Perhaps this large variety of reactions has more in common than appears at first sight. Many of the transpeptidation reactions have been shown to occur with enzymes such as the cathepsins which require SH groups for activity. Hydrolysis of thiol esters by papain has been recently demonstrated (66) and the formation of thiol esters as intermediates in transpeptidations still remains to be explored. In the glyoxalase reaction the actual substrate may be the hydrated form of the aldehyde, in which case the reaction mechanism would be one of dehydration and hydrolysis rather than of a hydrogen shift. Thus the reaction will bear some similarity to the aconitase reaction which is stimulated by SH compounds and ferrous ions (67). 

TABLE 7.11. Rate Constants for Hydrolysis of Thiol Esters and Esters... 

Fig. 13 A semi-synthetic abzyme. Selective derivatization of lysine-52 in the heavy chain of MOPC315 creates a thiol, then bonded to an imidazole, which gives an abzyme capable of improved hydrolysis of coumarin ester [42] with ca, = 0.052 min-1.

Only very few among the common amino acids possess a pK within the range 5.8-7.0. Therefore, the imidazole ring of histidine was suspected very early to represent the group responsible for nucleophilic attack on the substrate (38). The pK of free imidazol is 6.9 (39) that of imidazol, contained in histidine or its peptides, varies between 5.6 and 7.1 (40). Imidazol is well known to form unstable acyl derivatives, which undergo spontaneous hydrolysis because of the presence of the resonating triad unit —-N—C= N— (41). In addition, imidazol and its derivatives catalyze the hydrolysis of certain esters, especially those derived from phenols (42). Likewise, the behavior of imidazol towards thio esters reflects exactly the specificity of ChE s (see IV, 4). Thus, thiol esters are split (43), whereas thiono esters are resistant (21). 

The utility of thiol esters and carbonates as protecting groups is limited by their vulnerability to hydrolysis, The poor overlap between the non-bonded electrons on the sulfur atom (3p) and the n-system of the carbonyl (2p) precludes or diminishes resonance stabilisation of the type enjoyed by normal esters thereby raising their ground state energy, The carbonyl group of the thioester is more electrophilic than a normal ester and hence more reactive. Thiocarbonate derivatives are marginally more stable. The 5-benzoyl derivative of cysteine is 95% hydrolysed in 30 minutes with 2 M ammonia whereas the 5-benzyloxycarbonyl derivative is only 20% hydrolysed in 30 minutes under the same conditions.54... 

As described in a previous section, the imidazole group of a histidyl residue is involved in a most direct fashion in the catalytic action of hydrolytic enzymes (see Table 2—1). This fact attracted mudi attention among phyrical organic chemists, and imidazole and imidazole compounds became the first organic bases to have been established as catalysts for ester hydrolysis. Since the weakly basic imidazolyl group is not capable of directly displacing the much mtxe basic alkoxide ions from normal esters, most studies have dealt with the catalysis of the hydrolysis of activated esters, such as phenyl acetates and thiol esters ... 

Thiols are more acidic than the corresponding alcohols and are converted into their salts using alkali metal hydroxides or alkoxides. The thiolate salts are powerful nucleophiles, a property which has been used in the cleavage of methyl esters and methyl ethers. The combination of a hard acid and a soft base such as lithium propanethiolate (Li SPr) may favour attack on the methyl group of an ester and lead to alkyl-oxygen fission of the ester, rather than the more common addition of a nucleophile to the carbonyl group and consequently acyl-oxygen fission. This is particularly useful in the hydrolysis of hindered esters. 

Jencks WP, Gilchrist M. Free energies of hydrolysis of some esters and thiol esters of acetic acid. J. Am. Chem. Soc. 1964 86 4651-4654. 

The substitution reactions discussed in this review will be restricted primarily to the thiolate anion, RS acting as a nucleophile. This may be present initially when a metal thiolate, such as silver(i) or lead(ii), is employed, or may be generated in solution in the presence of a base such as sodium hydroxide or trimethylamine. The acidity of the thiol is important if the RS anion acts as a nucleophile in a neutral thiol solution. Thiolate nucleophiles can be obtained in non-aqueous solution by treatment of thiol esters, such as CH3COSR, with strong non-nucleophilic basest or by hydrolysis of thiourea derivatives ... 

A discussion Is given of standard states appropriate to biochemical thermodynamics. Tabulated are Gibbs energies of hydrolysis of esters of acetic acid and related compounds, of thiol esters, amides, phosphates, and of glycolysis (and of decarboxylation). 

Sodium ethyl thiosulfate [26264-37-9] is also known as Bunte s salt after the name of its discoverer. Bunte salts may be thought of as esters of thiosulfuric acid (94—96). In essentially all of their chemical reactions, the cleavage is between the divalent and hexavalent sulfur atom. For example, acid hydrolysis produces a thiol and the acid sulfate ... 

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