Acyl transfer agents

Table 10 includes the results for skin irritation. No clear results have been obtained. All models are in agreement only for the absence of irritative potential of BDE 100. Multiple results from ToxTree are due to the five different alerts used by the model (Schiff base formation, SNAr, Acyl transfer agent, skin sensitization, and Michael acceptor). A global evaluation of ToxTree data could suggest that all the analyzed compounds are not able to induce skin sensitization. These predictions are in clear contrast with that obtained by applying CAESAR and in partial agreement with the results of Toxsuite. 

Diphenylthieno[3,4-d][l,3]dioxol-2-one 5,5-dioxide (304) can serve as an activating agent for peptide synthesis (76AG(E)444). The esters (305) are formed readily on admixture of a carboxylic acid with (304) in an aprotic solvent in the presence of pyridine. The activated esters (305) are stable, crystallizable compounds which react with amines readily to furnish the corresponding amides (Scheme 65). Competition experiments reveal that the esters (305) are more effective acyl transfer agents than the p- and o-nitrophenyl esters often used in peptide synthesis. 

To achieve better results a series of lipases was screened using the Chirazyme screening kit and analysis by gas chromatography with a chiral stationary phase. Candida antartica Lipase B, available as Novozyme 435, was chosen for further development with the acyl transfer agent vinyl propionate. 

In these instances, acylated amine cm thiol groups are resistant against the hydrolytic deaviige. Therefore, the polymers acted as acyl transfer agents but not as true catalysts. 

Prochiral Compounds. The enantiodifferentiation of prochi-ral compounds by lipase-catalyzed hydrolysis and transesterification reactions is fairly common, with prochiral 1,3-diols most frequently employed as substrates. Recent reports of asymmetric hydrolysis include diesters of 2-substituted 1,3-propanediols and 2-0-protected glycerol derivatives. The asymmetric transesterification of prochiral diols such as 2-0-benzylglycerol and various other 2-substituted 1,3-propanediol derivatives is also fairly common, most frequently with Vinyl Acetate as an irreversible acyl transfer agent. 

The asymmetric transesterification of cyclic me o-diols, usually with vinyl acetate as an irreversible acyl transfer agent, includes monocyclic cycloalkene diol derivatives, bicyclic diols, such as the ej o-acetonide in eq 12, bicyclic diols of the norbomyl type, andorganometallic l,2-bis(hydroxymethyl)ferrocenepossessing planar chirality. 

An acyl transfer agent which can be used for the synthesis of acid anhydrides is obtained from the reaction of an acid chloride with 4-benzylpyridine (equation 24). In this way benzoic acid anhydride and cinnamic acid anhydride were obtained in 72% and 57% yields, respectively. As the intermediate, 1-acyl-4-benzylidene-l,4-dihydropyridines, can be isolated, Ais procedure should be well suited for the preparation of mixed anhydrides. Mixed aromatic and aliphatic anhydrides can be prepared with 2-ben-zoylthio-l-methylpyridinium chloride and salts of carboxylic acids. These reactions are carried out in aqueous solution. Iliey make use of the high reactivity of esters of thiocarboxylic esters towards nucleophiles. The mixed anhydrides of benzoic acid with 3-phenylpropanoic acid, phenoxyacetic acid, isobu-tyric acid, p-toluic acid and cinnamic acid were formed in 82, 79,61,91 and 66% yields, respectively. 

As well as thiol esters, selenol esters (1) frequently exhibit a high and selective reactivity toward nucleophiles, which is enhanced even further by activation with heavy ions or oxidizing agents. These properties make selenol esters valuable acyl transfer agents. This review deals with general methods for the synthesis of selenol esters and their reactivity as acyl transfer agents. Furthermore, selenoesters (2), isomeric compounds of selenol esters, and their derivatives selenoamides (3) are also described. These compounds show the characteristic reactivity based on the carbon-selenium double bond. 

Selenol esters are expected to be a more reactive species than the corresponding thiol esters or 0x0 esters due to the comparatively weak bonding between carbon and selenium. The ability of the selenol esters to serve as active acyl transfer agents has been readily demonstrated by the easy conversion of the selenol ester (34 equation 15) to its corresponding acid (35), ester (36) or amide (37). This acyl-selenium bond cleavage has also been promoted by Cu and Cu" salts. - The isopropylidene derivative (38 equation 16) of ribofuranosylacetate has been converted to a lactone (40) in good yield via the selenol ester (39). 

Similar to enol esters, oximes can also be used as irreversible acyl transfer agents for lipase catalysis. Thus, instead of a di-enol ester, Athavale et al. [67] polymerized diols with bis(2,3-butane dione monoxime) alkanedioate using Lipozyme IM-20. The results obtained by activation with enol-esters and their corresponding oximes were comparable. No attempts were made to analyze the end-group of the polyester. 

Ketones. These imidazolium salts (1) are acyl transfer agents that react readily with organometallic compounds to give ketones. 

Acyl phosphates are too reactive to be acyl-transfer agents themselves, but are used for example to make acetyl coenzyme A, the intermediate used for acetyl transfer. 

Scheme 22 Selenol ester as acyl-transfer agent...

DMAP acts as an efficient acyl transfer agent, so that alcohols resistant to acetylation hy Acetic Anhydride-Pyridine usually react well in the presence of DMAP. Sterically hindered phenols can be converted into salicylaldehydes via a benzofurandione prepared by DMAP catalysis (eq 2). ... 

A further example of the value of thioesters as acyl transfer agents is the production of esters from these reagents by reaction with an alcohol and N-bromosuccinimide. ° Both thio- and seleno-esters are readily available from free acids via the intermediacy of the acid imidazolide or 1,2,4-triazolide, which react smoothly with thiols or selenols to give the desired esters in high overall yields. Thioesters can also be prepared directly from free acids and thiols by condensation in the presence of either diphenyl phosphorazidate or diethyl phos-phorocyanidate. S-Ethylthioesters can be obtained, generally in high yields, by... 

Many reactions like this occur in living organisms, and biochemists call them acyl transfer reactions. Acetyl-coenzyme A, discussed in Special Topic E in WileyPLUS, often serves as a biochemical acyl transfer agent. Acyl substitution reactions are of tremendous importance in industry as well, as described in the chapter opening essay and Special Topic C in WileyPLUS. 

C23H38N7O17P3S 809.577 The most important metabolic acyl transfer agent. In aerobic organisms the Ac group is formed by degradn. of carbohydrates, aminoacids and fats in anaerobic organisms by carbonylation of Me groups attached to tetrahydrofolic acid. S-Propanoyl [317-66-8]... 

Coenzyme A can be converted to thioesters, the active acyl-transfer agents in the cell. Of the thioesters that coenzyme A forms, the acetyl ester, called acetyl-coenzyme A and abbreviated as... 

Why are thioesters superior to ordinary esters as acyl-transfer agents Part of the answer lies in the acidity difference between alcohols and thiols (Sec. 7.1 7). Since thiols are much stronger acids than are alcohols, their conjugate bases, SR, are much weaker bases than OR. Thus, the —SR group of thioesters is a much better leaving group, in nucleophilic substitution reactions, than is the —OR group of ordinary esters. Thioesters are not so reactive that they hydrolyze in cellular fluid, but they are appreciably more reactive than simple esters. Nature makes use of this feature. 

Four important coenzymes contain nucleotides as part of their structures. We have already mentioned coenzyme A (for its structure, see page 312), which contains ADP as part of its structure. It is a biological acyl-transfer agent and plays a key role in fat metabolism. Nicotinamide adenine dinucleotide (NAD) is a coenzyme that dehydrogenates alcohols to aldehydes or ketones, or the reverse process It reduces carbonyl groups to alcohols. It consists of two nucleotides linked by the 5 hydroxyl group of each ribose unit. 

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