Thiol transesterification

Another advantage to the use of a thiol additive is that the abundance of free thiol groups in the reaction environment will prevent the oxidation of the cysteine thiol at the N-terminal of the other peptide. Without added thiol transesterification catalysts, disulfide formation resulting in dimerization of the Cys-peptide would be a dominant side reaction in aqueous, oxygenated buffer conditions. 

Several additional points should be made. First, although oxygen esters usually have lower group-transfer potentials than thiol esters, the O—acyl bonds in acylcarnitines have high group-transfer potentials, and the transesterification reactions mediated by the acyl transferases have equilibrium constants close to 1. Second, note that eukaryotic cells maintain separate pools of CoA in the mitochondria and in the cytosol. The cytosolic pool is utilized principally in fatty acid biosynthesis (Chapter 25), and the mitochondrial pool is important in the oxidation of fatty acids and pyruvate, as well as some amino acids. 

There are very few known methods, for transesterifications using bulky alcohols. Thiol esters undergo ready mercury(II) trifluoroacetate-catalyzed transesterifications with tert-butyl alcohol. Potassium tert-butoxide in the... 

Alcohols can also be prepared from support-bound carbon nucleophiles and carbonyl compounds (Table 7.4). Few examples have been reported of the a-alkylation of resin-bound esters with aldehydes or ketones. This reaction is complicated by the thermal instability of some ester enolates, which can undergo elimination of alkoxide to yield ketenes. Traces of water or alcohols can, furthermore, lead to saponification or transesterification and release of the substrate into solution. Less prone to base-induced cleavage are support-bound imides (Entry 2, Table 7.4 see also Entry 3, Table 13.8 [42]). Alternatively, support-bound thiol esters can be converted into stable silyl ketene acetals, which react with aldehydes under Lewis-acid catalysis (Entries 3 and 4, Table 7.4). 

C-Carboxylation of enolates.1 Carboxylation of potassium enolates generated from silyl enol ethers is not regioselective because of extensive enolate equilibration. Regiospecific C-carboxylation of lithium enolates is possible with carbonyl sulfide in place of carbon dioxide. The product is isolated as the thiol methyl ester. If simple esters are desired, transesterification can be effected with Hg(OAc)2 (8, 444). Carboxylation of ketones in this way in the presence of NaH and DMSO is not satisfactory because of competing alkylation of the enolate.2 Example ... 

In addition to thioesterifications employing the C-terminal condensation with alkyl-thiols, the Danishefsky group demonstrated an alternative type of thioesterification (Scheme 11.6) [74], A suitably side chain-protected peptide acid is condensed with an amino acid 2-dithioethyl phenyl ester. The 2-dithioethyl phenyl ester is prone to rearrangement to a thioester through O S transesterification under reducing (NCL) conditions. 

The chemistry of Iipoic acid is described in the chapter (pp. 1394-5). A thiol ester of exactly the kind described in the problem is indeed involved and it is deacylated, though by CoASH rather than an alcohol, and the dithiol is indeed recycled as the disulfide. The oxidation to the cyclic disulfide is carried out in Nature by FAD. In the chapter we suggest that the oxidation of the dithiol to the disulfide is a separate step from the transesterification. You may well think that the evidence in this problem suggests that the oxidation may take place first. 

In the remaining steps, acetic and malonic acids react, not as CoA esters, but as thiol esters of acyl carrier protein (ACP), a small protein with a prosthetic group quite similar to CoA. These esters are formed by (2) and (3). which we recognize as examples of transesterification. 

Acylation of a simple thiol with an alkyl carboxylate is not a very suitable method for preparation of S-alkyl thiocarboxylates. Transesterification is, however, possible if either the thiol or the carboxylic ester is activated. The enhanced reactivity of boron, aluminum and silicon thiolates has been utilized for the synthesis of a large variety of thiocarboxylic S-esters, including hydroxy derivatives (from lactones). a,P-Unsaturated thiol esters, e.g. cinnamoyl or 2-butenoyl derivatives, are also accessible. Michael addition, an undesirable side reaction of thiols, is completely avoided if alkyl trimethylsilyl sulfides ortris(arylthio)boranes are applied. ... 

Before fatty acid synthesis can occur, however, the acyl groups of acetyl-CoA and malonyl-CoA are transferred to other thiols by means of a transesterification reaction. 

Syntheses of tellurol esters 3 are limited in comparison to thiol and selenol esters. A conventional preparative method is the reaction of tellurolate anions with acid chlorides or acid anhydride [113]. Co2(CO)8-mediated carbonylation of dichalcogenides (described in Sect. 3.1.10) is applicable to diphenyl ditel-luride, but the yields of tellurol esters are poor. They can also be obtained by transesterification of esters with z-Bu2AlTeBu. Reactions of tellurol esters 3 have not been extensively explored yet. However, generation of acyllithiums by Li-Te exchange is characteristic. They can be employed as acyl radical precursors in tin free radical reactions. 

Ready replacement of the bromine atoms in MeBiBr2 and PhBiBr2 occurred on treatment with sodium ethoxide, and the resulting diethoxides served as starting materials for a series of transesterification reactions with thiols, 1,2-diols, 1,2-dithiols, etc. ... 

A number of reversible reactions leading to covalent connections between reactants such as olefin metathesis, imine and hydrazone formation, transesterification, thiol-disulphide interchange, transacetalation and so on have been employed in DCC. 

The S5mthesis runs via transesterification, amidation and thiol-ene reactions to get aliphatic diols containing ester, these diols are then reacted with a biobased methyl diester. Most of these polyesters display a good thermal stability with temperature at 5% weight loss in the range 330-350°C. 

Another recent study on polyester synthesis through thiol-ene reactions for preparation of monomers from fatty-acid derivatives was described by Pang and co-workers [16]. Authors adopted the same approach for preparing aliphatic diols and diester from 10-undecen-l-ol, methyl 10-undecenoate and thiols. In parallel, they prepared aromatic diesters from methyl vanillate and a series of thermoplastic polyesters were synthesised by polycondensation of the diols and diesters using conventional transesterification methods. These materials were obtained with Mn values of 12-27 kDa and T values of -13 to 13 °C. 

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