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Comprehensive Summary: Chiral phosphine‐catalyzed asymmetric (4+2) annulation of the amide‐based Morita–Baylis–Hillman (MBH) carbonates with β,γ‐unsaturated butenolides has been developed to give enantiomer‐enriched bicyclic δ‐lactam γ‐butyrolactone compounds. The amide‐based MBH carbonates were first used as acceptor and aza‐C4 synthon in phosphine catalysis. Under mild reaction conditions, a variety of amide‐based MBH carbonates and unsaturated butenolides were well tolerated to provide chiral bicyclic δ‐lactam γ‐butyrolactone derivatives in high yields with excellent enantioselectivities as well as diastereoselectivities. A plausible reaction mechanism was also proposed based on control experiments and DFT calculations. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Chiral phosphine‐catalyzed asymmetric (4+2) annulation of the amide‐based Morita–Baylis–Hillman (MBH) carbonates with β,γ‐unsaturated butenolides has been developed to give enantiomer‐enriched bicyclic δ‐lactam γ‐butyrolactone compounds. The amide‐based MBH carbonates were first used as acceptor and aza‐C4 synthon in phosphine catalysis. Under mild reaction conditions, a variety of amide‐based MBH carbonates and unsaturated butenolides were well tolerated to provide chiral bicyclic δ‐lactam γ‐butyrolactone derivatives in high yields with excellent enantioselectivities as well as diastereoselectivities. A plausible reaction mechanism was also proposed based on control experiments and DFT calculations. [ABSTRACT FROM AUTHOR]

Abstract Polyether sulfone sulfamic acid (PES-NHSO3H) was prepared by simple sulfonation of a modified polyether sulfone. The number of acidic sites (SO3H) was determined to be 4.23 mmol H+/g by acid-base titration and 4.29 mmol H+/g by barium sulfate test. PES-NHSO3H was used as an efficient acidic catalytic system for the preparation of functionalized furan-2-ones and 2ʹ,5-dioxo-5 H-spiro[furan-2,3 ʹ -indoline]-3-carboxylate derivatives via the three-component reaction of anilines, aldehydes/1-ethylindoline-2,3-dione, and diethyl acetylene dicarboxylate in high yields (85–97%). The effect of polar and non-polar solvents on the productivity of the reaction was investigated. The catalyst was recovered 11 times without losses in catalytic potential.

In the quest for sustainable paints and coatings, bio-based resources for the polymeric binder constituents are key. Recently, we introduced poly-butenolides as bio-based acrylate replacement for solventborne and 100% solids (UV-curing) coatings. Here, we report the first step towards aqueous poly-butenolide dispersions, enabling the use of this novel binder technology platform in waterborne coatings. [ABSTRACT FROM AUTHOR]

Objectives: The genus Glochidion (the family Phyllanthaceae) is used for various medicinal purposes, such as dysentery, diarrhea, cough, and skin protection. A review of phytochemical and pharmacological aspects for this remains unavailable. The current study tends to sum up a detailed list of phytochemicals, and their role in biological examinations. Methods: References in English were obtained by an extensive search across various electronic data sources, encompassing Web of Science, PubMed, Google Scholar, and Science Direct. The "Sci-Finder" was also utilized to find references and revise chemical structures. Referenced documents have been gathered from the 1960s to date. It also noted that Glochidion, phytochemistry, and pharmacology are likely the keywords to seek for references. Results: Over 240 naturally occurring phytochemicals were isolated and identified from various Glochidion tissues, including terpenoids, sterols, saponins, lignans, flavonoids, mono -phenols, megastigmanes, butenolides, glycosides, alkaloids, cyanogens, tocopherols, fatty acids, and others. Three naturally occurring triterpenoids glochidonol, glochidiol, and glochidone are the likely characteristic metabolites, being isolated frequently. Glochidion crude extracts and their isolated compounds have been demonstrated as potential agents in various pharmacological targets, such as cytotoxicity, antioxidant, antiinflammation, and neuron and liver protection. Conclusion: Several isolates acted as promising agents in pharmacological assays. The anticancer mechanisms of various triterpenoids and saponins, especially new and potential compounds, are expected. Pharmacological advancements to enhance the efficacies of Glochidion constituents, such as synergistic combinations and nano-drug formulations, are encouraged. [ABSTRACT FROM AUTHOR]

Two previously described Brønsted acidic ionic liquids, 3,3′-(1,6-hexanediyl)bis(1-methyl)-1H-imidazolium hydrogen sulfate (Cat1) and 1,1′-(1,6-hexanediyl)bis(pyridinium) hydrogen sulfate (Cat2), were used as catalysts for the preparation of spiro[furan-2,3′-indoline]-3-carboxylate derivatives via a three-component reaction of anilines, isatins (N-alkyl-indoline-2,3-diones), and diethyl acetylenedicarboxylate, in high yields. The use of ultrasonic (US) irradiation led to the targeted products (1a–15a) in high yields ranging from 80% to 98%. Under the same conditions, the use of sulfuric acid and acetic acid as a Brønstedt catalyst did not yield the desired benchmark product 1a. [ABSTRACT FROM AUTHOR]

This article discusses a study on the development of a new catalyst for the asymmetric isomerization of β,γ-unsaturated butenolides. The researchers found that chiral betaines derived from precursors were highly efficient catalysts for this reaction. They optimized the reaction conditions and successfully synthesized a range of chiral α,β-butenolides with high enantioselectivity. This research has potential applications in the synthesis of biologically active molecules. The study provides a detailed description of the catalytic cycle and suggests that chiral betaines could be used in various catalytic asymmetric reactions. The supporting information for the study is available online. [Extracted from the article]

This article discusses the synthesis of hybrid molecules that contain both γ-butyrolactone and γ-butyrolactam motifs, which are important in pharmaceutical science. The authors developed a method for regioselective difunctionalization of deconjugated butyrolactones using α-amide enones as Michael acceptors, resulting in high yields and excellent diastereoselectivity. The study provides a simple and efficient approach to the synthesis of these hybrid molecules. Additionally, the article briefly mentions the celebration of Yamamoto's 80th birthday, but does not provide any further details about the event or Yamamoto himself. [Extracted from the article]

Alkyne‐carbonyl metathesis is a type of carbon‐carbon forming reaction involving the construction a carbon‐carbon double bond and a carbonyl group in one transformation. Herein, a Au(I)‐catalyzed ring‐closing alkyne‐carbonyl metathesis protocol has been developed to make densely substituted γ‐butenolides from propargyl α‐ketoesters. It features 100 % atom economy, excellent substrate flexibility and benign functional group tolerance. Mechanistic studies demonstrate that the coordinative interaction between the gold catalyst and the alkyne might initiate the transfer of an oxygen atom and the formation of the carbon‐carbon double bond. By using this gold‐catalyzed ring‐closing alkyne‐carbonyl metathesis as a key step reaction, four naturally occurring butenolide‐type compounds including decumbic acid (45 % yield for 3 steps), deoxyisosporothric acid (32 % yield for 5 steps), lichesterinic acid (34 % yield for 5 steps) and isomuronic acid (6 % yield for 8 steps) have been synthesized starting from commercially available starting materials. [ABSTRACT FROM AUTHOR]

Urease is an important virulence factor involved in the colonization and infection of gastric mucosa by Helicobacter pylori. In this work, the urease inhibitory activity of a series of γ-alkylidenebutenolides analogues of natural rubrolides is presented. The compounds were prepared from a commercial 3,4-dibromofuran-(5H)-2-one, as previously reported, including three new derivatives. The rubrolide analogues (at 500 µM) showed percentages of urease inhibition ranging from 20.7 to 99.3%. The most active compounds (IC50 from 111.5 to 306.0 µM) were shown to be more potent than hydroxyurea (IC50 844.4 µM), a standard urease inhibitor. Rubrolide analogues with phenolic hydroxyl groups revealed higher potency compared with other substances evaluated. Their physicochemical parameters (partition coefficient, molecular weight, hydrogen bonding acceptors, number of hydrogen bonding donor groups, number of rotatable bonds, and the number of aromatic bonds) related to general pharmacokinetic requirements showed drug-like properties for the evaluated rubrolide analogues. Docking studies suggest that the presence of hydroxy groups at the ortho position favors both the formation of reversible interactions with urease and the formation of a covalent adduct with the active site causing blocking of the enzyme, like what happens with catechol, its natural inhibitor. The high biological activity herein reported indicates that rubrolides constitute promising leads for the development of a new class of urease inhibitor drugs. [ABSTRACT FROM AUTHOR]

The current nanomedicinal approach combines medicinal plants and nanotechnology to create new scaffolds with enhanced bioavailability, biodistribution and controlled release. In an innovative approach to herb encapsulation in nanosized chitosan matrices, wild-grown Romanian Helleborus purpurascens was used to prepare two new chitosan nanocarriers. The first carrier preparation involved the nanoencapsulation of hellebore in chitosan. The second carrier emerged from two distinct stages: hellebore-AgNPs phyto-carrier system succeeded by nanoencapsulation in chitosan. The morphostructural characteristics and thermal behavior of these newly prepared nanocarriers were examined using FT-IR, XRD, DLS, SEM, EDS and thermogravimetric analyses. In addition, the encapsulation yield, encapsulation efficiency and encapsulation contents were investigated. The antioxidant activity was estimated using four in vitro, noncompetitive methods: total phenolic assay; 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay; phosphomolybdate (i.e., total antioxidant capacity); and iron(III)-phenanthroline antioxidant assay. Moreover, this study reports the first low-molecular-weight metabolite profile of wild-grown Romanian Helleborus purpurascens Waldst. & Kit. A total of one hundred and five secondary metabolites were identified in the mass spectra (MS)-positive mode from fourteen secondary metabolite categories (alkaloids, butenolides, bufadienolides, phytoecdysteroids, amino acids and peptides, terpenoids, fatty acids, flavonoids, phenolic acids, sterols, glycosides, carbohydrates, nucleosides and miscellaneous). The collective results suggest the potential application is a promising new antioxidant vehicle candidate in tumor therapeutic strategy. [ABSTRACT FROM AUTHOR]

Aim This study aimed to use one strain many compounds approach (OSMAC) to investigate the cytotoxic potential of Aspergillus terreus associated with soybean versus several cancer cell lines, by means of in-silico and in vitro approaches. Methods and results Fermentation of the isolated strain was done on five media. The derived extracts were investigated for their inhibitory activities against three human cancer cell lines; mammary gland breast cancer (MCF-7), colorectal adenocarcinoma (Caco-2), and hepatocellular carcinoma (HepG2) using MTT Assay. The fungal mycelia fermented in Modified Potato Dextrose Broth (MPDB) was the most cytotoxic extract against HepG2, MCF-7, and Caco-2 cell lines with IC50 4.2 ± 0.13, 5.9 ± 0.013 and 7.3 ± 0.004 μg mL−1, respectively. MPDB extract was scaled up resulting in the isolation of six metabolites; three fatty acids (1, 2, and 4), one sterol (3) and two butenolides (5 and 6) by column chromatography. The isolated compounds (1–6) were screened through a molecular docking approach for their binding aptitude to various active sites. butyrolactone-I (5) revealed a significant interaction within the CDK2 active site, while aspulvinone E (6) showed promising binding affinity to FLT3 and EGFR active sites that was confirmed by in vitro CDK2, FLT3 and EGFR inhibitory activity. Finally, the in vitro cytotoxic activities of butyrolactone-I (5) and aspulvinone E (6) revealed the antiproliferative activity of butyrolactone-I (5), against HepG2 cell line (IC50 = 17.85 ± 0.32 μM). Conclusion Molecular docking analysis and in vitro assays suggested the CDK2/A2 inhibitory potential of butyrolactone-I (5) in addition to the promising interaction abilities of aspulvinone E (6) with EGFR and FLT3 active sites as a possible mechanism of their biological activities. [ABSTRACT FROM AUTHOR]

Two new disubstituted maleimides, aspergteroids G–H (1–2), and two trisubstituted butenolides aspergteroids I–J (3–4), along with four known analogs, were isolated and structurally identified from the fermentation extract of soft-coral-associated symbiotic and epiphytic fungus Aspergillus terreus EGF7-0-1. The structures of the new compounds were established mainly via spectroscopic data analyses, and their absolute configurations were determined via X-ray diffraction analysis and comparison of the calculated and experimental electronic circular dichroism. Myocardial protection assays showed that compounds 1, 2, 5, and 6 possess protective effects against tert-butyl hydroperoxide (TBHP)-induced H9c2 (rat myocardial cells) apoptosis at low concentrations. Based on the analyses of the protein–protein interaction (PPI) network and Western blotting, compound 1 may inhibit the apoptosis and inflammatory response of cardiomyocytes after TBHP induction and improve the antioxidant capacity of cardiomyocytes. We speculate that the anti-inflammatory response of compound 1 is suppressed by the glycogen synthase kinase-3 beta (GSK-3β), downregulated by the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation, and suppressed by the expression of cysteinyl aspartate specific proteinase-3 (caspase-3) and B-cell lymphoma-2 associated X protein (Bax). [ABSTRACT FROM AUTHOR]

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Abstract Background Fungi biosynthesize a wide range of chemically diverse secondary metabolites during processes of competition with other micro- and macro-organisms, symbiosis, parasitism, or pathogenesis. Some of these natural compounds have antibiotic properties, which allow the microbe to inhibit and/or kill their microbial competitors. Results In the course of an ongoing search for novel bioactive metabolites from Trichoderma harzianum M10 using OSMAC (One Strain MAny Compounds) strategy, a bioactive chromone derivative has been isolated. The 5-hydroxy-2,3-dimethyl-7-methoxychromone (1), purified for the first time from T. harzianum M10 and induced in specific medium (potato dextrose broth, PDB) and condition (light and shaking), has been obtained as pure crystals and its structure has been fully characterized using X-ray and spectroscopic methods. This metabolite revealed a significant antibiotic activity against Rhizoctonia solani (45% of growth inhibition after 24 h of incubation at a concentration of 100 ng plug−1) and significantly reduced the viability of colorectal human cancer cells in a concentration-dependent manner. Moreover, metabolomic analysis allowed the identification of compounds modulated by the cultivating conditions. Among the statistically different molecules detected it was possible to identify siderophores, such as ferricrocin and coprogen B, harzianic acid (and its derivatives), and butenolides. Conclusion OSMAC strategy represents a valuable approach to overcome the limitations of experiments performed under laboratory conditions. Indeed, it is possible to modulate metabolites production by changing medium and conditions applied to the cultures. A specific set of conditions induced the production of a secondary metabolite never isolated from T. harzianum M10. The compound, a methoxychromone derivative, characterized by X-ray diffraction, mass spectrometry, IR, and NMR, displayed antimicrobial and antitumor activities. Graphical Abstract

This article describes a method for synthesizing butyrolactone dimers using various inorganic silver salt catalysts. The method was successfully applied to alkyl 2-(2-bromopropyl)malonate 1, providing the dimeric butyrolactone 2 when catalyzed by different silver salt catalysts. This synthesis method not only simplifies the original synthetic route, but also cleverly combines with natural product analogs, providing a strategy for the development of natural product polymer analogs in the future. [ABSTRACT FROM AUTHOR]

Two previously described Brønsted acidic ionic liquids, 3,3′-(1,6-hexanediyl)bis(1-methyl)-1H-imidazolium hydrogen sulfate (Cat1) and 1,1′-(1,6-hexanediyl)bis(pyridinium) hydrogen sulfate (Cat2), were used as catalysts for the preparation of spiro[furan-2,3′-indoline]-3-carboxylate derivatives via a three-component reaction of anilines, isatins (N-alkyl-indoline-2,3-diones), and diethyl acetylenedicarboxylate, in high yields. The use of ultrasonic (US) irradiation led to the targeted products (1a–15a) in high yields ranging from 80% to 98%. Under the same conditions, the use of sulfuric acid and acetic acid as a Brønstedt catalyst did not yield the desired benchmark product 1a.

Background: Fungi biosynthesize a wide range of chemically diverse secondary metabolites during processes of competition with other micro- and macro-organisms, symbiosis, parasitism, or pathogenesis. Some of these natural compounds have antibiotic properties, which allow the microbe to inhibit and/or kill their microbial competitors. Results: In the course of an ongoing search for novel bioactive metabolites from Trichoderma harzianum M10 using OSMAC (One Strain MAny Compounds) strategy, a bioactive chromone derivative has been isolated. The 5-hydroxy-2,3-dimethyl-7-methoxychromone (1), purified for the first time from T. harzianum M10 and induced in specific medium (potato dextrose broth, PDB) and condition (light and shaking), has been obtained as pure crystals and its structure has been fully characterized using X-ray and spectroscopic methods. This metabolite revealed a significant antibiotic activity against Rhizoctonia solani (45% of growth inhibition after 24 h of incubation at a concentration of 100 ng plug−1) and significantly reduced the viability of colorectal human cancer cells in a concentration-dependent manner. Moreover, metabolomic analysis allowed the identification of compounds modulated by the cultivating conditions. Among the statistically different molecules detected it was possible to identify siderophores, such as ferricrocin and coprogen B, harzianic acid (and its derivatives), and butenolides. Conclusion: OSMAC strategy represents a valuable approach to overcome the limitations of experiments performed under laboratory conditions. Indeed, it is possible to modulate metabolites production by changing medium and conditions applied to the cultures. A specific set of conditions induced the production of a secondary metabolite never isolated from T. harzianum M10. The compound, a methoxychromone derivative, characterized by X-ray diffraction, mass spectrometry, IR, and NMR, displayed antimicrobial and antitumor activities. [ABSTRACT FROM AUTHOR]

Herein, a novel switchable multipath cascade cyclization via chemodivergent reaction between readily available ketoamides and deconjugated butenolides was developed to efficiently synthesize γ-lactone fused γ-lactams and succinimide fused hemiketals. The Aldol/aza-Michael reaction and Aldol/imidation/hemiketalization reaction were enabled by catalytic amounts of two bases, namely tetramethyl guanidine and NaOAc. A wide range of substrate scope with diverse functional group compatibility was demonstrated to deliver the corresponding products with good yield and excellent diastereoselectivity (>60 examples). [ABSTRACT FROM AUTHOR]

In tumor cells, ketolysis "via" succinyl-CoA: 3-oxoacid-CoAtransferase (SCOT) and acetyl-CoA acetyltransferase 1 (ACAT1) is a major source of mitochondrial acetyl-CoA. Active ACAT1 tetramers stabilize by tyrosine phosphorylation, which facilitates the SCOT reaction and ketolysis. Tyrosine phosphorylation of pyruvate kinase PK M2 has the opposite effect, stabilizing inactive dimers, while pyruvate dehydrogenase (PDH), which is already inhibited by phosphorylation, is acetylated by ACAT1 and is doubly locked. This closes the glycolytic supply of acetyl-CoA. In addition, since tumor cells must synthesize fatty acids to create new membranes, they automatically turn off the degradation of fatty acids into acetyl-CoA ("via" the malonyl-CoA brake for the fatty acid carnityl transporter). Thus, inhibiting SCOT the specific ketolytic enzyme and ACAT1 should hold back tumor progression. However, tumor cells are still able to take up external acetate and convert it into acetyl-CoA in their cytosol "via" an acetyl-CoA synthetase, which feeds the lipogenic pathway; additionally, inhibiting this enzyme would make it difficult for tumor cells to form new lipid membrane and survive. [ABSTRACT FROM AUTHOR]

Totally substituted butenolide including two tetrasubstituted olefins is a distinct structural motif seen in Stemona alkaloids, but efficient methods for its synthesis are not well developed. As an ongoing program aimed at the collective total synthesis of the stemoamide group, we report a stereodivergent method to give either (E)- or (Z)-totally substituted butenolide from the same intermediate. While AgOTf--mediated elimination via an E1-type mechanism results in the formation of the kinetic (Z)-tetrasubstituted olefin, subsequent TfOH-mediated isomerization gives the thermodynamic (E)-tetrasubstituted olefin. The pyrrole ring is another important structure found in Stemona alkaloids. The direct oxidation of pyrrolidine rings with MnO2 and careful purification gives the pyrrole groups without isomerization of the stereocenter in the lactone group. These two methods enabled us to synthesize a series of stemoamide-type alkaloids including tricyclic, tetracyclic, and pentacyclic frameworks. The anti-inflammatory activities by inhibition of iNOS expression in macrophage cell line RAW264.7 indicate that the most potent anti-inflammatory compounds without cytotoxicity are protostemonines, which consist of pentacyclic frameworks including the totally substituted butenolide. [ABSTRACT FROM AUTHOR]

A new glyoxylate-containing benzene derivative, methyl 2-(4-hydroxy-3-(3′-methyl-2′-butenyl)phenyl)-2-oxoacetate (1), together with ten known compounds (2–11), were isolated from the marine algicolous fungus, Aspergillus sp. SCSIO 41304. Their planar structures and absolute configurations were elucidated by detailed NMR, MS spectroscopic analysis and comparing with literature data. Compound 1 was isolated as a new fungal secondary metabolite, possessing a methyl glyoxylate moiety R-CO-CO-OCH3, which is rare in natural sources. All the isolated compounds (1–11) were tested for their antibacterial and enzyme inhibitory activities against acetylcholinesterase (AChE) and pancreatic lipase (PL). Among these compounds, aspulvinone H (4) showed moderate inhibition against AChE and PL with IC50 values of 25.95 and 47.06 μM, respectively. Further molecular docking simulation exhibited that compound 4 could well bind to the catalytic pockets of the AChE and PL. [ABSTRACT FROM AUTHOR]

The reaction of phenols or aryl ethers with tetronic acid mediated by BF3 ·OMe2 was investigated. This strategy allowed for the preparation of β-(hydroxyaryl)butenolides and β-arylbutenolides in a single step in a simpler way than previously reported synthetic methods [ABSTRACT FROM AUTHOR]

The reaction of phenols or aryl ethers with tetronic acid mediated by BF3 ·OMe2 was investigated. This strategy allowed for the preparation of β-(hydroxyaryl)butenolides and β-arylbutenolides in a single step in a simpler way than previously reported synthetic methods [ABSTRACT FROM AUTHOR]

The only known sulfur-containing karrikin, 3-methyl-2H-thiopyrano[3,4-b]furan-2-one, has been recently identified as an extremely efficient neuroprotective butenolide. Herein, we report the targeted synthesis of this compound as well as new synthetic protocols toward a class of compounds derived from 2H-furo[2,3-c]pyran-2-ones (karrikins) via bioisosteric exchange of oxygen with sulfur. In particular, we present synthetic procedures toward bioisosteres of karrikins with one or two sulfur heteroatoms incorporated into the core backbone together with evaluation of their biological activity in inhibition of acetylcholinesterase.

Butyrolactones are prevalent structural elements in many natural products. Vinylogous conjugate additions of butenolides are among the most promising synthetic methods for generating natural products and/or natural product‐like compounds with potential biological activities. In this report, direct 1,6‐conjugate addition of butenolide to p‐quinone methides via Brønsted base catalysis was performed, which provides an efficient route to interesting molecules. The reaction proceeds with a regioselective γ‐attack of butenolide and shows good functional group tolerance. [ABSTRACT FROM AUTHOR]

The effects of Piper malacophyllum (C. Pesl) C. DC extracts and its isolated compounds were analysed in a mouse model of primary dysmenorrhoea (PD). Female Swiss mice (6–8 weeks old) on proestrus were intraperitoneally treated with estradiol benzoate for 3 days, to induce PD. Twenty-four hours later, animals were treated 24 h later with vehicle, plant extract, gibbilimbol B, 4,6-dimethoxy-5-E-phenylbutenolide, mixture of 4,6-dimethoxy-5-E-phenylbutenolide and 4,6-dimethoxy-5-Z-phenylbutenolide, or ibuprofen. One hour later, oxytocin was injected and the numbers of abdominal writhing were counted. Then, mice were euthanized and uteri were collected for morphometrical and histological analyses. The effects of P. malacophyllum in inflammation were investigated in mouse peritoneal neutrophils culture stimulated with LPS or fMLP (chemotaxis and mediator release). Finally, uterus contractile and relaxing responses were assessed. Similar to ibuprofen, P. malacophyllum extract and isolated compounds reduced abdominal writhing in mice with PD. Histology indicated a marked neutrophil and mast cell infiltrate in the uterus of PD animals which was attenuated by the extract. The compounds and the extract reduced neutrophil chemotaxis and inflammatory mediator release by these cells. Reduced TNF levels were also observed in uteri of PD mice treated with P. malacophyllum. The extract did not affect spontaneous uterine contractions nor those induced by carbachol or KCl. However, it caused relaxation of oxytocin-induced uterine contraction, an effect blunted by H1 receptor antagonist. Overall the results indicate that P. malacophyllum may represent interesting natural tools for reliving PD symptoms, reducing the triad of pain, inflammation and spasmodic uterus behaviour. [ABSTRACT FROM AUTHOR]

In order to improve the antifungal activity of new butenolides containing oxime ether moiety, a series of new butenolide compounds containing methoxyacrylate scaffold were designed and synthesized, based on the previous reports. Their structures were characterized by 1H NMR, 13C NMR, HR-MS spectra, and X-ray diffraction analysis. The in vitro antifungal activities were evaluated by the mycelium growth rate method. The results showed that the inhibitory activities of these new compounds against Sclerotinia sclerotiorum were significantly improved, in comparison with that of the lead compound 3–8; the EC50 values of V-6 and VI-7 against S. sclerotiorum were 1.51 and 1.81 mg/L, nearly seven times that of 3–8 (EC50 10.62 mg/L). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observation indicated that compound VI-3 had a significant impact on the structure and function of the hyphal cell of S. sclerotiorum mycelium and the positive control trifloxystrobin. Molecular simulation docking results indicated that the introduction of methoxyacrylate scaffold is beneficial to improving the antifungal activity of these compounds against S. sclerotiorum, which can be used as the lead for further structure optimization. [ABSTRACT FROM AUTHOR]

A new series of butene lactone derivatives were designed according to an influenza neuraminidase target and their antiviral activities against H1N1 infection of Madin–Darby canine kidney cells were evaluated. Among them, a compound that was given the name M355 was identified as the most potent against H1N1 (EC50 = 14.7 μM) with low toxicity (CC50 = 538.13 μM). It also visibly reduced the virus‐induced cytopathic effect. Time‐of‐addition analysis indicated that H1N1 was mostly suppressed by M355 at the late stage of its infectious cycle. M355 inhibited neuraminidase in a dose‐dependent fashion to a similar extent as oseltamivir, which was also indicated by a computer modeling experiment. In a mouse model, lung lesions and virus load were reduced and the expression of nucleoprotein was moderated by M355. The enzyme‐linked immunosorbent assay and quantitative real‐time polymerase chain reaction analyses revealed that the levels of interferon‐γ, interferon regulatory factor‐3, Toll‐like receptor‐3, tumor necrosis factor‐α, interleukin (IL)‐1β, IL‐6, and IL‐8 were downregulated in the M355‐treated groups, whereas the levels of IL‐10 and IL‐13 were upregulated. Similarly, IgG was found to be increased in infected mice plasma. These results demonstrate that M355 inhibit the expression of H1N1 in both cellular and animal models. Thus, M355 has the potential to be effective in the treatment of influenza A virus infection. [ABSTRACT FROM AUTHOR]

Five undescribed γ-butyrolactones harzianolides B F (1 – 5), one precursor harzianolide G (6) along with two known analogues, were isolated and identified from the EtOAc extract of the liquid fermentation of Trichoderma harzianum ZN-4, which was obtained from the sediment of Zhoushan coastal area. Notably, compound 1 featured an unusual carbon skeleton with methylene-bridged furan rings system. Their structures were determined by detailed interpretation of NMR and mass spectroscopic data, and the absolute configurations were unambiguously established based on ECD quantum chemical calculations. In bioassay, 1 and 7 showed inhibitory activity against Pestalotiopsis theae , with MIC values of 25 and 50 μg/mL, respectively. [Display omitted] • Five undescribed butenolide analogues and one precursor were isolated from Trichoderma harzianum. • Two compounds exhibited anti- Pestalotiopsis theae activity. • Compound 1 possesses an unusual methylene-bridged furan rings system. [ABSTRACT FROM AUTHOR]

γ‐Butenolide and γ‐butyrolactone scaffolds are two types of important core structures in numerous natural products and bioactive targets. However, methods to construct the chiral quaternary arylated γ‐butenolide are rarely explored. We herein report an efficient Pd‐catalyzed enantioselective γ‐arylation of β,γ‐unsaturated butenolides with aryl bromides, which shows high γ‐selectivity, good functional group tolerance and excellent enantioselectivity. Notably, this protocol also allows for facile construction of tricyclic tetrahydroindolines and tetrahydroisoquinolinones in one step. DFT calculations are consistent with the experimental results, suggesting that the γ‐arylation is favoured over the α‐arylation. Finally, this method is applied to the rapid synthesis of natural product (R)‐(+)‐boivinianin A. [ABSTRACT FROM AUTHOR]

Butenolides are a family of lactones containing a double bond and have been frequently found in the extracts of Streptomyces bacterial species with various pharmacological activities. In this study, seven butenolides (1–7) were discovered and isolated from the culture broth of a marine-derived Streptomyces sp. 13G036 based on a molecular networking analysis. Among the seven isolates, compound 7 was first isolated as a natural product in this study. The structures of compounds 1–7 were determined by combined analysis of 1D/2D Nuclear Magnetic Resonance (NMR) spectra, Mass Spectrometry (MS) spectra and electronic circular dichroism (ECD) data. Compounds 1–6 showed potential anti-inflammatory activities by inhibiting the production of nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukine-6 (IL-6) in lipopolysaccharide-stimulated macrophages. [ABSTRACT FROM AUTHOR]

Extensive metabolite analysis of Streptomyces rochei 7434AN4 was performed to discover uncharacterized secondary metabolites. A mutant strain of S. rochei , in which two regulatory genes srrC (a tetR-type repressor) and srrY (SARP-type activator) were inactivated, accumulated three 4-monosubstituted γ-butyrolactones YT02-A, YT02-B, and KH01-A, which were not detected in the parent strain. Their structures were identified as 4,10-dihydroxy-10-methyldodecan-4-olide, 4,10-dihydroxy-10-methylundecan-4-olide, and 4-hydroxy-11-oxo-10-methyldodecan-4-olide. A structural comparison indicated that the three butanolides and the signaling molecules, termed S. rochei butenolides (SRBs), could share common C 12 or C 13 fatty acids for their biosynthesis intermediates, however, these three butanolides did not induce antibiotic production even at 50 μM concentration (1000-folds of the minimum antibiotic-inducing concentration of SRBs) in S. rochei. [Display omitted] [ABSTRACT FROM AUTHOR]

Amid the current COVID‐19 pandemic, the emergence of several variants in a relatively high mutation rate (twice per month) strengthened the importance of finding out a chemical entity that can be potential for developing an effective medicine. In this study, we explored ethyl acetate (EtOAc) extract of a marine‐derived fungus Aspergillus cosatricaensis afforded three butenolide derivatives, butyrolactones I, VI and V (1–3), two naphtho‐γ‐pyrones, TMC‐256 A1 (4) and rubrofusarin B (5) and methyl p‐hydroxyphenyl acetate (6). Structure identification was unambiguously determined based on exhaustive spectral analyses including 1D/2D NMR and mass spectrometry. The isolated compounds (1–6) were assessed for their in vitro anti‐inflammatory, antiallergic, elastase inhibitory activities and in silico SARS‐CoV‐2 main protease (Mpro). Results exhibited that only butenolides (1 and 2) revealed potent activities similar to or more than reference drugs unlike butyrolactone V (3) suggesting them as plausible chemical entities for developing lead molecules. [ABSTRACT FROM AUTHOR]

Five undescribed butenolides including two pairs of enantiomers, (+)-asperteretal G (1a), (−)-asperteretal G (1b), (+)-asperteretal H (2a), (−)-asperteretal H (2b), asperteretal I (3), and para-hydroxybenzaldehyde derivative, (S)-3-(2,3-dihydroxy-3-methylbutyl)-4-hydroxybenzaldehyde (14), were isolated together with ten previously reported butenolides 4–13, from the coral-derived fungus Aspergillus terreus SCSIO41404. Enantiomers 1a/1b and 2a/2b were successfully purified by high performance liquid chromatography (HPLC) using a chiral column, and the enantiomers 1a and 1b were new natural products. Structures of the unreported compounds, including the absolute configurations, were elucidated by NMR and MS data, optical rotation, experimental and calculated electronic circular dichroism, induced circular dichroism, and X-ray crystal data. The isolated butenolides were evaluated for antibacterial, cytotoxic, and enzyme inhibitory activities. Compounds 7 and 12 displayed weak antibacterial activity, against Enterococcus faecalis (IC50 = 25 μg/mL) and Klebsiella pneumoniae (IC50 = 50 μg/mL), respectively, whereas 6 showed weak inhibitory effect on acetylcholinesterase. Nevertheless, most of the butenolides showed inhibition against pancreatic lipase (PL) with an inhibition rate of 21.2–73.0% at a concentration of 50 μg/mL. [ABSTRACT FROM AUTHOR]

The biological screening of 44 marine sponge extracts for the research of bioactive molecules, with potential application in the treatment of age-related diseases (cancer and Alzheimer's disease) and skin aging, resulted in the selection of Scopalina hapalia extract for chemical study. As no reports of secondary metabolites of S. hapalia were found in the literature, we undertook this research to further extend current knowledge of Scopalina chemistry. The investigation of this species led to the discovery of four new compounds: two butenolides sinularone J (1) and sinularone K (2), one phospholipid 1-O-octadecyl-2-pentanoyl-sn-glycero-3-phosphocholine (3) and one lysophospholipid 1-O-(3-methoxy-tetradecanoyl)-sn-glycero-3-phosphocholine (4) alongside with known lysophospholipids (5 and 6), alkylglycerols (7–10), epidioxysterols (11 and 12) and diketopiperazines (13 and 14). The structure elucidation of the new metabolites (1–4) was determined by detailed spectroscopic analysis, including 1D and 2D NMR as well as mass spectrometry. Molecular networking was also explored to complement classical investigation and unravel the chemical classes within this species. GNPS analysis provided further information on potential metabolites with additional bioactive natural compounds predicted. [ABSTRACT FROM AUTHOR]

Using 1-thioaurones and 1-azaaurones as electron-deficient oxa-dienes, an organocatalytic asymmetric aromatizing inverse electron-demand [4+2] cycloaddition with γ-deconjugated butenolides and azlactones was developed. A wide range of optically active benzothiophene-fused δ-lactones and indole-fused δ-lactones were obtained with desirable outcomes (up to 94% yield, >99 : 1 dr and 99% ee). [ABSTRACT FROM AUTHOR]

An organocatalytic 1,6-addition using 4-(alk-1-en-1-yl)-3-cyanocoumarins as acceptors has been developed. Dienolates derived from 5-substituted-furan-2(3H)-ones have been employed as pronucleophiles, therefore, enabling the synthesis of hybrid molecules bearing two biologically relevant units. Appropriate design of substrates and the application of quinine-derived catalyst resulted in very good site-selectivity as well as chemical and stereochemical efficiency of the process. [ABSTRACT FROM AUTHOR]

A new butenolide derivative (1) featuring octyl substitution at γ-position, together with four known analogues (2–5) were isolated from marine-derived Streptomyces koyangensis SCSIO 5802. The structure of 1 was elucidated by HR-MS and NMR spectroscopic data analyses. The absolute configuration of the stereo centre in lactone ring of 1 was determined by comparison of CD spectrum with those of known compounds. Compound 1 exhibited mild antiviral activity against herpes simplex virus with EC50 value of 25.4 µM. [ABSTRACT FROM AUTHOR]

Asymmetric allylic C – H alkylation of 1,4-pentadienes with α-angelica lactones has been developed by tri-axial phosphoramidite-palladium catalysis. This reaction can tolerate a range of functional groups under mild conditions, furnishing versatile chiral γ,γ-disubstituted butenolides in high yields with good to high levels of stereoselectivity. [ABSTRACT FROM AUTHOR]

An iron‐catalyzed three‐component cyanoalkylsulfonylation of 2,3‐allenoic acids, K2S2O5, and the ring‐opening of cyclobutanone oxime esters is described. The radical tandem cyclization route allows access to diverse cyanoalkylsulfonylated butenolides in moderate to good yields under mild conditions. Moreover, the products are further converted, offering the corresponding derivatives. [ABSTRACT FROM AUTHOR]

Two new butenolides, balanolides A (1) and B (1), were isolated from the aerial parts of the parasitic plant Balanophora fungosa. Their structures were established by comprehensive spectroscopic analysis and quantum chemical ECD calculation. The new butenolides were evaluated for their inhibitory effects against nitric oxide (NO) production in LPS-induced RAW 264.7 macrophage cells. Compounds 1 and 2 displayed moderate anti-inflammatory activity with IC50values of 11.8 and 12.9 μM, respectively. [ABSTRACT FROM AUTHOR]

Summary: Strigolactones and karrikins are butenolide molecules that regulate plant growth. They are perceived by the α/β‐hydrolase DWARF14 (D14) and its homologue KARRIKIN INSENSITIVE2 (KAI2), respectively. Plant‐derived strigolactones have a butenolide ring with a methyl group that is essential for bioactivity. By contrast, karrikins are abiotic in origin, and the butenolide methyl group is nonessential. KAI2 is probably a receptor for an endogenous butenolide, but the identity of this compound remains unknown.Here we characterise the specificity of KAI2 towards differing butenolide ligands using genetic and biochemical approaches.We find that KAI2 proteins from multiple species are most sensitive to desmethyl butenolides that lack a methyl group. Desmethyl‐GR24 and desmethyl‐CN‐debranone are active by KAI2 but not D14. They are more potent KAI2 agonists compared with their methyl‐substituted reference compounds both in vitro and in plants. The preference of KAI2 for desmethyl butenolides is conserved in Selaginella moellendorffii and Marchantia polymorpha, suggesting that it is an ancient trait in land plant evolution.Our findings provide insight into the mechanistic basis for differential ligand perception by KAI2 and D14, and support the view that the endogenous substrates for KAI2 and D14 have distinct chemical structures and biosynthetic origins. [ABSTRACT FROM AUTHOR]

Kinetic resolution (KR) and dynamic kinetic resolution (DKR) of γ‐aryl and heteroaryl‐substituted butenolides via CuH‐catalyzed 1,4‐hydroboration using pinacolborane is reported. With a copper‐Ph‐BPE catalyst, selectivity factors were extremely high (s=>400) with regard to the kinetic resolution of β‐methyl‐γ‐phenyl butenolide; DKR was possible in the presence of an amine base (DBU), which facilitated racemization of the starting unsaturated lactones. The reaction provided easy access to highly enantioenriched γ‐butyrolactones (>99% ee) containing β,γ‐substituents. [ABSTRACT FROM AUTHOR]

Design and development of a domino cyclative approach for the synthesis of new polycyclic γ‐butenolides from β‐aryl‐Z‐enoate propargylic alcohols, through the interception of an intermediate of the Z‐enoate‐assisted Meyer–Schuster rearrangement, has been reported. A systematic NMR analysis of various derivatives of this class revealed and supported the potential atropisomerism associated with them. These molecules represent first examples of butenolide ring‐based atropisomeric compounds in organic chemistry. The synthetic process involves a synchronous construction of both rings with concurrent creation of the potential stereogenic rotational axis. [ABSTRACT FROM AUTHOR]

Five undescribed butenolides including two pairs of enantiomers, (+)-asperteretal G (1a), (−)-asperteretal G (1b), (+)-asperteretal H (2a), (−)-asperteretal H (2b), asperteretal I (3), and para-hydroxybenzaldehyde derivative, (S)-3-(2,3-dihydroxy-3-methylbutyl)-4-hydroxybenzaldehyde (14), were isolated together with ten previously reported butenolides 4–13, from the coral-derived fungus Aspergillus terreus SCSIO41404. Enantiomers 1a/1b and 2a/2b were successfully purified by high performance liquid chromatography (HPLC) using a chiral column, and the enantiomers 1a and 1b were new natural products. Structures of the unreported compounds, including the absolute configurations, were elucidated by NMR and MS data, optical rotation, experimental and calculated electronic circular dichroism, induced circular dichroism, and X-ray crystal data. The isolated butenolides were evaluated for antibacterial, cytotoxic, and enzyme inhibitory activities. Compounds 7 and 12 displayed weak antibacterial activity, against Enterococcus faecalis (IC50 = 25 μg/mL) and Klebsiella pneumoniae (IC50 = 50 μg/mL), respectively, whereas 6 showed weak inhibitory effect on acetylcholinesterase. Nevertheless, most of the butenolides showed inhibition against pancreatic lipase (PL) with an inhibition rate of 21.2–73.0% at a concentration of 50 μg/mL.