Thiols thioester formation

Thioamide formation benzodiazepinone, 505 heteiodiazepinone, 621 phosphorus pentasulf ide, 323, 600 Thioazole formation, nitrile addition, 301 Thiocarbamate formation, 588 phenol, 95 rearrangement, 517 Thioenol ether formation, 185, 517 addition-elimination, 554 Thioester formation, mixed anhydride, 184 Thioether formation, 241, 300, 413, 416 alkylation, 586, 588 aromatic displacement, 416 Thiohydantoin formation, 293 Thiol interchange, benzothiazole formation, 422... 

Scheme 36. The [NiS] mediated thioester formation from alkyl, CO, and thiols. [The alkyl and acyl complexes 38 and 39 were characterized by X-ray structure analysis for L = py (38) and L = PMe3 (39).]...

Scheme 36 represents the first example for a [NiS] mediated formation of thioesters from alkyl, CO, and thiol groups in a cyclic way. All intermediates shown in Scheme 37 could be intercepted and characterized by spectroscopic methods and X-ray structure analysis. They permit a detailed insight into the individual steps of thioester formation that may take place in an analogous way at the active site of CODH when acetyl-CoA is synthesized. 

DEPC in combination with NEtj has proved to be a new efficient reagent for the direct C-formylation of active methylene compounds with carboxylic acids and also for the iV-acylation (peptide bond formation), 5-acylation (thioester formation) and O-acylation (esterification).4,5 Reaction of DEPC with carboxylic acids 11 in the presence of triethylamine produces transient acyl cyanides, which in the presence of alcohols or thiols results in the formation of the corresponding esters (12) or thioesters (13). 

A thiol auxiliary, Dmmb mediated thioester formation, above, and a cysteine residue might also play a role in the formation of a thioester. It was suggested that a thioester is formed during the treatment of a protected cysteine-containing peptide with anhydrous hydrogen fluoride [57]. In order to confirm the formation of... 

In the previous sections, thioester formation at the tert-amide moiety was discussed, and the thioester intermediate was predominant in the equilibrium mixture tmder acidic conditions. The intermediate was sufficiently stable, even under neutral conditions, to allow it to react with the external thiol by intermolecular transthioes-terification. On the other hand, a thioester intermediate at the cysteine residue is easily transformed into the amide, even under aqueous acidic conditions such as a 0.1% aqueous TFA solution. Special sequences containing a cysteine residue were, however, reported. Peptide 42 containing a Gly-Cys, His-Cys, or Cys-Cys sequence can be transformed into the corresponding glycine, histidine, or cysteine thioester 44 in the presence of thiols under acidic conditions (Scheme 14) [75, 76]. The C-terminal cysteine carboxylic acid is more easily converted into the thioester than... 

Authors stated that 2.5 mol% of azobisisobutyronitrile (AIBN) was used as an initiator to obtain complete conversion of the monomer after 2 h, at 80 °C. Low temperatures are favourable for thiol-ene additions. However, for polymerisations, the reaction temperature should be increased to avoid crystallisation of the polymer during polymerisation [33]. Gel permeation chromatography (GPC) analyses showed that fatty acid-based polyesters with Mn = 12 kDa (reactions 2 and 3, Scheme 6.11) could be synthesised via thiol-ene polymerisation. However, this approach was less suitable for the polymerisation of reactions 1 and 3, Scheme 6.11, which led to a Mn value of only 5 kDa. The high reactivity of the anhydride functionalities towards nucleophiles (in this case the thiol groups) caused the scission of the monomer or polymer backbone via thioester formation, leading to a decrease in molecular weight [33]. 

Thus the biological importance of the phosphopantetheine group as a catalytic centre is widespread. Numerous examples of the role of coenzyme A are known and the list of phosphopantetheine enzyme centres is growing. The principal reactive element is the thiol, although other attributes of the unique peptide will undoubtedly prove important. The thiol serves as the site of thioester formation and its particular chemical attributes facihtate acyl transfer, carbon chain modification and condensation reactions. The phosphopantetheine thiol represents the most... 

Nitrophthalic thioesters, formation for identification of thiols 276 Nitropolyhalobenzenes, reaction with copper(i) thiolates 742 Nitroso compounds, for oxidation of thiols 800... 

The really unique reaction of the lipoate centre in ct-keto acid metabolism is the oxidative thioester formation from a thiamine-coordinated active aldehyde . Thiol transacetylase and dithiol-disulphide oxidation reduction roles are well-known attributes of other biological thiols. Unfortunately mechanistic studies on this reductive acylation of a cyclic disulphide have so far received little attention. Proposals that a lipoic acid-thiamine pyrophosphate compound was the functional entity in a-keto acid oxidation have been completely abandoned, but data supporting this concept remain unexplained. Investigations in this area might have some relevance for the reductive acylation process. 

Ester and Thioester Formation. These reactions occur through the same O-acylurea or anhydride active intermediate as in the amide coupling reactions, and the discussion of associated problems applies here as well. In general, alkyl and (particularly) aryl thiols can be efficiently coupled to carboxylic acids using DCC. Reactions of primary and secondary alcohols proceed reliably, but require the presence of an acylation catalyst. This is usually 4-Dimethylaminopyridine (DMAP), " (see also 1,3-Dicyclohexylcarbodiimide—4-Dimethylaminopyridine), but others have been used including 4-pyrrolidinopyridine and pyridine (.solvent) with catalytic p-Toluenesulfonic Acid The acylation of more hindered alcohols often re.sults in reduced yields however, even f-butanol can be acylated, providing a useful route to t-butyl esters. Various other carbodiimide derivatives have also been used in the preparation of esters. As with amides, which are not limited to intermolecular reactions, a wide variety of lactones can also be synthesized. ... 

The final step in the /3-oxidation cycle is the cleavage of the /3-ketoacyI-CoA. This reaction, catalyzed by thiolase (also known as j8-ketothiolase), involves the attack of a cysteine thiolate from the enzyme on the /3-carbonyI carbon, followed by cleavage to give the etiolate of acetyl-CoA and an enzyme-thioester intermediate (Figure 24.17). Subsequent attack by the thiol group of a second CoA and departure of the cysteine thiolate yields a new (shorter) acyl-CoA. If the reaction in Figure 24.17 is read in reverse, it is easy to see that it is a Claisen condensation—an attack of the etiolate anion of acetyl-CoA on a thioester. Despite the formation of a second thioester, this reaction has a very favorable A).q, and it drives the three previous reactions of /3-oxidation. 

The thioester hypothesis can be summed up as follows the formation of thiols was possible, for example, in volcanic environments (either above ground or submarine). Carboxylic acids and their derivatives were either formed in abiotic syntheses or arrived on Earth from outer space. The carboxylic acids reacted under favourable conditions with thiols (i.e., Fe redox processes due to the sun s influence, at optimal temperatures and pH values) to give energy-rich thioesters, from which polymers were formed these in turn (in part) formed membranes. Some of the thioesters then reacted with inorganic phosphate (Pi) to give diphosphate (PPi). Transphosphorylations led to various phosphate esters. AMP and other nucleoside monophosphates reacted with diphosphate to give the nucleoside triphosphates, and thus the RNA world (de Duve, 1998). In contrast to Gilbert s RNA world, the de Duve model represents an RNA world which was either supported by the thioester world, or even only made possible by it. 

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