Thioesters function

The 2-pyridyl and related 2-imidazolyl disulfides have found special use in the closure of large lactone rings.118 This type of structure is encountered in a number of antibiotics which, because of the presence of numerous other sensitive functional groups, require mild conditions for cyclization. It has been suggested that the pyridyl and imidazoyl thioesters function by a mechanism in which the heterocyclic nitrogen acts as... 

Thioacid- and thioester-modified peptides have been used in the silver-mediated condensations of peptide fragments. 65-70 Thioester-functionalized peptides have also been utilized as the starting precursors for the formation of cyclic peptides 71,72 as well as alkyl and aryl substituted amides. 73 ... 

Other very important applications of C-terminal thioester-functionalized peptides include their usage in the condensation of large unprotected peptide fragments (ligation see Vol. E22a, Section 4.1.5). 4,5,74 In this process the thioester-modified unprotected peptide reacts with the N-terminal cysteine of a second unprotected peptide giving a thioester intermediate. This step is followed by a rapid intramolecular S—>N shift with formation of the thermodynamically favored amide bond at the ligation site. 

In the synthesis of a-amino acids [290] through addition of the carbanion of MMTS to nitriles the overall process involves three other steps frequently encountered in sulfur-mediated chemistry a Pummerer-type rearrangement, with a less common migration of a methylthio group, and a Raney nickel desulfurization following transesterification of the thioester function. 

Thiol groups are introduced into antigens by reaction of their primary amino groups with SATA. This is the same kind of reaction as that used for incorporation of biotin molecules into antigens or of SMCC into AChE and requires the same precautions. The thioester function of SATA is then hydrolyzed in the presence of hydroxylamme in order to reveal the thiol groups. Excess reagents (SATA, hydroxylamme) are finally eliminated by molecular sieve chro-... 

Coenzyme A (CoA) is a cofactor that has been estimated to be used by about 4% of all enzymes, although more recent analysis of the BRENDA database (http //www.brenda.uni-koeln.de/) suggests the number may be closer to 9% (1). The biochemical pathways and processes involving CoA thioesters are diverse and widespread, whereas the kinds of reactions involved primarily follow the inherent reactivity of the thioester functionality. This article provides a brief overview of CoA biosynthesis and a summary of the common types of reactions of CoA thioesters. Also presented is a brief introduction to structural studies and a more extensive description of some types of analogs of natural CoA thioesters that have been employed as mechanistic probes for CoA using enzymes. The application of CoA derivatives and CoA biosynthetic enzymes for the tagging of carrier proteins and carrier protein fusions is also described. 

Certain CoA thioester using enzymes catalyze reactions at the fS-carbon or other carbons of the acyl group more distant from the thioester functionality. The fatty acid fi-oxidation cycle provides some examples (Fig. 3). Fatty acids 7 enter the cycle by initial conversion to the CoA ester 8, which is then oxidized to the a,P-unsaturated thioester 9 by a flavin-dependent enzyme. Addition of water to the double bond to form the fi-hydroxy thioester 10 is catalyzed by the enzyme crotonase, which is the centerpiece of the crotonase superfamily of enzymes that catalyze related reactions (37), which is followed by oxidation of the alcohol to form the fi-keto thioester 11. A retro-Claisen reaction catalyzed by thiolase forms acetyl-CoA 12 along with a new acyl-CoA 13 having a carbon chain two carbons shorter than in the initial or previous cycle. 

Thioester functions have again featured in some highly selective aldol condensations. The oxazoline (314), derived from (L)-aspartic acid, gives very largely isomers (315) upon enolisation, aldol... 

The proposed mechanism, which is based on the double carbonylation of styrene oxide, is shown in Scheme 6.2. The generation of an acylcobalt carbonyl complex from the reaction of cobalt tetracarbonyl anion with an alkyl halide is followed by reaction with a thiirane. This species can undergo carbonylation, the thioester function can undergo hydrolysis to reveal a sulfido nucleophile, and intramolecular cydization then produces thietan-2-one. The thietan-2-one can undergo ring cleavage and the mercapto acid results by protonahon. 

The polymerization of racemic Leu-SEt and Val-SEt in water yields short atactic peptides. However, it was found recently that when these racemic thioesters are polymerized in the presence of in-situ CDI-activated racemic Leu or Val, isotactic copeptides are formed primarily. In these reactions, the thioester functions both as an initiator and a multimer, as the growing sites of the -sheets can recognize equally well the NCA and the thioesters of the amino acids, as shown schematically for the Val polymerization in Figure 8.23. 

In addition to dialkylthiopropionate secondary antioxidants a similar situation was shown to apply in the case of higher MW compounds with thioester functionalities, e.g., Seenox 4125 with a MW of 1156, also hindered phenols, alkyl phosphites are polyhindered amines and Irganox 1050. 

Thioesters.—Mixed anhydrides prepared from 2,4,6-trichlorobenzyl chloride and a carboxylic acid react with various thiols in the presence of 4-dimethyl-aminopyridine to give thioesters in 78—86% isolated yield.Somewhat less impressive yields were obtained in a few of the cases studied when l-fluoro-2,4,6-trinitrobenzene was used to couple the acid and the thiol.Treatment of 1-acylimidazoles with thiols in the presence of a catalytic amount of Mg(OEt)2 furnishes thioesters in good yields. Diphenyl-2-oxo-3-oxazolinylphosphonate brings about effective reaction between acids and thiols. Thiolacetates are efficiently prepared using the reaction of an alcohol with triphenylphosphine and di-isopropyl azodicarboxylate in the presence of thiolacetic acid/ A synthesis of some amino-acid derivatives containing the thioester functional group is achieved by the reaction of a vinyloxyborane with a Schiffs base (Scheme 56). ... 

Lastly, the methodology gives exceUent yields and enantioselectivities when P,P-disubstitutedunsaturated thioesters are used as substrates (R =SEt, Scheme 73), regardless of whether an aromatic p-substituent is present (Fig. 19). The thioester functionality allows easy conversion to the corresponding unsaturated carboxylic ester or ketones through Ag-mediated and Pd-catalysed procedures, respectively [111]. 

Diene)Fe(GO)3 complexes have been used to construct 2-azaspiro[5.5]undecane and tricyclic ring systems. Intramolecular coupling reactions between diene-Fe(GO)3 complexes and a pendant olefinic group or pendant alcohols have been studied.The cyclization of allylic thioester-functionalized cyclohexadiene iron tricarbonyl... 

FUNCTIONAL GROUP proposed that the pyridyl and imidazoyl thioesters function by a mechanism in BY L LEOT which the heterocyclic nitrogen also acts as a base, deprotonating the alcohol group. 

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