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The first synthetic strategy for nonsymmetrical 3,3″-biflavones is described. To this end, a novel visible-light iridium-catalyzed radical C-3 alkylation of flavones with

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We report a 1,2-migration (aryl dance reaction) of the aryl group on heteroles. AlCl

Enzymatic lipophilization has been proposed as a cost-effective strategy to produce new liposoluble antioxidant compounds. In this study, modified oils rich in structured phenolipids were prepared via one-pot enzymatic acylation of hydroxytyrosol (HTYR), vanillyl alcohol (VA) and homovanillyl alcohol (HVA) with pomace olive oil (POO) in solvent-free conditions using immobilized lipase on biogenic nanoparticles. The effect of temperature (30–70 °C) and enzyme concentration (0.1–1%, w/w) on the efficiency of the bioprocess as well as the reusability of the nanobiocatalyst were thoroughly investigated. The modified oils exhibited increased antioxidant activity compared to the control oil according to DPPH and CUPRAC assays (p < 0.05). The oxidative stability of pomace olive oil was also significantly enhanced after modification, as depicted by the K232 values and TBARS contents under accelerated oxidation at 60 °C (p < 0.05). Moreover, a fortified mayonnaise containing modified oil with HTYR was prepared that was noticeably stable compared to the control mayonnaise at 28 °C for 5 months (p < 0.05). Enzymatically modified oils have great potential for application in the nutraceutical and food industry, encouraging the exploitation of immobilized lipases as effective and green catalytic tools.

Väitekirja elektrooniline versioon ei sisalda publikatsioone, Asa-peptiidid on peptiidi analoogid, mis lagunevad elusorganismis aeglasemalt ja on seetõttu paljulubavad ravimikandidaadid. Nende bioaktiivsete omaduste laiemat uurimist takistavad aga asa-peptiidsideme sünteesil ilmnevad probleemid, eelkõige madal saagis ja aeglane reaktsioon. Reaktsiooni kineetiliste parameetrite määramine on üheks võimaluseks eksperimentaalselt hinnata amino- ja asa-aminohapete N-terminaalse aminorühma reaktsioonivõime erinevust ning uurida tahkefaasi peptiidsünteesi protokolli sobivust asa-peptiidsideme moodustamiseks. Tulemustest selgus, et tavalist tahkefaasi peptiidsünteesi protokolli ei saa rakendada otseselt asa-peptiidsünteesis. Asa-peptiidsideme reaktsiooni mõjutavad nii kasutatava aktivaatori efektiivsus kui ka aminohappe ja asa-aminohappe kõrvalahela steeriline efekt. Seega on vajalik asa-peptiidide sünteesimeetodeid arendada suunas, mis võimaldaks asa-aminohappe N-terminaali efektiivsemat atsüülimist. See on oluline automatiseeritud asa-peptiidide sünteesimeetodite loomiseks, mis omakorda annaks võimaluse nende ühendite bioaktiivsuse laiaulatuslikumateks uuringuteks., Aza-peptides are peptide analogues that degrade more slowly in the living organisms and are therefore promising drug candidates. However, the problems encountered in the synthesis of the aza-peptide bond, especially the low yield and slow reaction, hinder the wider investigation of their bioactive properties. Determining the kinetic parameters of the reaction is one way to experimentally evaluate the difference in the reactivity of the N-terminal amino group of amino and aza-amino acids and to study the suitability of the solid-phase peptide synthesis protocol for aza-peptide bond formation. Performed kinetic studies showed that standard solid-phase peptide synthesis protocol cannot be applied directly to aza-peptide synthesis. The reaction of the aza-peptide bond is influenced by the effectiveness of the activator used as well as the steric effect of the side chain of the amino acid and the aza-amino acid. Therefore, it is necessary to develop the synthesis methods for aza-peptides in a direction that would enable more effective acylation of the N-terminal of the aza-amino acid. This is important for the creation of automated aza-peptide synthesis methods, which in turn would provide an opportunity for more comprehensive studies of the bioactivity of these compounds., https://www.ester.ee/record=b5558662

Ketones serve as one of the most critical building blocks in organic synthesis, involving numerous functional group transformations. Herein, we report an unprecedented photoredox–nickel metallaphot...

Herein, we report the first enantioselective total synthesis of the highly complex hamigeran diterpenoid (-)-hamigeran F and its rearrangement product. The synthetic strategy features key steps of asymmetric hydrogenation, Horner-Wadsworth-Emmons olefination, and intramolecular Friedel-Crafts acylation to construct the [6,6,5]-tricyclic skeleton bearing three consecutive stereocenters, a sequence of steps involving Rosenmund reduction, Wittig reaction, dihydroxylation to assemble the α-acetoxy ketone group, and an intramolecular aldol reaction to build the tetracyclic core structure.

S-acylation is the addition of a fatty acid to a cysteine residue of a protein. While this modification may profoundly alter protein behaviour, its effects on the function of plant proteins remains poorly characterized, largely as a result of the lack of basic information regarding which proteins are S-acylated and where in the proteins the modification occurs. To address this gap in our knowledge, we used an optimized acyl-resin-assisted capture assay to perform a comprehensive analysis of plant protein S-acylation from six separate tissues. In our high- and medium-confidence groups, we identified 1,849 cysteines modified by S-acylation, which were located in 1,640 unique peptides from 1,094 different proteins. This represents around 6% of the detectable Arabidopsis proteome and suggests an important role for S-acylation in many essential cellular functions including trafficking, signalling and metabolism. To illustrate the potential of this dataset, we focus on cellulose synthesis and confirm the S-acylation of a number of proteins known to be involved in cellulose synthesis and trafficking of the cellulose synthase complex. In the secondary cell walls, cellulose synthesis requires three different catalytic subunits (CESA4, CESA7 and CESA8) that all exhibit striking sequence similarity and are all predicted to possess a RING-type zinc finger at their amino terminus composed of eight cysteines. For CESA8, we find evidence for S-acylation of these cysteines that is incompatible with any role in coordinating metal ions. We show that while CESA7 may possess a RING-type domain, the same region of CESA8 appears to have evolved a very different structure. Together, the data suggest that this study represents an atlas of S-acylation in Arabidopsis that will facilitate the broader study of this elusive post-translational modification in plants as well as demonstrating the importance of further work in this area.

Bicyclo[1.1.1]pentanes (BCPs) are widely utilized in drug design as sp

Research background. Anthocyanins possess valuable health-promoting activities with significant health benefits for humans. However, their instability is a limiting factor for their usage in functional foods and beverages. Experimental approach. In this work, a new method to enhance the stability of anthocyanins from mulberry fruit through acylation by using succinic acid as a selected acyl donor was explored. The Box-Behnken design of response surface methodology was applied to determine the optimized conditions for the acylation process. Results and conclusions. The highest acylation conversion rate was 79.04% at anthocyanins to succinic acid mass ratio 1:8.96, acylation duration 3 h and temperature 50 °C. Structural analysis of acylated anthocyanins revealed that succinic acid introduces a C-O-C bond and a hydroxyl group. The thermostability and light stability of mulberry anthocyanins were significantly improved after acylation, and the antioxidant activity expressed as total reducing power and Fe2+-chelating capacity of the acylated anthocyanins was also enhanced. Novelty and scientific contribution. Succinic acid acylation provides a novel method for stabilizing mulberry anthocyanins, as evidenced by the increased stability and antioxidant ability of anthocyanins, and thus facilitates its use in the food and nutraceutical industries., Pozadina istraživanja. Antocijani imaju pozitivni učinak na ljudsko zdravlje, no njihova im nestabilnost ograničava uporabu u proizvodnji funkcionalne hrane i pića. Eksperimentalni pristup. U ovom je radu ispitana nova metoda povećanja stabilnosti antocijana iz ploda duda aciliranjem s jantarnom kiselinom kao donorom acilne skupine. Optimalni uvjeti reakcije određeni su pomoću Box-Behnkenovog statističkog plana i metodom odzivnih površina. Rezultati i zaključci. Najveći postotak konverzije od 79,04 % postignut je pri masenom omjeru antocijana i jantarne kiseline od 1:8,96; trajanju acilacije od 3 h i temperaturi od 50 °C. Analizom strukture aciliranih antocijana utvrđeno je da sadržavaju C-O-C vezu i hidroksilnu skupinu iz jantarne kiseline. Aciliranje je bitno povećalo stabilnost antocijana pri izlaganju povišenim temperaturama i svjetlosti, te njihovu antioksidacijsku aktivnost, izraženu kroz ukupnu reducirajuću snagu i sposobnost keliranja Fe2+ iona. Novina i znanstveni doprinos. Aciliranje jantarnom kiselinom predstavlja novu metodu stabilizacije antocijana iz duda, što potvrđuje njihova povećana stabilnost i antioksidacijska sposobnost, čime je olakšana njihova primjena u proizvodnji hrane i nutraceutika.

Herein we report a nickel-catalyzed asymmetric two-component reductive aryl-acylation and aryl-carbamoylation of aryl-iodide-tethered unactivated alkenes, which utilize ortho-pyridinyl esters and i...

Sulfonic-containing UiO-66 and MIL-101 MOF materials, prepared by direct synthesis with a sulfonic acid-including benzene dicarboxylate (SO3H-BDC) linker, have been evaluated as acid catalysts in Friedel–Crafts acylation of anisole with acetic anhydride. The catalytic activity of these materials was compared to other conventional acidic sulfonic heterogeneous catalysts, such as commercial Nafion-SAC-13 and Amberlyst-15. The catalytic performance of MOF materials was significantly dependent on their textural properties and the availability of sulphonic acid groups. MIL-101-SO3H material displayed a remarkable anisole conversion and specific activity per sulfonic acid centre due to its open structure and multimodal pore size distribution. The inherent properties of MIL-101-SO3H material allowed a more sustainable catalyst regeneration than those used for conventional heterogeneous catalysts due to the deposition of reagents and products, in particular poly-acetylated compounds. MIL-101-SO3H proved an easy recovery and reusability in successive runs without any loss of activity. These promising results evidenced the potential of MIL-101-SO3H as an alternative catalyst for acid-catalyzed reactions.

A simple approach for the intramolecular aroylation of electron-rich arenes under mild conditions has been developed. A pH-controlled polarity umpolung strategy can be used to synthesize different fluorenones, which are important building blocks for biological applications. Unlike previous acylation reactions involving nucleophilic aroyl radicals, this approach likely relies on in situ generated electrophilic aroyl radicals. Detailed mechanistic and computational investigations provide detailed insights into the reaction mechanism and support the hypothesis of a pH-mediated umpolung.

Breast cancer represents the most lethal malignancy that threatens the health of females. Metastasis is the fatal hallmark of breast cancer, and current effective therapeutic targets of metastasis are still lacking. Aberrant O-GalNAcylation, which is attributed to alteration of polypeptide N-acetylgalactosaminyl transferases (GALNTs), has been implicated in cancer metastasis. However, GALNTs that drive metastasis in breast cancer and their underlying mechanisms are largely unclear. In the present study, a negative correlation between GALNT8 and the prognosis of breast cancer patients was observed in multiple groups of Gene Expression Omnibus (GEO) datasets. We then constructed a stable GALNT8 knockdown MCF7 cell line and performed transcriptome analysis using RNA sequencing, which revealed that the expression of multiple migration-related genes was changed. GALNT8 was identified as a regulator of epithelial-mesenchymal transition (EMT) markers, including E-cadherin, N-cadherin, ZO-1 and vimentin. Moreover, loss- and gain-of-function GALNT8 assays demonstrated that this glycosyltransferase inhibited the metastatic potential of breast cancer cells. Interestingly, the O-GalNAcylation of EGFR, which is the key factor related to the metastasis cascade, was impacted by GALNT8. Furthermore, our results suggested that the GALNT8-mediated O-GalNAcylation led to the suppression of the EGFR signaling pathway and metastatic potential in breast cancer cells. These results suggested that GALNT8 acts as a tumor suppressor, represses tumor metastasis and inhibits the EMT process through the EGFR signaling pathway. This finding may provide insight into the mechanism by which aberrant O-glycosylation modulates breast cancer metastasis.

The covalent grafting of alkyl gallates onto pectin using a lipase-catalyzed reaction in a tetrahydrofuran/aqueous medium process acylated pectin molecules with excellent antioxidant and antibacterial properties. The alkyl gallates including methyl, ethyl, and propyl gallates were enzymatically grafted onto pectin molecule, in order to study the effect of alkyl gallates on the functional modification of pectin. The grafting mechanism was analyzed by ultraviolet-visible spectrum (UV-Vis), Fourier transform infrared spectrum (FTIR), proton nuclear magnetic resonance (

Acyl glucuronide (AG) metabolites of carboxylic acid-containing drugs and products of their transformations have long been implicated in drug-induced liver injury (DILI). To inform on the DILI risk arising from AG reactive intermediates, a comprehensive mechanistic study of enzyme-independent AG rearrangements using nuclear magnetic resonance (NMR) and density functional theory (DFT) was undertaken. NMR spectroscopy was utilized for structure elucidation and kinetics measurements of nine rearrangement and hydrolysis products of 1β-O-acyl glucuronide of ibufenac. To extract rate constants of rearrangement, mutarotation, and hydrolysis from kinetic data, 11 different kinetic models were examined. Model selection and estimated rate constant verification were supported by measurements of H/D kinetic isotope effects. DFT calculations of ground and transition states supported the proposed kinetic mechanisms and helped to explain the unusually fast intramolecular transacylation rates found for some of the intermediates. The findings of the current study reinforce the notion that the short half-life of parent AG and slow hydrolysis rates of AG rearrangement products are the two key factors that can influence the

Prolactin-releasing peptide (PrRP) is an endogenous neuropeptide involved in appetite regulation and energy homeostasis. PrRP binds with high affinity to G-protein coupled receptor 10 (GPR10) and with lesser activity towards the neuropeptide FF receptor type 2 (NPFF2R). The present study aimed to develop long-acting PrRP31 analogues with potent anti-obesity efficacy. A comprehensive series of C18 lipidated PrRP31 analogues was characterized in vitro and analogues with various GPR10 and NPFF2R activity profiles were profiled for bioavailability and metabolic effects following subcutaneous administration in diet-induced obese (DIO) mice. PrRP31 analogues acylated with a C18 lipid chain carrying a terminal acid (C18 diacid) were potent GPR10-selective agonists and weight-neutral in DIO mice. In contrast, acylation with aliphatic C18 lipid chain (C18) resulted in dual GPR10-NPFF2R co-agonists that suppressed food intake and promoted a robust weight loss in DIO mice, which was sustained for at least one week after last dosing. Rapid in vivo degradation of C18 PrRP31 analogues gave rise to circulating lipidated PrRP metabolites maintaining dual GPR10-NPFF2R agonist profile and long-acting anti-obesity efficacy in DIO mice. Combined GPR10 and NPFF2R activation may therefore be a critical mechanism for obtaining robust anti-obesity efficacy of PrRP31 analogues.

Crop domestication has resulted in nutrient losses, so evaluating the reshaping of phytonutrients is crucial for improving nutrition. Soybean is an ideal model due to its abundant phytonutrients and wild relatives. In order to unravel the domestication consequence of phytonutrients, comparative and association analyses of metabolomes and antioxidant activities were performed on seeds of six wild (Glycine soja (Sieb. and Zucc.)) and six cultivated soybeans (Glycine max (L.) Merr.). Through ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS), we observed a greater metabolic diversity in wild soybeans, which also displayed higher antioxidant activities. (−)-Epicatechin, a potent antioxidant, displayed a 1750-fold greater abundance in wild soybeans than in cultivated soybeans. Multiple polyphenols in the catechin biosynthesis pathway were significantly higher in wild soybeans, including phlorizin, taxifolin, quercetin 3-O-galactoside, cyanidin 3-O-glucoside, (+)-catechin, (−)-epiafzelechin, catechin–glucoside, and three proanthocyanidins. They showed significant positive correlations with each other and antioxidant activities, indicating their cooperative contribution to the high antioxidant activities of wild soybeans. Additionally, natural acylation related to functional properties was characterized in a diverse range of polyphenols. Our study reveals the comprehensive reprogramming of polyphenolic antioxidants during domestication, providing valuable insights for metabolism-assisted fortification of crop nutrition.

To address the global challenge of emerging antimicrobial resistance, the hitherto most successful strategy to new antibiotics has been the optimization of validated natural products; most of these efforts rely on semisynthesis. Herein, we report the semisynthetic modification of amidochelocardin, an atypical tetracycline obtained via genetic engineering of the chelocardin producer strain. We report modifications at C4, C7, C10 and C11 by the application of methylation, acylation, electrophilic substitution, and oxidative C-C coupling reactions. The antibacterial activity of the reaction products was tested against a panel of Gram-positive and Gram-negative pathogens. The emerging structure-activity relationships (SARs) revealed that positions C7 and C10 are favorable anchor points for the semisynthesis of optimized derivatives. The observed SAR was different from that known for tetracyclines, which underlines the pronounced differences between the two compound classes.

We demonstrated recently that organocatalysts, based on a nucleophilic core (N-alkylimidazole or 4-aminopyridine) and decorated with an extensive secondary-sphere envelope (connected to the core through a benzyl substituent), strongly affect the site selectivity in acylation and phosphorylation of amphiphilic diols, sometimes entirely overriding the innate predisposition of the substrate. Preliminary studies pointed out that, despite some similarities, there are differences between the two transformations, regarding the influence of various catalyst features on the selectivity. To fully elucidate this, extended families of organocatalysts of the said design were examined, activity- and selectivity-wise, in the abovementioned transformations of model alcohol and amphiphilic diol substrates. A comparison of the influence of the catalyst design on the two reactions revealed that while the inductive electron donation of the o,o-dialkoxybenzyl substituent of the core, combined with the catalytic intermediate-stabilizing influence of some of the secondary-sphere components, causes an increase in the catalyst activity in both reactions and in the site selectivity in phosphorylation, its effect on the site selectivity in acylation is opposite. On the other hand, the lipophilicity of the secondary-sphere appendages improves the apolar site-favoring selectivity in both reactions. Thus, both factors work in concert in phosphorylation, but in opposite directions in acylation.

An unprecedented strategy for the acetylation of alcohols and amines using diacetyl as both an acylation reagent and a photosensitizer was well developed.

We developed a direct C–H bond acylation of anilines to obtain the desired 2-aminobenzophenone structures using ruthenium catalyst. The reaction proceeded smoothly under mild conditions, with good functional group tolerance and moderate to good yields.

Background: Licorice is widely used as a hepatoprotective herb for thousands of years in Traditional Chinese Medicine, and its main chemical constituent glycyrrhizin (GL) is used as a treatment for chronic hepatitis in Japan for over 20 years. 18β-Glycyrrhetinic acid (GA) is the main active metabolite of GL. Objective: Series of GA derivatives were designed and synthesized, and their anti-HCV activities were screened to investigate structure-activity relationship (SAR). Besides, their in-silico ADMET properties were analyzed to search for promising lead compound for further identification of anti-HCV terpenoid candidate. Methods: GA derivatives were synthesized via reactions of oxidation, oxime, rearrangement, esterification and acylation, etc. In vitro anti-HCV activity of derivatives was tested on the HCV cell culture (HCVcc) system. In-silico ADMET properties analysis were performed via “pkCSM” and “SwissADME” platforms. Results: Eighteen GA derivatives were synthesized and their structures were confirmed by MS and NMR spectrums. All compounds exhibited superior HCV inhibitory activity to that of GA. Compound 2 possessed the most potent anti-HCV activity with IC50 value of 0.79 μM, which is nearly 58 times potent than SA (a previously reported potent anti-HCV terpenoids) and >200 times than GA. SAR revealed the introduction of 3-oxo, short-chain (C1-C3) aliphatic alcohols or cyclic aliphatic amines is conducive to improving anti-HCV activity. In-silico ADMET prediction demonstrated most of the potent compounds possessed favorable ADMET properties. Conclusion: Structural modification of GA at 3-position and 30-position is an effective approach to searching for potent anti-HCV agents. Compound 2, with the most potent anti-HCV activity and favorable in-silico ADMET properties, is a promising lead compound for further identification of anti-HCV terpenoid candidate.

2-O-α- d- Glucopyranosyl-6-O-(2-propylpentanoyl)- l -ascorbic acid (6-bOcta-AA-2G) has shown a remarkable antitumor effect in an in vivo study. However, an efficient and low-cost process for synthesis of 6-bOcta-AA-2G has not been established yet. The process used for synthesis of 6-bOcta-AA-2G in this study consisted of three steps. The first step was acylation of l -ascorbic acid (AA) at the C-6 position with 2-propylpentanoic acid in concentrated H2SO4 at room temperature for 24 h to obtain 6-O-(2-propylpentanoyl)- l -ascorbic acid (6-bOcta-AA). Next, specific glycosylation of 6-bOcta-AA at the C-2 position by cyclodextrin glucanotransferase (CGTase) from Thermoanaerobacter sp. was carried out using soluble starch as a low-cost glycosyl donor in acetate buffer (pH 6.0) at 40 °C for 24 h. In this glycosylation reaction by CGTase, oligoglucosylated 6-bOcta-AAs seemed to be generated, and thus these oligoglucosides were further hydrolyzed by amyloglucosidase from Rhizopus sp. at 40 °C for 1 h in the reaction mixture containing CGTase to efficiently obtain 6-bOcta-AA-2G. The overall yield of 6-bOcta-AA-2G was 19.4 %. The presented synthetic process can be used for mass production of 6-bOcta-AA-2G as an antitumor agent.

Protein S-acylation is a prevalent post-translational protein lipidation that is dynamically regulated by “writer” protein S-acyltransferases and “eraser” acylprotein thioesterases. The protein S-acyltransferases are comprised of 23 Aspartate-Histidine-Histidine-Cysteine-containing (DHHC) proteins, which transfer fatty acid acyl groups from acyl-Coenzyme A (acyl-CoA) onto protein substrates. DHHC proteins are increasingly recognized as critical regulators of S-acylation-mediated cellular processes and pathology. As our understanding of the importance and breadth of DHHC-mediated biology and pathology expands, so too does the need for chemical inhibitors of this class of proteins. In this review, we discuss the challenges and progress in DHHC inhibitor development, focusing on 2-bromopalmitate (2BP), the most commonly used inhibitor in the field, and N-cyanomethyl-N-myracrylamide (CMA), a new broad-spectrum DHHC inhibitor. We believe that current and ongoing advances in structure elucidation, mechanismal interrogation, and novel inhibitor design around DHHC proteins will spark innovative strategies to modulate these critical proteins in living systems.

Relative rates for the Lewis base-catalyzed acylation of aryl-substituted 1,2-diols with anhydrides differing in size have been determined by turnover-limited competition experiments and absolute kinetics measurements. Depending on the structure of the anhydride reagent, the secondary hydroxyl group of the 1,2-diol reacts faster than the primary one. This preference towards the secondary hydroxyl group is boosted in the second acylation step from the monoesters to the diester through size and additional steric effects. In absolute terms the first acylation step is found to be up to 35 times faster than the second one for the primary alcohols due to neighboring group effects.

Poplar (Populus) lignin is naturally acylated with p-hydroxybenzoate ester moieties. However, the enzyme(s) involved in the biosynthesis of the monolignol–p-hydroxybenzoates have remained largely unknown. Here, we performed an in vitro screen of the Populus trichocarpa BAHD acyltransferase superfamily (116 genes) using a wheatgerm cell-free translation system and found five enzymes capable of producing monolignol–p-hydroxybenzoates. We then compared the transcript abundance of the five corresponding genes with p-hydroxybenzoate concentrations using naturally occurring unrelated genotypes of P. trichocarpa and revealed a positive correlation between the expression of p-hydroxybenzoyl-CoA monolig-nol transferase (pHBMT1, Potri.001G448000) and p-hydroxybenzoate levels. To test whether pHBMT1 is responsible for the biosynthesis of monolignol–p-hydroxybenzoates, we overexpressed pHBMT1 in hybrid poplar (Populus alba × P. grandidentata) (35S::pHBMT1 and C4H::pHBMT1). Using three complementary analytical methods, we showed that there was an increase in soluble monolignol–p-hydroxybenzoates and cell-wall-bound monolignol–p-hydroxybenzoates in the poplar transgenics. As these pendent groups are ester-linked, saponification releases p-hydroxybenzoate, a precursor to parabens that are used in pharmaceuticals and cosmetics. This identified gene could therefore be used to engineer lignocellulosic biomass with increased value for emerging biorefinery strategies.

The dehydroacylation of ketones to olefins is realized under mild conditions, which exhibits a unique reaction pathway involving aromatization-driven C–C cleavage to remove the acyl moiety, followed by Cu-mediated oxidative elimination to form an alkene between the α and β carbons. The newly-adopted N’-methylpicolinohydrazonamide (MPHA) reagent is key to enable efficient cleavage of ketone C–C bonds at room temperature. Diverse alkyl- and aryl-substituted olefins, dienes, and special alkenes are generated with broad functional group tolerance. Strategic applications of this method are also demonstrated.

A highly chemoselective cascade Wolff rearrangement/acylation reaction between 5-aminopyrazoles and diazo compounds has been developed. The protocol can facilitate the switchable synthesis of 4-hydroxy-pyrazolo[3,4-b]pyridin-6-ones and N-pyrazole amides with the merits of a broad substrate scope, high functional group compatibility, and green and sustainable performance manner. All reactions proceeded efficiently without any catalyst and additives (acid and base) and resulted in the release of benign N2, wherein diethyl carbonate served as a green benign solvent.

The borane FmesBH2 reacts in a three-component reaction with an isonitrile and a small series of organonitriles to give rare examples of the class of dihydro-1,4,2-diazaborole derivatives. In a related way, annulated BN-indolizine derivatives became conveniently available, as were dihydro-1,4,2-oxaza- or thiazaborole derivatives. The nucleophilic framework of a dihydro-1,4,2-diazaborole example allowed for an uncatalyzed acylation reaction. It also served as a 1,3-dipolar reagent and underwent a [3+2] cycloaddition/[4+2] cycloreversion sequence when treated with methyl propiolate to give the respective pyrrole product. The [3+2] cycloaddition product of a dihydro-1,4,2-diazaborole derivative with N-phenylmaleimide was isolated and its heterobicyclo[2.2.1]heptane derived structure characterized by X-ray diffraction.

5-Acetylcoumaran is an important pharmaceutical intermediate of darifenacin, and it is usually obtained through the acylation reaction of 2,3-dihydrobenzofuran catalyzed by anhydrous aluminum chlor...

A new [PCCP]-coordinated molybdenum platform comprising a coordinated alkyne was employed for the cleavage of molecular dinitrogen. The coordinated η2 -alkyne was left unaffected during this reduction. DFT calculations suggest that the reaction proceeds via an initially generated terminal N2 -complex, which is converted to a dinuclear μ-(η1 :η1 )-N2 -bridged intermediate prior to N-N bond cleavage. Protonation, alkylation and acylation of the resulting molybdenum nitrido complex led to the corresponding N-functionalized imido complexes. Upon oxidation of the N-acylated imido derivative in MeCN, a fumaronitrile fragment was built up via C-C coupling of MeCN to afford a dinuclear molybdenum complex. The key finding that the strong N≡N bond may be cleaved in the presence of a weaker, but spatially constrained C≡C bond contradicts the widespread paradigm that coordinated alkynes are in general more reactive than gaseous N2 .

Lipopolysaccharides (LPS) are cell wall components from Gram-negative bacteria and are composed of three covalently linked regions: the O-antigen, the core oligosaccharide, and the lipid A moiety, which carries most of their endotoxic activity. The objective of this study was to isolate and compare the lipid A structures from ruminal LPS derived from total mixed ration (TMR)- and pasture-fed cows, by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Ruminal bacteria were collected from two rumen-cannulated Holstein cows; one fed a TMR (60:40, forage–concentrate) and the other pasture fed. The representativeness of each sample was validated by comparing the rumen microbiome from the cows in our study to the core rumen microbiome from the previous literature. Lipopolysaccharides from each respective sample were extracted with a phenol–water extraction procedure and purified via ultracentrifugation. To isolate lipid A from the core and O-antigen, pure ruminal LPS samples were hydrolyzed with acetic acid. Lipid A derived from the TMR-fed cow potentially exhibited a tetra-acylated structure, whereas lipid A derived from the pasture-fed cow potentially exhibited a penta-acylated lipid A structure. Both samples were quantified using limulus amebocyte lysate (LAL) assay and exhibited low endotoxic activity, consistent with the MALDI-TOF MS observations. Results indicate that the lipid A acylation pattern differs between diets, and that ruminal bacteria express solely under-acylated lipid A structures contrary to hexa-acylated lipid A, typically expressed by bacteria such as E. coli.

Compared with the well-developed C–C and C–N axial chirality, the asymmetric synthesis of N–N axial chirality remains elusive and challenging. Herein we report the first atroposelective N-acylation reaction of quinazolinone type benzamides with cinnamic anhydrides for the direct catalytic synthesis of optically active atropisomeric quinazolinone derivatives. This reaction features mild conditions and a broad substrate scope and produces N–N axially chiral compounds with high yields and very good enantioselectivities. Besides, the synthetic utility of the protocol was proved by a large scale reaction, transformation of the product and the utilization of the product as an acylation kinetic resolution reagent. Moreover, DFT calculations provide convincing evidence for the interpretation of stereoselection., A highly efficient atroposelective N-acylation reaction of quinazolinone type benzamides with cinnamic anhydrides for the direct catalytic synthesis of optically active atropisomeric quinazolinone derivatives was developed.

Proanthocyanin (PA) dimers isolated from Acacia mearnsii bark were enzymatically acylated with palmitic acid as the acyl donor by immobilized Candida antarctica lipase on acrylic resin (Novozym 435). The acylation reaction conditions were optimized by comparing the amount of enzyme, the temperature, the reaction solvents, initial water content, substrate molar ratios and reaction time. The highest acylation conversion of 96.53% was achieved under the follow conditions: PA dimers/palmitic acid at a molar ratio of 1: 10 in tert-amyl alcohol; initial water content of 5% at 60 ℃ for 12 h with 30 g/L enzyme dosage. Introducing palmitic acid into PA dimers significantly improved both the lipophilicity and antioxidant properties. The 1-octanol/water partition coefficient of the PA dimers and their derivatives showed that the lipophilicity of the derivatives were 2.4 times higher than that of the PA dimers. The derivatives exhibited strong antioxidant scavenging capacities, approximately 1.6 times greater than the original dimers. This work is of great significance to expand the application of natural PA dimers in cosmetic and food industries and also lay a foundation for the high value-added utilization of A. mearnsii.

Considering the variation of the diffusion character of the three anhydrides, ultrasonication was applied for investigating its impact on the reaction efficiency of the rice starch acylation from three short-chain fatty acids (SCFAs). The current data indicated that the signal peak of the FTIR spectrum at 1720 cm−1 and additional resonances in the NMR confirmed the occurrence of the acylation reaction onto the starch molecules. More interestingly, this is the first study to reveal that a lower power density ultrasonication improved the reaction efficiencies of acetylation (19%), while a higher power density could lead to a reduced acylation reactivity of propionylation compared to the control one. On the contrary, the reaction efficiency of butyrylation (64%) was significantly enhanced by the ultrasound-assisted treatment with a greater association between reaction efficiency and ultrasonic power density, indicating the importance of the diffusion character for impacting the acylation reactivity among these three anhydrides. The ultrasonic-assisted SCFAs-modified rice starch has a lower peak viscosity and setback value, indicating that the replacement of the acyl groups for OH groups in the starch avoids starch molecules rearrangement. Meanwhile, the rheological properties exhibited that the starch achieved from ultrasonic-assistance significantly reduced the area of the hysteresis curve, suggesting a destroyed gel textural property. Thus, an appropriate ultrasonication but not all could effectively enhance the acylation efficiency and improve starch rheological property.

This study revealed that mixed chitin esters with long fatty and bulky acyl substituents were efficiently synthesized by acylation using acyl chlorides in the presence of pyridine and N,N-dimethyl-4-aminopyridine in an ionic liquid, 1-allyl-3-methylimidazolium bromide (AMIMBr), at 100 °C for 24 h. A stearoyl group was selected as the first substituent, which was combined with different long fatty and bulky acyl groups as the second substituents. In addition to IR analysis of the products, which suggested progress of the acylation, 1H NMR measurement was allowed for structural confirmation for high degrees of substitution (DSs) of the desired derivatives in CDCl3/CF3CO2H solvents. Crystalline structures and thermal property of the products were evaluated by powder X-ray diffraction and differential scanning calorimetry measurements, respectively. All the products showed film formability by casting from solutions in chloroform or chloroform/trifluoroacetic acid solvents. The occurrence of halogen exchange between acyl chlorides and AMIMBr in the present system was speculated to produce highly reactive acyl bromides in situ, which efficiently reacted with hydroxy groups in chitin to obtain high DS products.

The photo-/electrocatalytic functionalization of quinoxalin-2(1H)-ones has emerged as a promising and powerful approach for post-synthetic modification of quinoxalin-2(1H)-ones. This review provides an overview of recent developments in photo-/electrocatalytic functionalization of quinoxalin-2(1H)-ones including arylation, alkylation, fluoroalkylation, amination, phosphorylation, acylation, alkoxylation, thiolation, silylation, and annulation. The reaction scope and the related mechanism are also well discussed.

Gas chromatography–mass spectrometry (GC-MS) is useful for the quantitative determination of the polyamines spermidine (SPD) and putrescine (PUT) and of the biogenic amine agmatine (AGM) in biological samples after derivatization. This GC-MS method involves a two-step extraction with n-butanol and hydrochloric acid, derivatization with pentafluoropropionic anhydride (PFPA) in ethyl acetate, and extraction of the pentafluoropropionic (PFP) derivatives by toluene of SPD, PUT, and AGM. We wanted to extend this GC-MS method for the biogenic amine histamine (HA), but we faced serious problems that did not allow reliable quantitative analysis of HA. In the present work, we addressed this issue and investigated the derivatization of HA and the effects of toluene and ethyl acetate, two commonly used water-insoluble organic solvents in GC-MS, and oven temperature program. Derivatization of unlabelled HA (d0-HA) and deuterium-labelled HA (d4-HA) with PFPA in ethyl acetate (PFPA-EA, 1:4, v/v; 30 min, 65 °C) resulted in the formation of d0-HA-(PFP)2 and d4-HA-(PFP)2 derivatives. d4-HA and 13C4-SPD were used as internal standards for the amines after standardization. Considerable quantitative effects of toluene and ethyl acetate were observed. The starting GC column temperature was also found to influence considerably the GC-MS analysis of HA. Our study shows the simultaneous quantitative analysis of HA as HA-(PFP)2, AGM as AGM-(PFP)3, PUT as PUT-(PFP)2, and SPD as SPD-(PFP)3 derivatives requires the use of ethyl acetate for their extraction and injection into the GC-MS apparatus and a starting GC column temperature of 40 °C instead of 70 °C. The PFP derivatives of HA, AGM, PUT, and SPD were found to be stable in ethyl acetate for several hours at room temperature. Analytically satisfactory linearity, precision, and accuracy were observed for HA, AGM, PUT, and SPD in biologically relevant ranges (0 to 700 pmol). The limits of detection of AGM, PUT, and SPD were about two times lower in ethyl acetate compared to toluene (range, 1–22 fmol). The limits of detection were 1670 fmol for d0-HA and 557 fmol for d4-HA. Despite the improvements achieved in the study for HA, its analysis by GC-MS as a PFP derivative is challenging and less efficient than that of PUT, AGM, and SPD.

Immune sensing of the Gram-negative bacterial membrane glycolipid lipopolysaccharide (LPS) is both a critical component of host defense against Gram-negative bacterial infection, and a contributor to hyper-inflammatory response, leading to sepsis and death. Innate immune activation by LPS is due to the lipid A moiety, an acylated di-glucosamine molecule that can activate inflammatory responses via the extracellular sensor TLR4/MD2 or the cytosolic sensor caspase-11 (Casp11). The number and length of acyl chains present on bacterial lipid A structures vary across bacterial species and strains, which affects the magnitude of TLR4 and Casp11 activation. TLR4 and Casp11 are thought to respond similarly to various lipid A structures, as tetra-acylated lipid A structures do not activate either sensor, whereas hexa-acylated structures activate both sensors. However, direct analysis of extracellular and cytosolic responses to the same sources and preparations of LPS/lipid A structures have been limited, and the precise features of lipid A that determine the differential activation of each receptor remain poorly defined. To address this question, we used rationally engineered lipid A isolated from a series of bacterial acyl-transferase mutants that produce novel, structurally defined molecules. Intriguingly, we find that the location of specific secondary acyl chains on lipid A resulted in differential recognition by TLR4- or Casp11, providing new insight into the structural features of lipid A required to activate either TLR4- or Casp11. Our findings indicate that TLR4 and Casp11 sense non-overlapping areas of lipid A chemical space, thereby constraining the ability of Gram-negative pathogens to evade innate immunity.

Detection of Gram-negative bacterial lipid A by the extracellular sensor, myeloid differentiation 2 (MD2)/Toll-like receptor 4 (TLR4), or the intracellular inflammasome sensors, CASP4 and CASP5, induces robust inflammatory responses. The chemical structure of lipid A, specifically its phosphorylation and acylation state, varies across and within bacterial species, potentially allowing pathogens to evade or suppress host immunity. Currently, it is not clear how distinct alterations in the phosphorylation or acylation state of lipid A affect both human TLR4 and CASP4/5 activation. Using a panel of engineered lipooligosaccharides (LOS) derived from Yersinia pestis with defined lipid A structures that vary in their acylation or phosphorylation state, we identified that differences in phosphorylation state did not affect TLR4 or CASP4/5 activation. However, the acylation state differentially impacted TLR4 and CASP4/5 activation. Specifically, all tetra-, penta-, and hexa-acylated LOS variants examined activated CASP4/5-dependent responses, whereas TLR4 responded to penta- and hexa-acylated LOS but did not respond to tetra-acylated LOS or penta-acylated LOS lacking the secondary acyl chain at the 3′ position. As expected, lipid A alone was sufficient for TLR4 activation. In contrast, both core oligosaccharide and lipid A were required for robust CASP4/5 inflammasome activation in human macrophages, whereas core oligosaccharide was not required to activate mouse macrophages expressing CASP4. Our findings show that human TLR4 and CASP4/5 detect both shared and nonoverlapping LOS/lipid A structures, which enables the innate immune system to recognize a wider range of bacterial LOS/lipid A and would thereby be expected to constrain the ability of pathogens to evade innate immune detection.

Die vorliegende Arbeit konzentrierte sich auf die Entwicklung einer alternativen photochemischen Hydroacylierungsstrategie für elektronenarme Alkene. Unter Verwendung von 4-Acyl-Hantzsch-Estern als Radikalreservoir wurde ein effizientes Hydroacylierungsprotokoll entwickelt, das weder einen Photokatalysator noch irgendwelche Additive für den effizienten Acyltransfer benötigt. Nach Optimierung der Reaktionsbedingungen wurde ein Substratspektrum basierend auf Benzylidenmalonitril-Derivaten und Enonen etabliert. Die 4-Acylgruppe an Acyl-Hantzsch-Estern wurde ebenfalls variiert, um den elektronischen und sterischen Einfluss von Seiten der Reagenzien weiter zu untersuchen. Dieser Hydroacylierungsansatz ermöglichte auch Eintopfderivatisierungen, die einen direkten Zugang zu einer Reihe von formalen Alkenylierungsprodukten boten.Detaillierte mechanistische Studien wurden durchgeführt, um den Reaktionsmechanismus aufzuklären. Dabei zeigte sich, dass die Reaktion nicht über einen radikalischen Kettenmechanismus abläuft, dass sie durch die direkte Photoanregung der Hantzsch-Ester-Spezies bei 460 nm initiiert wird, und dass das so erzeugte Acylradikal mit dem aktivierten Alken-Substrat auf Giese-ähnliche Weise reagiert., This work focused on an alternative photochemical hydroacylation strategy for electron-poor alkenes. Using 4-acyl Hantzsch esters as radical reservoirs, an efficient hydroacylation protocol has been developed, which requires neither a photocatalyst nor any kind of additives for efficient acyl transfer. After optimisation of reaction conditions, a substrate scope based on benzylidenemalononitrile derivatives and enones was established. The 4-acyl group on acyl-Hantzsch esters was also varied to further investigate electronic and steric influence from the reagent side. This hydroacylation approach also enabled one-pot derivatisations, providing straightforward access to a set of formal alkenylation products.Detailed mechanistic studies were conducted to elucidate the reaction mechanism. This revealed, that the reaction proceeds via a non-chain radical mechanism, initiated by the direct photoexcitation of the Hantzsch ester species at 460 nm, and the generated acyl radical reacts with the activated alkene substrate in a Giese-like manner.

We report the use of

We developed a versatile asymmetric strategy to synthesize different classes of sulfoglycolipids (SGLs) from Mycobacterium tuberculosis. The strategy features the use of asymmetrically protected trehaloses, which were acquired from the glycosylation of TMS α-glucosyl acceptors with benzylidene-protected thioglucosyl donors. The positions of the protecting groups at the donors and acceptors can be fine-tuned to obtain different protecting-group patterns, which is crucial for regioselective acylation and sulfation. In addition, a chemoenzymatic strategy was established to prepare the polymethylated fatty acid building blocks. The strategy employs inexpensive lipase as a desymmetrization agent in the preparation of the starting substrate and readily available chiral oxazolidinone as a chirality-controlling agent in the construction of the polymethylated fatty acids. A subsequent investigation on the immunomodulatory properties of each class of SGLs showed how the structures of SGLs impact the host innate immunity response.

An efficient, high-yielding and scalable procedure for the regioselective 3-acylation of indoles with anhydrides promoted by boron trifluoride etherate under mild conditions was reported. This novel protocol provided a simple way to prepare 3-(benzofuran-2-yl) indole in three steps.

Design of ligands in transition-metal catalyzed reactions is challenging, especially in asymmetric transformations. With each step in the catalytic cycle promoted by its privileged ligand and different steps well-connected by dynamic ligand exchange, synergistic combination of multiple ligands could potentially enhance the catalytic efficiency and selectivity. Now, this concept has been applied to the NiH-catalyzed asymmetric remote hydroacylation of olefins and migratory acylation of alkyl halides with excellent regio- and enantioselectivity, utilizing two simple ligands, one for chain-walking and the other for asymmetric acylation. Starting from abundant alkenes/alkyl halides and carboxylic acids, a wide range of enantioenriched chiral α-aryl ketones can be efficiently accessed under mild conditions.

Pseudaminic acid and its biosynthetic altropyranoside precursors are bacterial components currently being investigated toward novel antibacterial strategies. One structural feature associated with these naturally occurring flagellar carbohydrates is the different

Dynamic kinetic resolution allows for the synthesis of enantiomerically pure asymmetric alcohols. Cyclopentadienyl-derived ruthenium catalysts were immobilized with an ionic liquid, [BMIM][NTf2], on multiwall carbon nanotubes and used for the racemization of chiral secondary alcohols. This successful approach was combined with the enantioselective enzymatic acylation of secondary alcohols (1-phenylethanol and 1-(1-naphthyl)ethanol) using Novozyme® 435. The resulting catalytic system of the ruthenium racemization catalysts and enzymatic acylation led to chiral esters being obtained by dynamic kinetic resolution. The immobilized catalytic system in the ionic liquid gave the same activity of >96% yield within 6 h and a selectivity of 99% enantiomeric excess as the homogeneous system, while allowing for the convenient separation of the desired products from the catalyst. Additionally, the process can be regarded as green, since the efficient reuse of the catalytic system was demonstrated.