Lactone Research Articles

Evaluation of Chemical Constituents and Antioxidant Activity of Extracts of Nardostachys jatamansi (D. Don) DC.

Nardostachys jatamansi is an endangered medicinal plant of the Caprifoliaceae family. The main aim of this study was to evaluate the metabolites and their biological activities. The shade dried, powdered plant materials were subjected to successive ultrasonic extraction with solvents hexane, chloroform, ethyl acetate, and methanol in the increasing order of polarity. Flavonoids, terpenoids, saponins, phenolic volatile oils, and alkaloids were discovered in the phytochemical screening. Gas chromatography mass spectrometry analysis identified 13, 10, and 6 chemical compounds in hexane, chloroform, and ethyl acetate extracts, respectively. Cyclic saturated hydrocarbons, organic acids, alcohol, and ester were the main constituents of extracts verified by GC-MS. Chloroform extracts had a higher phenolic content (49.53 mg GAE/g) than ethyl acetate extracts (44.41 mg GAE/g).  Chloroform extracts had a higher total flavonoid concentration (18.42 mg QE/g) than ethyl acetate extracts (10.57 mg QE/g).  The half-maximum inhibitory concentration (IC50) of the chloroform and ethyl acetate extracts revealed moderate results to antioxidant activity.

Identification of compounds and functional groups of n-hexane seed extracts of Citrullus lanatus and Elaeis guineensis using GC-MS and FT-IR

Citrullus lanatus and Elaeis guineensis are regarded as two of the most significant edible fruits in terms of nutrition and medicine. Utilizing FTIR and GC-MS spectroscopy, the current work aims at identifying bioactive compounds and functional groups present in n-hexane seed extracts of Citrullus lanatus and Elaeis guineensis. The GC-MS approach is used to screen and identify phytocompounds. Using a Buck Scientific M530 USA spectrophotometer, the FTIR technique was used to identify the functional groups. Twenty-five (25) and twenty-nine (29) bioactive compounds were identified in Citrullus lanatus and Elaeis guineensis respectively, by Gas Chromatographic-Mass Spectrometry (GC-MS). Linoelaidic acid (58.79%) was the most prevalent compound identified in Citrullus lanatus seed extract. Gamma-tocopherol has the most diverse pharmacological role. n-hexadecanoic acid (16.82%), dodecanoic acid (0.12%), 9, 12-octadecadienoic acid methyl ester (3.45%) and 9, 12-octadecadienoic acid (Z, Z) (0.91%) are some of the other bioactive compounds detected. The most prevalent phytocompound identified in Elaeis guineensis seed extract is dodecanoic acid (37.20%), whereas the most diverse pharmacological activity was found in n-hexadecanoic acid. N-decanoic acid (6.32%), 6-octadecenoic acid (11.95%), octanoic acid (5.27%) and tetradecanoic acid (17.59%) are some other bioactive compounds identified. Ether, ethene, primary amine, carboxylic acid, cyclic ester, nitrile, methylene, primary, secondary and tertiary alcohols were detected at various wavelengths in both seed extracts by Fourier transform infrared (FTIR) spectrophotometer. Both extracts contain phytocompounds with antioxidant, anti-inflammatory and antimicrobial properties that are useful in preventing and treating diseases.

Modulation of bacterial infection and inflammation by release of lactide from a silicone elastomer device

The aim of this project is to assess the anti-bacterial and anti-inflammation properties of a matrix-type silicone elastomer device providing sustained release of DL-lactide (a cyclic ester dimer of lactic acid). Lactide-loaded matrices were prepared by injection molding, and the devices were assessed for of in vitro release, anti-bacterial activity, and anti-inflammatory activity. The devices provided sustained release of lactide/lactic acid over five days and were effective against E. coli and S. aureus. Further, the devices reduced inflammation through activation of the GPR81 receptor via the NF-κB and JAK-STAT signalling pathway. These lactide-releasing silicone elastomer devices could improve clinical outcomes with certain short-term medical devices.

Organocatalyzed Synthesis of Bicyclic γ‐Lactam Derivatives via Asymmetric Conjugate Addition of Cyclic β‐Keto Esters to Benzoyl Acrylonitriles

AbstractA diaminomethylenemalononitrile organocatalyst efficiently promoted the asymmetric conjugate addition of cyclic β‐keto esters to benzoyl acrylonitriles to afford the corresponding adducts. This was followed by the transformation of the nitrile group into an amide group, resulting in bicyclic γ‐lactam derivatives in good yields with excellent enantioselectivities (up to 99 % ee). As far as we know, this is the first study to synthesize chiral bicyclic γ‐lactam derivatives from cyclic β‐keto esters and benzoyl acrylonitriles.

Enantioselective (3+2)-Annulation of β-Keto Esters with Azoalkenes towards Bicyclic Dihydropyrroles via Cooperative Palladium and Brønsted Acid Catalysis

AbstractA cooperative catalytic process through palladium and Brønsted acid activation is developed for the conjugate addition of cyclic β-keto esters to azoalkenes directly followed by hemiaminal formation upon cyclization. This transformation is enabled by utilizing chiral Pd-aqua complexes as combined Brønsted acid–base catalysts. Thus, bicyclic and highly functionalized dihydropyrroles with two contiguous quaternary stereogenic centers are formed in excellent yields as single diastereomers and with exceptional enantioselectivity.

Aluminum and titanium complexes bearing 2,6-Bis(2-hydroxyphenyl)pyridines for ring-opening polymerization of lactide, ε-caprolactone and their copolymerization: Effect of a ligand on coordination chemistry and reactivity

In ring-opening polymerization (ROP) of cyclic esters, the rational design of the catalyst is generally applied to solve the task of providing polyester biocompatibility (non-toxicity) and the problem of copolymer homogeneity when using comonomers of different nature (e. g. lactones and lactides). In the present work, we report the synthesis of aluminum and titanium complexes, based on substituted 2,6-bis(2-hydroxyphenyl)pyridine pro-ligands 1 and 2. It was found that the structure of the pro-ligand drastically affect the structure of the reaction product. Pro-ligand 2 with a bulky tert‑butyl group leads to the monomeric complexes 6 (LAlMe) and 7 (LTi(OiPr)2), while the ligands with less bulky groups lead to the oligomeric Al-containing compounds 3 and 4, and in the case of Ti bis-ligand complex 5 is formed. Complexes 6 (in presence of BnOH) and 7 turned out to be active in the ROP of ε-caprolactone and l-lactide and gave PCL and PLA with high molecular masses. Compound 6 was an effective initiator of copolymerization of ε-caprolactone and l-lactide which led to statistical copolymer poly(LA-stat-CL) with comonomer subunits ratio of 1:1.

Leaf Extracts of Invasive Woody Species Demonstrate Allelopathic Effects on the Growth of a Lawn Grass Mixture.

Biochemical composition was studied in the leaf litter of alien woody species included in the 100 most aggressive invasive species of Europe: Ailanthus altissima, Quercus rubra, Acer negundo, Robinia pseudoacacia, and Elaeagnus angustifolia. Using GC-MS, we detected 187 metabolites in the leaf litter, which are phenolic acids and their derivatives, carbohydrates and their derivatives, polyphenolic compounds, cyclic esters, glycosides, and amino acids and their derivatives. Species-specific metabolites were identified for each species. The main allelochemicals in the leaf litter extract of Q. rubra are determined mainly by the relative abundance of phenolic and fatty acids and their esters, whereas those in the leaf litter extract of R. pseudoacacia are determined by carbohydrates and their derivatives and ester of fatty acid, and those in the leaf litter extract of A. altissima are determined by glycosides. Profiles of macro- and microelements were characterized. It was found that aqueous extracts of leaf litter from all the invasive woody plants under study have a negative effect on the seed germination and initial growth of Vicia cracca and Avena strigosa used for the reclamation of disturbed urban and industrial lands. At the same time, V. cracca is potentially more sensitive.

Amidative Cyclization of Alkynyl Esters to Access Pyrazin-1(2H)-ones: Application to the Synthesis of Peramine and Dibromophakellin.

Herein, we report an efficient 1,5,7-Triazabicyclo[4.4.0]dec-5-ene (TBD)-catalyzed tandem intermolecular amidation and regioselective intramolecular 6-exo-dig cyclization of alkynyl esters to efficiently access pyrazine-1(2H)-one scaffolds. This organo-catalyzed [5 + 1] annulation features a broad substrate scope concerning both annulating partners. Total syntheses of peramine and formal syntheses of dibromophakellin natural products were achieved to show the application potential of the method.

Enantio- and Diastereoselective Copper-Catalyzed Synthesis of Chiral Aziridines with Vicinal Tetrasubstituted Stereocenters.

A Cu-catalyzed coupling of cyclic imino esters with 2H-azirines has been developed to synthesize novel optically active aziridines in high yields with excellent levels of diastereo- and enantioselectivities under mild conditions. This novel protocol features a broad substrate scope and good functional group compatibility, and it enriches the existing reaction type of rapid synthesis of optically active aziridines bearing vicinal tetrasubstituted stereogenic carbon centers.

A DNA-polymer hybrid nanocomplex based bi-adjuvant vaccine for tumor immunotherapy

The immunosuppressive tumor microenvironment (TME) seriously impedes the cancer immunotherapy; Toll-like receptors (TLRs) agonists combination is emerging as vaccine adjuvant in reprogramming tumor immune microenvironment. Herein, we develop a supramolecular DNA-polymer hybrid nanocomplex-based bi-adjuvant vaccine for tumor immunotherapy. In the nanocomplex, the co-assembly of TLR9 agonist (CpG) and TLR7 agonist (loxoribine) was achieved via dynamic DNA assembly and boron chemistry. Poly-N-isopropyl acrylamide (PNIPAM) served as the framework of the nanocomplex, and meanwhile, designer DNA sequences were introduced as cross-linkers in the nanoframework to trigger the hybridization chain reaction (HCR)-based assembly of CpG sequences containing hairpins. The polymer framework was decorated with phenylboronic acid to capture and release loxoribine via reversible formation of cyclic boric acid ester. A lipid shell was coated on the outside of the CpG and loxoribine co-loaded nanocomplex to prevent the leakage of loxoribine in plasma. After intravenous injection, the nanocomplex was internalized by the tumor-associated immune cells via lysosomal related pathways. CpG and loxoribine synergistically stimulated TLR9 and TLR7 receptors, thus leading to the conversion of suppressive M2 macrophage to active M1 macrophage, maturation of dendritic cells, and activation of T cells. The dual activation of TLR9 and TLR7 effectively reprogramed tumor immune microenvironments in vivo, wherein robust CD8+ T cell response and efficient tumor regression were achieved. This work provides a unique design concept for the TLR agonists combination-based nanovaccine for tumor immunotherapy.

Ring-Opening Polymerization of rac-β-Butyrolactone Promoted by New Tetradentate Thioether-Amide Ligand-Type Zinc Complexes.

In this work, thioether-amide ligands featuring a combination of hard amide groups with soft donor groups have been employed to develop new zinc catalysts for the ring-opening polymerization of cyclic esters. All complexes were prepared in high yields through alkane elimination reactions with diethyl zinc and characterized using nuclear magnetic resonance (NMR) spectroscopy. Density functional theory (DFT) characterization provided insight into the parameters that influence catalytic activity, such as steric hindrance at the metal center, Lewis acidity and electronic density of thioether-amide ligands. In the presence of one equivalent of isopropanol, all complexes were active in the ring-opening polymerization of rac-β-butyrolactone. Quantitative conversion of 100 monomer equivalents was achieved within 1 h at 80 °C in a toluene solution. Number-average molecular weights increased linearly with monomer conversion; the values were in optimal agreement with those expected, and polydispersity index values were narrow and relatively constant throughout the course of polymerization. The most active complex was also effective in the ring-opening polymerization of ε-caprolactone and L-lactide. To propose a reliable reaction path, DFT calculations were undertaken. In the first step of the reaction, the acidic proton of the alcohol is transferred to the basic nitrogen atom of the amide ligand coordinated to the zinc ion. This leads to the alcoholysis of the Zn-N bond and the formation of an alcoholate derivative that starts the polymerization. In subsequent steps, the reaction follows the classical coordination-insertion mechanism.

Development, characterization, and consumer acceptance evaluation of thermally stable capsule beads containing mixed extracts of green tea and turmeric

The aim of this study was to investigate the ability of shell (coating) formulations comprised of alginate and glucono delta lactone (GDL) to encapsulate a mixture of green tea and turmeric extracts. Three concentrations of alginate and GDL were used at 0.5%, 0.75%, and 1%, w/v and their solid ratio was varied using a factorial design. A response surface model was applied to optimize the retention of catechin and curcuminoid contents, to determine encapsulation efficiency, and to minimize undesirable flavor and taste. Increasing the concentration of alginate and GDL significantly increased the retention of catechin and curcuminoid contents, encapsulation efficiency, and consumer acceptance (p < 0.05). The encapsulating solution containing 1% of each alginate and GDL performed the best against each criterion. The thermal treatment carried out at the boiling point of water for 15 min had a significant impact on the retention of catechin and curcuminoid content which, in the thermally-treated beads, was 5.15 and 3.85 times higher than unencapsulated, respectively. The consumer acceptance of the encapsulated beads after thermal treatment was higher than that of the unencapsulated formulations as they exhibited lesser pungent flavor and bitterness. The innovative process of thermally stable microencapsulation can produce anti-cancer activity compounds involved in functional food industrial sectors.

Green synthesis of 2-trifluoromethyl quinoline derivatives under metal-free conditions and their antifungal properties

The skeleton of 2-trifluoromethyl quinoline is the core structure of many natural products and pharmaceutical molecules. The synthesis of this scaffold is limited by metal catalysis, harsh conditions, toxic or hazardous reagents and solvents, and lower atom-economy. Herein, a novel method for the synthesis of 2-trifluoromethyl quinolines via the [4 + 2] cyclization of β-keto esters or 1,3-diketones with various substituted o-aminobenzaldehydes using the metal free catalyst in EtOH is reported. This atom- and step-economical protocol features simple operation, broad substrate scope, and good functional-group compatibility. The synthetic utility of this methodology was highlighted by easy gram-scale synthesis and late-stage functionalization, which would promote the vigorous development of quinoline chemistry. Moreover, the in vitro antifungal activities of the 2-trifluoromethyl quinolines against F. graminearum (from wheat), F. graminearum (from corn), F. moniliforme, F. oxysporum, and R. solani were investigated to further potential utility of these compounds.

Advances in cyclic ester ring‐opening polymerization using heterogeneous catalysts

Aliphatic polyesters' propensity to be biocompatible and biodegradable, as well as their prospective applications in the medical and agricultural industries, has prompted much research into their synthesis. As ring‐opening polymerization (ROP) technology has advanced rapidly, the invention of discrete, thoroughly characterized heterogeneous catalysts, which are potent polymerization initiators for ROP, has received much attention during the last decade. Numerous polyester microstructures have been produced because of recent developments in the catalyst design of new heterogeneous catalysts and applied in initiating the ROP of cyclic esters. This study reviewed the ROP of cyclic ester catalysts composed of a heterogenous catalyst such as metal–organic frameworks (MOFs) and supported catalyst. MOFs are crystalline porous materials with tunable frameworks that make them potential mediums for polymerization. The MOF structure's precise design is important to control polymerizations because it provides control over both primary and higher‐order structures. Additionally, the stability of the heterogeneous catalyst is also discussed. Finally, the conclusion to the previous study and a stance for future prospects is given. This article intends to provide valuable information for building a heterogeneous catalyst for the ROP of cyclic esters with enhanced activity.

Metal Complexes in the Synthesis of Biodegradable Polymers: Achievements and Prospects.

This review describes recent advances in the synthesis of homopolymers of lactide and related cyclic esters via ring-opening polymerization (ROP) in the presence of metal complexes based on group 1, 2, 4, 12, 13 and 14 metals. Particular attention is paid to the influence of the initiator structure on the properties of the obtaining homo- and copolymers. Also, a separate chapter is devoted to the study of metal complexes in the synthesis of copolymers of lactide and lactones. This review highlights the efforts made over the last ten years or so, and shows how main-group metals have received increasing attention in the field of the polymerization of lactide and related cyclic esters.

Tetrabutylammonium Halides as Selectively Bifunctional Catalysts Enabling the Syntheses of Recyclable High Molecular Weight Salicylic Acid‐Based Copolyesters

AbstractTo synthesize high molecular weight poly(phenolic ester) via a living ring‐opening polymerization (ROP) of cyclic phenolic ester monomers remains a critical challenge due to serious transesterification and back‐biting reactions. Both phenolic ester bonds in monomer and polymer chains are highly active, and it is difficult so far to distinguish them. In this work, an unprecedented selectively bifunctional catalytic system of tetra‐n‐butylammonium chloride (TBACl) was discovered to mediate the syntheses of high molecular weight salicylic acid‐based copolyesters via a living ROP of salicylate cyclic esters (for poly(salicylic methyl glycolide) (PSMG), Mn=361.8 kg/mol, Ð&lt;1.30). Compared to previous catalysis systems, the side reactions were suppressed remarkably in this catalysis system because phenolic ester bond in monomer can be selectively cleaved over that in polymer chains during ROP progress. Mechanistic studies reveal that the halide anion and alkyl‐quaternaryammonium cation work synergistically, where the alkyl‐quaternaryammonium cation moiety interacts with the carbonyl group of substrates via non‐classical hydrogen bonding. Moreover, these salicylic acid‐based copolyesters can be recycled to dimeric monomer under solution condition, and can be recycled to original monomeric monomers without catalyst under sublimation condition.

Tetrabutylammonium Halides as Selectively Bifunctional Catalysts Enabling the Syntheses of Recyclable High Molecular Weight Salicylic Acid-Based Copolyesters.

To synthesize high molecular weight poly(phenolic ester) via a living ring-opening polymerization (ROP) of cyclic phenolic ester monomers remains a critical challenge due to serious transesterification and back-biting reactions. Both phenolic ester bonds in monomer and polymer chains are highly active, and it is difficult so far to distinguish them. In this work, an unprecedented selectively bifunctional catalytic system of tetra-n-butylammonium chloride (TBACl) was discovered to mediate the syntheses of high molecular weight salicylic acid-based copolyesters via a living ROP of salicylate cyclic esters (for poly(salicylic methyl glycolide) (PSMG), Mn =361.8 kg/mol, Ð<1.30). Compared to previous catalysis systems, the side reactions were suppressed remarkably in this catalysis system because phenolic ester bond in monomer can be selectively cleaved over that in polymer chains during ROP progress. Mechanistic studies reveal that the halide anion and alkyl-quaternaryammonium cation work synergistically, where the alkyl-quaternaryammonium cation moiety interacts with the carbonyl group of substrates via non-classical hydrogen bonding. Moreover, these salicylic acid-based copolyesters can be recycled to dimeric monomer under solution condition, and can be recycled to original monomeric monomers without catalyst under sublimation condition.

Quinolyl/pyridyl-amino Li complexes as dual catalysts for the ring-opening polymerization of cyclic esters and degradation toward a circular economy approach

Bi- and tetra-lithium quinolyl/pyridyl-amino complexes 1–4 were synthesized and characterized. These lithium complexes were capable of initiating the polymerization of rac-lactice (rac-LA) and ε-caprolactone (ε-CL) with high catalytic activity, respectively, whether in the presence or absence of BnOH. Both number of metal centers and ligand structures are identified as the crucial factors that determine the reactivity of a catalyst in the ROP. Their kinetic analyses indicated that tetrametallic complex 3 showed a more cooperativity comparable to that achieved with bimetallic analogues in the ring-opening polymerization (ROP) of ε-CL, however, number of metal centers has no obvious effect on catalytic activity for the ROP of rac-LA. Polymer end-group analysis by 1H NMR and MALDI-TOF MS support the reaction initiated by Li complexes without or with BnOH switching mechanism from a coordination-insertion to an active monomer in the ROP processes reasonably. The diblock copolymer PCL-b-PLA can be effectively prepared by polymerizing ε-CL firstly followed by addition of rac-LA. However, the formation of PLA-b-PCL or PLA-random-PCL is limited, and the resulting copolymers only contain a short sequence of PCL moieties which produced by the transesterification between PLA and ε-CL, whether the two monomers are added sequentially or simultaneously. Interestingly, these Li complexes not only exhibit a high activity for the polymerization of PLA, but also can fully degrade the resultant PLA into methyl lactate (Me-La) in the presence of MeOH, which is a rare example of making or breaking polymer for chemical recycling.

Mitigation of hydrocarbon toxicity using bacterial consortium in microcosm environment for agrarian fecundity

Petroleum contamination in the soil has been well emphasized as a toxic and hazardous soil pollution contributing to a significant portion of soil infertility worldwide. In the present study, bacterial consortium CHM1 composed of 5 strains belonging to genera Klebsiella, Pantoea, and Enterobacter was evaluated for hydrocarbon degradation ability in the soil environment, as well as their performance in remediating ecotoxicity and phytotoxicity. Initially, the degradation efficiency (1.98%/day) in the soil environment was evaluated. Scanning Electron Microscopy combined with Energy Dispersive X-ray spectroscopy revealed an increase in nitrogen content by 24.98% and a decrease in carbon content by 22.76% implying an improvement in soil fertility. The Fourier Transform InfraRed spectroscopy and Gas Chromatographic analysis revealed significant depletion of aromatic, cyclic, long aliphatic, and complex acid and ester content of the test soil. Moreover, the quantitative PCR analysis exhibited the non-competitive coexistence of each component of the CHM1 consortium. Different enzymatic assays revealed elevated dehydrogenase and superoxide dismutase activity in the degradation system due to the introduction of CHM1 in the soil microcosm. Vibrio fischeri-assisted ecotoxicity analysis had established the potential of CHM1 to efficiently minimize the ecotoxicity of hydrocarbon contamination. The phytotoxicity analysis was performed using four different plant models viz. Chickpeas (Cicer arientinum), Coriander (Coriandrum sativum), Fenugreek (Trigonella foenum-graecum), and Spinach (Spinacia oleracea) exhibiting CHM1 amendment helped to restore plant germination and growth in hydrocarbon-contaminated soil system efficiently. The promising results from this study indicated the possible application of the bacterial consortium in hydrocarbon-contaminated land management and soil restoration for cultivation or other plantation purposes.

Recent investigations in synthesis of oxathiazinanes by sulfamate ester cyclization (microreview)

Recent investigations in synthesis of oxathiazinanes by sulfamate ester cyclization (microreview)