Acylation Of Thiols Research Articles

A Sequential Acyl Thiol-Ene and Thiolactonization Approach for the Synthesis of δ-Thiolactones.

A novel strategy for the synthesis of δ-thiolactones from inexpensive and readily available γ-unsaturated esters has been developed. This strategy incorporates a radical acyl thiol-ene reaction as the key C-S bond forming step. Cyclization is achieved via a Steglich-type thiolactonization of 5-mercaptopentanoic acids. We report the facile and scalable synthesis of δ-thiolactones in moderate to good yield under mild reaction conditions with tolerance for a range of functional groups.

Rapid Access to Thiolactone Derivatives through Radical-Mediated Acyl Thiol-Ene and Acyl Thiol-Yne Cyclization.

A new synthetic approach to thiolactones that employs an efficient acyl thiol-ene (ATE) or acyl thiol-yne (ATY) cyclization to convert unsaturated thiocarboxylic acid derivatives into thiolactones under very mild conditions is described. The high overall yields, fast kinetics, high diastereoselectivity, excellent regiocontrol, and broad substrate scope of these reaction processes render this a very useful approach for diversity-oriented synthesis and drug discovery efforts. A detailed computational rationale is provided for the observed regiocontrol.

ChemInform Abstract: Thioesters Synthesis: Recent Adventures in the Esterification of Thiols

AbstractReview: 67 refs.

ChemInform Abstract: A Simple Acylation of Thiols with Anhydrides.

AbstractVarious thiols can be easily acylated under conditions A) or B).

A simple acylation of thiols with anhydrides

Different thiols were efficiently acylated at room temperature with different anhydrides in the presence of potassium carbonate. Chemoselective protection of thiol in the presence of hydroxy group was achieved using di- tert-butyl dicarbonate and isatoic anhydride.

Controllable enzymatic Markovnikov addition and acylation of thiols to vinyl esters

The chemical selectivity between Markovnikov addition and acylation in the reaction of thiols and vinyl esters were developed. The addition reaction was efficiently catalyzed by CAL-B at 50 °C in isopropyl ether, affording the Markovnikov adducts with good yields. Acylation was carried out under the catalysis of d-amino acylase in DMF at 50 °C. A series of thioethers and thioesters were synthesized via the controllable enzymatic methods.

Thiol end-capped titanium–copper complexes: Synthesis, solid state structure and electrochemical behavior

The synthesis of acetylene, acyl–thiol and thiol end-capped titanium–copper π-tweezer complexes of the structural type {[Ti](μ-σ,π-CCR)2}CuSC6H4-4-R′ ([Ti]=(η5-C5H4SiMe3)2Ti; 3: R=SiMe3, R′=CCH; 5a: R=SiMe3, R′=SC(O)Me; 5b: R=tBu, R′=SC(O)Me), {[Ti](μ-σ,π-CCSiMe3)2}CuSC6H4–C6H4-4-SH (7) and ({[Ti](μ-σ,π-CCR)2}CuSC6H4)2 (8) is described. Homobimetallic 3, 5a and 5b are accessible via the reaction of {[Ti](μ-σ,π-CCR)2}CuMe (1a: R=SiMe3, 1b: R=tBu) with stoichiometric amounts of Me(O)CS-1-C6H4-4-CCH (2) and C6H4-1,4-(SC(O)Me)2 (4), respectively. Within these reactions the copper–sulfur bond formation is accompanied by the elimination of acetone. If 1a is treated with the dithiol (HS–C6H4)2 (6) in a ratio of 1:1 or 2:1 than dinuclear 7 and tetranuclear 8 are produced upon formation of methane. Both types of reaction allow in a straightforward manner the synthesis of analytically pure samples in high yield. In addition, complex 8 is also formed, when equimolar amounts of 7 are reacted with1a.The solid state structure of 5a is reported. This complex possesses a low-valent CuSC6H4-4-SC(O)Me entity with copper(I) in a planar surrounding. All other geometrical features are in agreement with the expected data relevant for Ti–Cu organometallic π-tweezer complexes.Cyclic voltammetric studies were carried out with 3–8. The results are discussed with respect to intramolecular interactions between the various electrochemically active reaction sites.

OXIDATIVE HYDROLYSIS OF PHOSPHORUS(V) ESTERS OF THIOLS BY PEROXYMONOSULFATE ION. REACTIONS OF PEROXYMONOSULFATE ION WITH PHOSPHORUS(V) ESTERS OF THIOLS

Peroxymonosulfate ion, HSO−5, as Oxone, readily converts phosphorus(V) esters of thiols into the phosphorus(V) and sulfonic acids. The esters were Ph2PO·SC6H4R(p) with R=MeO (1a), Me (1b), H (1c), Cl (1d) and NO2 (1e), (EtO)2PO · SPh (2), Ph2OI · SEt (3) and PhPO(OEt)SEt (4). Reactions are first order in each reactant and second-order rate constants, k2, for 1a–e fit the Hammett equation with ρ=−0.46. The rate constants increase markedly with increasing water content of H2O–MeCN, the activation enthalpies are low and the entropies are negative. Despite the low value of −ρ, these esters are much less reactive than thiol ethers, but the rate constants of reactions of these compounds and acyl thiols qualitatively follow the ionization potentials of the ethers and the esters. © 1997 John Wiley & Sons, Ltd.

Lack of asymmetry in the active sites of tetrameric D-glyceraldehyde-3-phosphate dehydrogenase during alkylation in the crystalline state

D-Glyceraldehyde-3-phosphate dehydrogenase (GPDH; EC 1.2.1.12) catalyzes the oxidative phosphorylation of D-glyceraldehyde-3-phosphate (GAP) through the formation of an acyl thiol enzyme. It is composed of 4 subunits of identical amino acid sequence (review [I]). The X-ray diffraction studies indicated that the subunit structure of crystalline GPDH from different sources 12-61, except that from Bacillus stearothermophilus [7], displays a pairwise asymmetry which may have functional consequences. In the case of lobster GPDH crystals it was also suggested that Cys-149 bearing the essential thiol group interacted with His-176 only in 2 of the 4 subunits 121. This implies that the mercaptide-imidazolium ion-pair formation between Cys149 and His176, which enhances the nucleophilicity of the thiol group below its pK, 181, is formed in 2 subunits only. Hence, it could be expected that the essential cysteine residues in the crystal may react at different rates in a simple alkylation. It has been shown that all 4 reactive sulphydryl groups of GPDH crystals could be alkylated with the negatively charged iodoacetate 191, but quantitative data on the reaction rates were not presented. mercuribenzoate [ 141 exhibit ‘half-of-the-sites’ reactivity even in solution and thus they are not suitable for studying this problem. Furthermore, with the neutral iodoacetamide, electrostatic effects which may complicate the reaction could also be eliminated. We have found that all 4 subunits of the crystalline enzyme react with iodoacetamide at identical rates and the rates of alkylation are similar in crystal and in solution.

Comportement electrochimique d'oxocarbones et d'aci-reductones en relation avec le transport d'electrons dans les processus biologiques — VI. Oxydation des esters de l'hydrovitamine K 3 en solvant non-aqueux. Application aux reactions d'acylation: synthese electrochimique de thioester

The oxidation of the esters of 2-methyl 1,4-naphthoquinol has been studied in acetonitrile solution at platinum electrode. The oxidation process, fits into the general scheme of an ECE mechanism and the coupled chemical reaction corresponds to the attack of the one-electron intermediate by the nucleophilic species present in the medium. This reaction is used for the anodic acylation of thiols to obtain the corresponding thiolesters.

Relationship between the Structures of S-Acyl Thiol Compounds and Their Rates of Hydrolysis by Pancreatic Lipase and Hepatic Carboxylic Esterase

About 100 S-fatty acyl thiol compounds designed as substrates for pancreatic lipase [EC 3.1.1.3] were synthesized and tested for susceptibility to hydrolysis by hog pancreatic lipase and hog hepatic carboxylic esterase [EC 3.1.1.1] using 5,5'-dithiobis(2-nitrobenzoic acid) as a chromogenic reagent to determine the hydrolytic rates of their S-acyl bonds. In general, the hydrolytic rates of S-acyl bonds by the lipase were fast with thioglycerol type thiol moieties, slow with dithioethyleneglycol type or monothiol type, and negligible with thiopolyol type. As for the acyl moieties, the hydrolysis of the S-acyl bonds was fast with C3-5 acyl groups, followed by C6-8 acyl groups, and the rate decreased as the acyl chain length deviated from these values or branched. On the other hand, the hydrolysis of S-acyl bonds by the esterase occurred with all types of S-acyl esters except for esters of long S-acyl chains. Of all the compounds tested with the lipase, the rate of hydrolysis of S-acyl bond was maximum with 2,3-dimercaptopropan-1-ol tributyroate [I], high with 3-mercaptopropane-1,2-diol tributyroate [II], but negligible with the analogous compound, 1,3-dimercaptopropan-2-ol tributyroate. Compounds [I] and [II] may be practically useful as substrates for lipase assay in human serum samples pretreated with phenylmethylsulfonyl fluoride, a potent inhibitor against both serum arylesterase [EC 3.1.1.2] and hepatic esterase, which attack [I] and [II].

Determination of acyl-CoA concentrations using pancreatic lipase

A rapid and sensitive assay for acyl-CoA thiol esters has been devised using pancreatic lipase as a hydrolytic agent in the presence of dithionitrobenzoic acid to detect the liberated CoA. Acyl thiol esters containing 12–22 carbon atoms and 0–6 double bonds are measurable in this system whereas acetyl-CoA and malonyl-CoA were not cleaved.

The conjugation of glutathione with unsaturated acyl thiol esters and the metabolic formation of S-carboxyalkylcysteines.

The partial purification and properties of an enzyme from the soluble fraction of rat liver that catalyses the reaction of glutathione with 2,3-unsaturated acyl thiol esters is described, and its possible role in the formation of S-carboxyalkylcysteines is discussed. The synthesis of S-(3-methylcrotonyl)- and S-(2-methylcrotonyl)-N-acetylcysteamine and of S-crotonyl-NN-dimethylcysteamine hydrochloride and dicyclohexylammonium S-crotonyl-N-acetyl-l-cysteine is described.

Electronic Structure of Lone Pairs. II. Disulfides and Acyl Thiol

Abstract The electronic structure and the electronic transition of three cyclic disulfides, (CH2)3S2, (CH2)4S2, and (CH3)2S2, are calculated by the semi-empirical ASMO SCF method in order to study the interaction of the neighbouring lone pairs of the S–S bond in connection with the ability of reductive scission. It is concluded that the absorption at 2500–3000 Å is the transition of n–σ* and that the variation in the maximum for the various cyclic disulfides and the chain disulfide are induced by the change in the dihedral angle that a molecule can take. The electronic structure and the reactivity of (CH3)2S2, CH3SSH, and CH3SCOCH3 are then discussed on the basis of an extended Hückel calculation. It is suggested that there is the possibility of an interaction between two molecules, R2S2, through the S–S bond of each molecule, in the HO of one molecule and in the LV of another.

Acylation. Part XXXIII. The spontaneous and acid-catalysed acylation of thiols by dimethylketen in diethyl ether

At 25°, in diethyl ether solution, ethanethiol and 1,1-dimethylethanethiol add spontaneously to dimethylketen at rates comparable with those found for their oxygen analogues. The observed rates are very irreproducible, but the only product is the expected thio ester. Experiments with added radicals suggests that a radical path may contribute to these spontaneous thiolyses.The addition of ethanethiol is catalysed by isobutyric acid. This reaction is analogous to acid-catalysed addition of alcohols, and is of the first order in keten, thiol, and catalyst. Similar catalysis of the addition of 1,1-dimethylethanethiol is not detectable owing to its slowness and to the preferential addition of the catalyst.

Acyl Coenzyme A:1-Alkenyl-glycero-3-phosphorylcholine Acyltransferase Action in Plasmalogen Biosynthesis

Acylation of 1-O-(1′-alk-1′-enyl)-glycero-3-phosphorylcholine by long chain acyl thiol esters of coenzyme A to form plasmalogens was catalyzed by enzymes from erythrocytes and muscle. The alkenyl acyl phosphoglycerides produced were the type of plasmalogen most commonly present in mammalian tissues. Enzymes catalyzing this reaction are located in membrane fractions that also contain acyl transfer activity for other phospholipids. Acyl transfer rates with oleoyl-, linoleoyl-, and arachidonoyl-CoA were 13, 27, and 27 mµmoles per min per mg of protein, respectively, with the acyl analogue that forms lecithin, whereas they were

Acylation. Part XX. The comparative acylation of phenols and thiols

At 40°(undissociated) 2-naphthol and p-nitrophenol are, respectively, 1·8 and 1·1 times more reactive towards acetyl chloride in acetic acid than are their thiol analogues. This result supports our predictions about the acylation of thiols. The thiols appear more easily acylated than would be predicted from their thermodynamic acidities.

Imidazole Catalysis. VI.1 The Intramolecular Nucleophilic Catalysis of the Hydrolysis of an Acyl Thiol. The Hydrolysis of n-Propyl γ-(4-Imidazolyl)-thiolbutyrate

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTImidazole Catalysis. VI.1 The Intramolecular Nucleophilic Catalysis of the Hydrolysis of an Acyl Thiol. The Hydrolysis of n-Propyl γ-(4-Imidazolyl)-thiolbutyrateThomas C. BruiceCite this: J. Am. Chem. Soc. 1959, 81, 20, 5444–5449Publication Date (Print):October 1, 1959Publication History Published online1 May 2002Published inissue 1 October 1959https://doi.org/10.1021/ja01529a048RIGHTS & PERMISSIONSArticle Views135Altmetric-Citations36LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (688 KB) Get e-Alerts Get e-Alerts