Search

Herein the one‐pot thioesterification and hydrothiolation of α, β‐unsaturated esters with aliphatic thiols was reported at room temperature. The mechanism was indirectly revealed which α, β‐unsaturated thioester was the intermediate. The advantages of this method included transition‐metal‐free, mild conditions, broad substrate scope and good functional group tolerance. On the other hand, the hydrothiolation of α, β‐unsaturated aliphatic esters at room temperature was also developed. [ABSTRACT FROM AUTHOR]

The generation of thioesters through thioesterification of carboxylic acid has significant synthetic value given the easy availability of various carboxylic acids and the extensive application of thioesters. An economical and rapid thioester synthesis approach is still needed. Herein, we achieved thioesterification of carboxylic acids with valuable glycosyl thiol, aromatic and aliphatic thiols mediated by sulfonyl fluoride (SO2F2). The compatibility of numerous carboxylic acid substrates was tested, including (hetero)aromatic and aliphatic carboxylic acids and the reaction proceeded smoothly under mild conditions at good yields. Late‐stage modification of drug molecules rac‐Naproxen and Loxoprofen proved feasible. Besides, the gram‐scale reaction demonstrated the utility of this protocol. [ABSTRACT FROM AUTHOR]

A new one‐pot solvent‐less reaction to convert benzylic, allylic, ferrocenyl or tertiary alcohols into S‐thioesters, bench‐stable and less odorous precursors of the corresponding thiols, which is based on reactions in neat thioacetic acid in the presence of tetrafluoroboric acid, is presented. Reaction monitoring by NMR and GC of the benzyl alcohol conversion indicated the intermediate formation of benzyl acetate and benzyl thionoacetate (PhCH2OC(S)CH3) prior to the slower conversion to the final S‐benzyl thioacetate product. Increasing the HBF4 concentration enhanced the reaction rate, giving good to excellent yield (up to 99 %) for a large scope of alcohols. Control experiments, with support of DFT calculations, have revealed a thermodynamically favorable, though requiring HBF4‐activation, disproportionation of CH3C(O)SH to CH3C(O)OH and CH3C(S)SH, the latter immediately decomposing to H2S and (MeC)4S6 but also generating the hitherto unreported [MeC(O)C(Me)S]2(μ‐S)2. Kinetic investigations demonstrated that the rate of benzyl alcohol conversion is second‐order in [PhCH2OH] and second order in [HBF4], while the rate of conversion of the benzyl acetate intermediate to S‐benzyl thioacetate is second order in [PhCOOMe] and fourth order in [HBF4]. The DFT calculations rationalize the need to two alcohol molecules and two protons to generate the reactive benzyl cation. [ABSTRACT FROM AUTHOR]

An effective and practical synthesis of α‐ketothioesters has been reported for direct oxidative thioesterification of substitutional acetophenones with dimethyl sulfoxide and iodine in the presence of boric acid and acetic anhydride in high yields. According to the control experiments and literatures, the reaction mechanism was proposed to undergo via Pummerer rearrangement. [ABSTRACT FROM AUTHOR]

A simple and efficient method has been developed for the synthesis of thioesters from carboxylic acids and thiols using N,N'-diisopropylcarbodiimide (DIC). The reactions were carried out in water as an environmentally friendly and green solvent. The developed procedure presents an economic, efficient, mild, and very simple protocol for thioesterification reaction in aqueous media. [ABSTRACT FROM AUTHOR]

The direct nucleophilic addition to amides represents an attractive methodology in organic synthesis that tackles amidic resonance by ground-state destabilization. This approach has been recently accomplished with carbon, nitrogen and oxygen nucleophiles. Herein, we report an exceedingly mild method for the direct thioesterification and selenoesterification of amides by selective N–C(O) bond cleavage in the absence of transition metals. Acyclic amides undergo N–C(O) to S/Se–C(O) interconversion to give the corresponding thioesters and selenoesters in excellent yields at room temperature via a tetrahedral intermediate pathway (cf. an acyl metal). [ABSTRACT FROM AUTHOR]

We report two methods for the preparation of peptide thioesters containing Tyr(SO 3 H) residue(s), without use of a protecting group for the sulfate moiety. The first was based on direct thioesterification using carbodiimide on a fully protected peptide acid, prepared on a 2-chlorotrityl (Clt) resin with fluoren-9-ylmethoxycarbonyl (Fmoc)-based solid-phase peptide synthesis (Fmoc-SPPS). Subsequent deprotection of the protecting groups with trifluoroacetic acid (TFA) (0 °C, 4 h) yielded peptide thioesters containing Tyr(SO 3 H) residue(s). Peptide thioesters containing one to three Tyr(SO 3 H) residue(s), prepared by this method, were used as building blocks for the synthesis of the N α -Fmoc-protected N-terminal part of P-selectin glycoprotein ligand 1 (PSGL-1) (Fmoc-PSGL-1(43-74)) via silver-ion mediated thioester segment condensation. The other method was based on the thioesterification of peptide azide, derived from a peptide hydrazide prepared on a NH 2 NH-Clt-resin with Fmoc-SPPS. Peptide thioester containing two Tyr(SO 3 H) residues, prepared via this alternative method, was used as a building block for the one-pot synthesis of the N-terminal extracellular portion of CC-chemokine receptor 5 (CCR5(9-26)) by native chemical ligation (NCL). The two methods for the preparation of peptide thioesters containing Tyr(SO 3 H) residue(s) described herein are applicable to the synthesis of various types of sulfopeptides.

Unique tunable aryl imidazolium ionic liquids successfully catalyzed Friedel−Crafts acylation and thioesterification in sealed tubes. These reactions can form a C−C bond and a C−S bond with high atom economy. Ionic liquids exhibited high activity and catalyzed essential reactions with good to excellent yields while retaining their catalytic activities for recycling.

The main objective of the present study was to synthesize potential inhibitor/activators of AChE and hCA I-II enzymes, which are thought to be directly related to Alzheimer's disease. Dithiodibenzothioate compounds were synthesized by thioesterification. Six different thiolate compounds produced were characterized by 1 H-, 13 C-NMR, FT-IR, LC-MS/MS methods. HOMO-LUMO calculations and electronic properties of all synthesized compounds were comprehensively illuminated with a semi-empirical molecular orbital (SEMO) package for organic and inorganic systems using Austin Model 1 (AM1)-Hamiltonian as implemented in the VAMP module of Materials Studio. In addition, the inhibition effects of these compounds for AChE and hCA I-II in vitro conditions were investigated. It was revealed that TE-1, TE-2, TE-3, TE-4, TE-5, and TE-6 compounds inhibited the AChE under in vitro conditions. TE-1 compound activated the enzyme hCA I while TE-2, TE-3 TE-4 compounds inhibited it. TE-5 and TE-6, on the other hand, did not exhibit a regular inhibition profile. Similarly, TE-1 activated the hCA II enzyme whereas TE-2, TE-3, TE-4, and TE-5 compounds inhibited it. TE-6 compound did not have a consistent inhibition profile for hCA II. Docking studies were performed with the compounds against AChE and hCA I-II receptors using induced-fit docking method. Molecular Dynamics (MD) simulations for best effective three protein-ligand couple were conducted to explore the binding affinity of the considered compounds in semi-real in-silico conditions. Along with the MD results, TE-1-based protein complexes were found more stable than TE-5. Based on these studies, TE-1 compound could be considered as a potential drug candidate for AD.Communicated by Ramaswamy H. Sarma.

Development of the highly active and stable heterogeneous transition metal catalysts is of great importance in synthetic chemistry. Herein, zeolite Beta nanoparticles assembled Cu catalyst (Cu-Beta-Nano) with high external surface area was directly synthesized, and it exhibits excellent catalytic activity and good recyclability in cross-coupling of aldehydes and disulfides for synthesis of thioesters. The high activity and good recyclability of the Cu-Beta-Nano catalyst should be attributed to the high external surface area of the catalyst and highly dispersed active copper species in the zeolite. [ABSTRACT FROM AUTHOR]

Poly(3,4-dimethyl-5-vinylthiazolium) was synthesized from 3,4-dimethyl-5-vinylthiazole through free radical polymerization and was examined as polymer precatalysts in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) for the thioesterification of aldehydes with thiols. The poly(5-vinylthiazolium)/DBU had excellent catalytic activity and could be reused 10 times without a considerable loss of activity. [ABSTRACT FROM AUTHOR]

The influence of Jeffamine T-403 polyoxypropylenetriamine on the physico-mechanical, adhesion, and relaxation properties of polymeric compositions based on the products of preliminary thioesterification reaction of epoxy resin with liquid thiokol was studied. It was shown that the introduction of polyoxypropylenetriamine leads to a significant increase of the adhesive and cohesive strength, the elongation at break, and the work of destruction of the material. [ABSTRACT FROM AUTHOR]

The first organo-catalyzed silylthioesterification of a carboxylic acid and a commercially available mercaptoorganosilane results in the in situ production of an O -silylthionoester. Subsequent amine addition forms amides in an operationally simple one-pot procedure without removal of water. The scope and efficiency of these reactions with respect to the catalyst, carboxylic acid, amine, [Si–S] moiety, and solvent are investigated. A number of functionalities are tolerated in the two-step amidation including alkene, alkyne, alkyl and aryl halides, benzylic ethers, and heterocycles with free coordinating sites. [ABSTRACT FROM AUTHOR]

An amine-catalyzed, one-pot synthesis of thioesters directly from carboxylic acids, thioureas, and Michael acceptors is described. This process was further improved by use of 1-[2-(methylamino)ethyl]-3-phenylthiourea ( 4) as the catalyst. Aromatic and aliphatic carboxylic acids with functional groups are compatible with this process, and both α,β-unsaturated esters and ketones can be the Michael acceptors for this reaction. The progress of this reaction was monitored by 1H NMR, and a reaction mechanism is proposed. [ABSTRACT FROM AUTHOR]

Nonribosomal peptide synthetases are large, multi-domain enzymes that produce peptide molecules with important biological activity such as antibiotic, antiviral, anti-tumor, siderophore and immunosuppressant action. The adenylation (A) domain catalyzes two reactions in the biosynthetic pathway. In the first reaction, it activates the substrate amino acid by adenylation and in the second reaction it transfers the amino acid onto the phosphopantetheine arm of the adjacent peptide carrier protein (PCP) domain. The conformation of the A domain differs significantly depending on which of these two reactions it is catalyzing. Recently, several structures of A–PCP di-domains have been solved using mechanism-based inhibitors to trap the PCP domain in the A domain active site. Here, we present an alternative strategy to stall the A–PCP di-domain, by engineering a disulfide bond between the native amino acid substrate and the A domain. Size exclusion studies showed a significant shift in apparent size when the mutant A–PCP was provided with cross-linking reagents, and this shift was reversible in the presence of high concentrations of reducing agent. The crosslinked protein crystallized readily in several of the conditions screened and the best crystals diffracted to ≈8 Å. [ABSTRACT FROM AUTHOR]

Peptides having the C-terminal N -alkylcysteine (NAC) with a free carboxy group, which can be easily prepared by the conventional 9-fluorenylmethoxycarbonyl (Fmoc) solid-phase peptide synthesis (SPPS), was directly used for the native chemical ligation (NCL) based on the in situ thioesterification method. The reaction efficiently proceeded under a mild acidic condition (pH ∼5) to give the ligated product. This method was successfully used for the synthesis of the human brain natriuretic peptide, (BNP)-32, showing the usefulness of the peptidyl NAC as a thioester surrogate for the NCL reaction. [ABSTRACT FROM AUTHOR]

A novel alkynyl-containing disulfide compound, 5,8-dihydro-1H,4H-2,3,6,7-tetrathia-anthracen (TMSEDTTA), was synthesized. The structures of the target compound and the intermediates have been identified by1H NMR,13C NMR, mass spectrometry, Fourier-transform infrared, Raman spectra, x-ray photoelectron spectroscopy, and elemental analysis. In addition, the structure of (Z)-(1,2-dibromo-2-(2,3,5,6-tetrakis(bromomethyl)phenyl)vinyl)trimethylsilane(5)was determined by single x-ray analysis. [Supplementary materials are available for this article. Go to the publisher's online edition ofSynthetic Communications®for the following free supplemental resource(s): Full experimental and spectral details.] [ABSTRACT FROM AUTHOR]

Human glycodelin consists of 162 amino acid residues and two N-linked glycans at Asn28 and Asn63. In this study, we synthesized it by a fully convergent strategy using native chemical ligation (NCL) in N to C direction. The four peptide segments corresponding to 1-31, 32-65, 66-105 and 106-162 sequences were synthesized by 9-fluorenylmethoxycarbonyl based solid-phase peptide synthesis. At the C-terminus of the second segment, N-ethyl- S-acetamidomethyl-cysteine was attached as a post-ligation thioesterification device. The N-terminal two segments were condensed by the homocysteine-mediated NCL at Leu-Met site, and the product was methylated to convert homocysteine to methionine. After deprotection of acetamidomethyl group on the N-ethylcysteine residue, the peptide was thioesterified by N-alkylcysteine-assisted method. The product was then ligated with the C-terminal half, which was obtained by the NCL of third and fourth segments, to give the full-length glycodelin. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A metal-free, tetraethylammonium bromide-catalyzed oxidative coupling of aldehydes or alcohols with thiophenols or disulfides has been developed. This protocol affords an efficient and inexpensive approach to the synthesis of a wide range of thioesters in high yields. [ABSTRACT FROM AUTHOR]

Thioesterification can be realized via an odorless, one-pot reaction through the in situ generation of S-alkylisothiouronium salts from organic halides and thiourea in aqueous Triton X-100 (TX100) micelles. The protocol is free of foul-smell thiols and organic solvents, and operates under mild conditions, thereby offering considerable potential for applications in organic synthesis. [ABSTRACT FROM AUTHOR]

Here we report the synthesis and utility of ethyl 2-( tert-butoxycarbonyloxyimino)-2-cyanoacetate (Boc-Oxyma) as an efficient coupling reagent for racemization-free esterification, thioesterification, amidation reactions and peptide synthesis that uses equimolar amounts of acids and alcohols, thiols, amines or amino acids, respectively. Its application to solid phase as well as solution phase peptide synthesis is also demonstrated and a mechanistic investigation is discussed. Boc-Oxyma is similar to the well known coupling agent COMU {1-[1-cyano-2-ethoxy-2-oxoethylideneaminooxy)-dimethylaminomorpholino]uronium hexafluorophosphate} in terms of its high reactivity and mechanism of action. However, it is not only much easier to prepare, but also to recover and reuse, thereby generating far less chemical waste. [ABSTRACT FROM AUTHOR]

Abstract: Acyl-CoA synthetases belong to the superfamily of adenylate-forming enzymes, and catalyze the two-step activation of fatty acids or carboxylate-containing xenobiotics. The carboxylate substrate first reacts with ATP to form an acyl-adenylate intermediate, which then reacts with CoA to produce an acyl-CoA ester. Here, we report the first crystal structure of a medium-chain acyl-CoA synthetase ACSM2A, in a series of substrate/product/cofactor complexes central to the catalytic mechanism. We observed a substantial rearrangement between the N- and C-terminal domains, driven purely by the identity of the bound ligand in the active site. Our structures allowed us to identify the presence or absence of the ATP pyrophosphates as the conformational switch, and elucidated new mechanistic details, including the role of invariant Lys557 and a divalent magnesium ion in coordinating the ATP pyrophosphates, as well as the involvement of a Gly-rich P-loop and the conserved Arg472-Glu365 salt bridge in the domain rearrangement. [Copyright &y& Elsevier]

2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-(Z)-methoxyiminoacetic acid 2-benzothiazolyl thioester(III), an important intermediate of the fourth generation cephalosporins, was efficiently synthesized by reacting 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(Z)-methoxyiminoacetic acid (I) with 2,2′-dibenzothiazole disulfide (II) in the presence of triphenylphosphine. Effects of reaction time, temperature, solvents, catalysts and feeding molar ratio on the yield and quality of products were investigated, and an improved procedure suitable for industrial production was established. Using 1,2-dichloroethane as solvent, triphenylphosphine as reducer, and triethylamine as catalyst, n(I): n(II): n(triphenylphosphine)51.0: 1.0: 1.0, the product was obtained at room temperature in 98.1% yield. The purity of the product without further purification is 98.7% determined by HPLC method. This procedure could be a suitable alternative to the traditional processes because of its easy handling, high yield and low cost. [ABSTRACT FROM AUTHOR]

A novel trisulfide-containing thiophene, 1,5-dihydrothieno[3,4-e][1,2,3]trithiepine (5), and a disulfide analogue, 1,4-dihydrothieno[3,4-d][1,2]dithiine (4), were designed and synthesized. All the compounds were characterized by FT-IR, NMR, Raman, MS, and elemental analysis, some of which were confirmed by single-crystal structure analysis. The designed molecules have potential usage as the cathode material for batteries. [ABSTRACT FROM AUTHOR]

A novel disulfide-containing aniline, 5,8-dihydro-1H,4H-2,3,6,7-tetrathia-anthracen-9-ylamine (6) was synthesized. The structures of the target compound and the intermediates have been identified by ¹H NMR, MS, IR, Raman and elemental analysis. In addition, the structure of 9-Nitro-5,8-dihydro-1H,4H-2,3,6,7-tetrathia-anthracene (5) was determined by single X-ray analysis. [ABSTRACT FROM AUTHOR]

Peptides bearing C-terminal thioester and selenoester functionalities are essential precursors for the chemical synthesis of larger proteins using ligation chemistry, including native chemical ligation (NCL) and diselenide-selenoester ligation (DSL). The use of a side-chain anchoring thioesterification or selenoesterification approach offers a robust method to access peptide thioesters or peptide selenoesters in excellent yields and in high purity. Importantly, this methodology overcomes solubility issues and epimerization of the C-terminal amino acid residue that can occur using solution-phase approaches. Detailed methods for the solid-phase synthesis of peptide thioesters and selenoesters using a side-chain anchoring approach are outlined in this article., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Palmitic acid hexadecylthioester and other long-chain acyl thioesters have been prepared in high yield (80–85%, purity >98%) by solvent-free lipase-catalyzed thioesterification of fatty acids with alkanethiols in vacuo. A lipase B preparation from Candida antarctica was more effective than a lipase preparation from Rhizomucor miehei and, particularly, those from papaya latex and porcine pancreas. Lipase-catalyzed transthioesterification of fatty acid methyl esters with alkanethiols was less effective than thioesterification for the preparation of acyl thioesters. However, in transthioesterification, a lipase preparation from R. miehei was more effective than a lipase B preparation from C. antarctica. Lipases from papaya latex and porcine pancreas led to moderate conversions to acyl thioesters in both thioesterification and transthioesterification reactions, whereas only small proportions of thioesters were formed using lipase from Rhizopus arrhizus. Lipases from Chromobacterium viscosum and Candida rugosa were not effective at all. [ABSTRACT FROM AUTHOR]

Unique tunable aryl imidazolium ionic liquids successfully catalyzed Friedel–Crafts acylation and thioesterification in sealed tubes. These reactions can form a C−C bond and a C−S bond with high atom economy. Ionic liquids exhibited high activity and catalyzed essential reactions with good to excellent yields while retaining their catalytic activities for recycling. [ABSTRACT FROM AUTHOR]

Proteins incorporating artificial moieties such as fluorophores and drugs have enjoyed increasing use in chemical biology and drug development research. Preparation of such artificial protein derivatives has relied mainly on native chemical ligation in which peptide/protein thioesters chemoselectively react with N-terminal cysteine (Cys) peptides to afford protein molecules. The protein thioesters derived from expressed proteins represent thioesters that are very useful for the preparation of artificial proteins by native chemical ligation with synthetic peptides with N-terminal Cys. We recently have developed a traceless thioester-producing protocol using carboxypeptidase Y (CPaseY) which is compatible with an expressed protein. The traceless character is ensured by CPaseY-mediated hydrazinolysis of C-terminal Xaa (X)-Cys-proline (Pro)-leucine (Leu)-OH sequence followed by an auto-processing of the Cys-Pro (CP) dipeptide unit, affording the corresponding X-thioester (X-SR). However, hydrazinolysis of the amide bond in the prolyl leucine junction depends significantly on the nature of X. In the case of hydrophobic X residues, the hydrazinolysis overreacts to give several hydrazides while the reaction of hydrophilic X residues proceeds slowly. In this research, we attempted to develop an X-independent CPaseY-mediated protocol and found that the incorporation of a triple CP sequence into the C-terminal end (X-(CP) 3 -Leu-OH) allows for efficient X-SR formation in a manner that is independent of X.

Long-chain fatty acyl-CoA synthetases (ACS) are a family of essential enzymes of lipid metabolism, activating fatty acids by thioesterification with coenzyme A. Fatty acyl-CoA molecules are then readily utilized for the biosynthesis of storage and membrane lipids, or for the generation of energy by ß-oxidation. Acyl-CoAs also function as transcriptional activators, allosteric inhibitors, or precursors for inflammatory mediators. Recent work suggests that ACS enzymes may drive cellular fatty acid uptake by metabolic trapping, and may also regulate the channeling of fatty acids towards specific metabolic pathways. The implication of ACS enzymes in widespread lipid associated diseases like type 2 diabetes has rekindled interest in this protein family. Here, we describe in detail how to measure long-chain fatty acyl-CoA synthetase activity by a straightforward radiometric assay. Cell lysates are incubated with ATP, coenzyme A, Mg(2+), and radiolabeled fatty acid bound to BSA. Differential phase partitioning of fatty acids and acyl-CoAs is exploited to quantify the amount of generated acyl-CoA by scintillation counting. The high sensitivity of this assay also allows the analysis of small samples like patient biopsies.