Lactone Structure Research Articles

Deciphering the key drivers of oxidative potential during ammonium nitrate-mediated aqueous-phase photoreaction of methoxyphenols

Methoxyphenols are released in abundance from lignin pyrolysis during biomass burning. Apart from being atmospheric brown carbon components that absorb solar radiation and warm the climate, methoxyphenols also undergo photoreaction in the atmospheric aqueous phase and form secondary organic aerosols (aqSOA). While efforts have been devoted to understanding chemical evolutions and climate-related optical properties of aqSOA, their potential health impacts also require timely investigations. Herein, we used the dithiothreitol (DTT) assay to investigate oxidative potential of the aqSOA formed during the 8-hr aqueous-phase photoreaction of two typical methoxyphenols, vanillin and vanillic acid, under pH 2 or 8, and with or without ammonia nitrate. The highest DTT consumption rates (RDTT) were observed for vanillin aqSOA formed in the presence of ammonia nitrate and at pH 8. At pH 2, although RDTT increased rapidly during early photoreaction, it reduced after prolonged illumination. High resolution mass spectrometry and linear regression analyses were performed to correlate the photoreaction products with the observed RDTT. Results showed that three products that present quinone, lactone and dimer structures, respectively, should be the key drivers of elevated RDTT for aqSOA formed during photoreaction of vanillin and vanillic acid alone, whereas it shifted to the nitrogen-containing aromatic compounds during their photoreaction with ammonia nitrate. Our results have revealed the role of nitrogen-containing aromatic compounds in the oxidative potential and health effects of aqSOA from biomass burning, which was rarely recognized before and warrants immediate assessments.

Progress in the Study of Chemical Structure and Pharmacological Effects of Total Paeony Glycosides Isolated from Radix Paeoniae Rubra.

Radix paeoniae rubra, known as red peony root, is derived from the dried roots of Paeonia lactiflora pall or Paeonia veitchii lynch from the Ranunculaceae family. It is recognized for its properties of clearing heat, cooling blood, dispelling stasis, and alleviating pain, making it one of the most commonly used herbs in traditional Chinese medicine. Total paeony glycosides (TPGs) are identified as the principal active constituents of Radix paeoniae rubra, comprising monoterpenoid compounds with a cage-like pinane structure and monoterpenoids with a lactone structure. This review summarizes the chemical constituents and pharmacological effects of TPGs, with the aim of elucidating their relationships.

Construction of Six-Membered Lactam and Lactone Structures via Ligand-Free Pd-Catalyzed C-H Activation/[5 + 1] Cyclization Carbonylation.

An approach for the ligand-free Pd-catalyzed C-H activation/[5 + 1] cyclization carbonylation by employing readily available ClCF2COONa as a carbonyl source via difluorocarbene transfer and hydrolysis has been developed. The current protocol enables us to obtain a series of carbonylation cyclization product benzopyranone and phenanthridinone derivatives in up to 91% yield with excellent functional group compatibility. This protocol has the advantages of mild reaction conditions, wide applicable substrates, and simple and safe operation and provides a new method for the synthesis of complex lactam and lactone compounds.

Unraveling Stereochemical Structure-Activity Relationships of Sesquiterpene Lactones for Inhibitory Effects on STAT3 Activation.

Sesquiterpene lactones, a class of natural compounds abundant in the Asteraceae family, have gained attention owing to their diverse biological activities, and particularly their anti-proliferative effects on human cancer cells. In this study, we systematically investigated the structure-activity relationship of ten sesquiterpene lactones with the aim of elucidating the structural determinants for the STAT3 inhibition governing their anti-proliferative effects. Our findings revealed a significant correlation between the STAT3 inhibitory activity and the anti-proliferative effects of sesquiterpene lactones in MDA-MB-231 breast cancer cell lines. Among the compounds tested, alantolactone and isoalantolactone emerged as the most potent STAT3 inhibitors, highlighting their potential as candidates for anticancer drug development. Through protein-ligand docking studies, we revealed the structural basis of STAT3 inhibition by sesquiterpene lactones, emphasizing the critical role of hydrogen-bonding interactions with key residues, including Arg609, Ser611, Glu612, and Ser613, in the SH2 domain of STAT3. Furthermore, our conformational analysis revealed the decisive role of the torsion angle within the geometry-optimized structures of sesquiterpene lactones in their STAT3 inhibitory activity (R=0.80, p<0.01). These findings not only provide preclinical evidence for sesquiterpene lactones as promising phytomedicines against diseases associated with abnormal STAT3 activation, but also highlight the importance of stereochemical aspects in their activity.

Torrefaction: A promising approach for the harmless treatment of low-moisture tetracycline mycelial residue

Tetracycline mycelial residue (TMR), a byproduct derived from the tetracycline fermentation process, is rich in organic matter, making it a promising resource. However, the presence of residual tetracycline and antibiotic resistance genes (ARGs) limits its potential for resource utilization. In this study, torrefaction was employed for the harmless treatment of low-moisture TMR, and the optimized condition was 200.0 °C for 30.0 min. Under this condition, 97.2% of tetracycline (TC) in TMR could be efficiently removed, with more organic matter reserved for resource utilization. The plausible degradation pathway was proposed, involving the formation of lactone structure and anhydro-tetracycline (ATC) during TC degradation, followed by a series of reactions among main functional groups, including concerted reactions, retro-Diels-Alder (RDA), cleavage reactions, and rearrangement. Furthermore, the antibacterial efficacy of degradation products from TC has significantly diminished, and the structure of ARGs and bacteria was disrupted during the torrefaction of TMR. After the treated TMR was amended into the soil as fertilizer, the dissemination of ARGs could also be effectively controlled. Therefore, torrefaction could be recommended as a promising harmless treatment for the resource utilization of low-moisture TMR.

The chromosome-scale assembly of the Notopterygium incisum genome provides insight into the structural diversity of coumarins

Coumarins, derived from the phenylpropanoid pathway, represent one of the primary metabolites found in angiosperms. The alignment of the tetrahydropyran (THP) and tetrahydrofuran (THF) rings with the lactone structure results in the formation of at least four types of complex coumarins. However, the mechanisms underlying the structural diversity of coumarin remain poorly understood. Here, we report the chromosome-level genome assembly of Notopterygium incisum, spanning 1.64 Gb, with a contig N50 value of 22.7 Mb and 60,021 annotated protein-coding genes. Additionally, we identified the key enzymes responsible for shaping the structural diversity of coumarins, including two p-coumaroyl CoA 2′-hydroxylases crucial for simple coumarins basic skeleton architecture, two UbiA prenyltransferases responsible for angular or linear coumarins biosynthesis, and five CYP736 cyclases involved in THP and THF ring formation. Notably, two bifunctional enzymes capable of catalyzing both demethylsuberosin and osthenol were identified for the first time. Evolutionary analysis implies that tandem and ectopic duplications of the CYP736 subfamily, specifically arising in the Apiaceae, contributed to the structural diversity of coumarins in N. incisum. Conclusively, this study proposes a parallel evolution scenario for the complex coumarin biosynthetic pathway among different angiosperms and provides essential synthetic biology elements for the heterologous industrial production of coumarins.

Structural Transformation of Azonia[5]helicene Photoproduct via Reaction Field Function of Layered Inorganic Material.

In an attempt to generalize "on surface synthesis", which has unique potential in the area of organic synthesis, the focus was placed on layered silicates having a highly flat surface. The photoreaction of (±)-13-bromo-6a-azonia[5]helicene (AHHBr) and (±)-2-bromo-13-methyl-6a-azonia[5]helicene (AHBrMe) in solution and within the layers was examined. In the case of AHBrMe, the photoproduct was different from that in solution. 1H nuclear magnetic resonance (NMR), Fourier transform-infrared spectroscopy (FT-IR), and electrospray ionization-mass spectrometry (ESI-MS) measurements revealed that the photoproduct obtained within the layers was a benzo-perylene molecule with a completely flat lactone structure (AL). This study is the first example of the successful conversion of a chemical reaction path due to the steric effect of the flat surface of layered silicate.

Enzymatic Assembly of Diverse Lactone Structures: An Intramolecular C-H Functionalization Strategy.

Lactones are cyclic esters with extensive applications in materials science, medicinal chemistry, and the food and perfume industries. Nature's strategy for the synthesis of many lactones found in natural products always relies on a single type of retrosynthetic strategy, a C-O bond disconnection. Here, we describe a set of laboratory-engineered enzymes that use a new-to-nature C-C bond-forming strategy to assemble diverse lactone structures. These engineered "carbene transferases" catalyze intramolecular carbene insertions into benzylic or allylic C-H bonds, which allow for the synthesis of lactones with different ring sizes and ring scaffolds from simple starting materials. Starting from a serine-ligated cytochrome P450 variant previously engineered for other carbene-transfer activities, directed evolution generated a variant P411-LAS-5247, which exhibits a high activity for constructing a five-membered ε-lactone, lactam, and cyclic ketone products (up to 5600 total turnovers (TTN) and >99% enantiomeric excess (ee)). Further engineering led to variants P411-LAS-5249 and P411-LAS-5264, which deliver six-membered δ-lactones and seven-membered ε-lactones, respectively, overcoming the thermodynamically unfavorable ring strain associated with these products compared to the γ-lactones. This new carbene-transfer activity was further extended to the synthesis of complex lactone scaffolds based on fused, bridged, and spiro rings. The enzymatic platform developed here complements natural biosynthetic strategies for lactone assembly and expands the structural diversity of lactones accessible through C-H functionalization.

Natural Acceptor of Coumarin-Isomerized Red-Emissive BioAIEgen for Monitoring Cu2+ Concentration in Live Cells via FLIM.

Artificial aggregation-induced emission luminogens (AIEgens) have flourished in bio-applications with the development of synthetic chemistry, which however are plagued by issues like singularity in structures and non-renewability. The unique structures and renewability of biomass moieties can compensate for these drawbacks, but their properties are hard to design and regulate due to their confined structures. Therefore, it appears to be a reasonable approach to derive AIEgens from abundant biomass (BioAIEgens), integrating the bilateral advantages of both synthetic and natural AIEgens. In this work, the blue-violet emissive coumarin with its lactone structure serving as a rare natural acceptor, is utilized to construct donor-π-acceptor typed BioAIE isomers incorporating the propeller-like and electron-donating triphenylamine (TPA) unit. The results show that Cm-p-TPA undergoes charge transfer with its keto form, emitting red light at 600nm, which can be applied to monitor Cu2+ concentration during mitophagy using fluorescence lifetime imaging microscopy because of the excellent biocompatibility, photostability, and specific recognition to Cu2+ . This work not only demonstrates the feasibility of utilizing positional isomerization to modulate excited-state evolutions and resultant optical properties, but also provides evidence for the rationality of constructing biologically-active BioAIEgens via a biomass-derivatization concept.

Detoxification of aflatoxin B1 by Bacillus aryabhattai through conversion of double bond in terminal furan.

This study aimed to screen a bacterial strain with high detoxifying capability for aflatoxin B1 (AFB1), verify its biotransformation efficiency, and detoxification process. Three hundred and fifty samples collected from different environmental niche were screened using coumarin as the sole carbon source. HPLC was used to detect residues of AFB1, and 16S rRNA sequencing was performed on the isolated strain with highest AFB1 removal ratio for identification. The detoxified products of this strain were tested for toxicity in E. coli as well as LO2, Caco-2 and HaCaT human cell lines. HPLC-MS was applied to further confirm AFB1 removal and detoxification process. We identified a strain from plant leaf designated as DT with high AFB1-detoxifying ability that is highly homologous to Bacillus aryabhattai. The optimum detoxification conditions of this strain were 37°C and pH 8.0, resulting in 82.92% removal ratio of 2μg mL-1 AFB1 in 72h. The detoxified products were nontoxic for E. coli and significantly less toxic for the LO2, Caco-2 and HaCaT human cell lines. HPLC-MS analysis also confirmed the significant drop of the AFB1 characteristic peak. Two possible metabolic products, C19H15O8 (m/z 371) and C19H19O8 (m/z 375), were observed by mass spectrometry. Potential biotransformation pathway was based on the cleavage of double bond in the terminal furan of AFB1. These generated components had different chemical structures with AFB1, manifesting that the attenuation of AFB1 toxicity would be attributed to the destruction of lactone structure of AFB1 during conversion process.

Regiospecific and Enantiospecific Effects of the β-Benzyl-α-benzylidene-γ-butyrolactone Structure on Phytotoxic Fungi

Novel derivatives of E-β-benzyl-α-benzylidene-γ-butyrolactone (3-benzyl-2-benzylidene-4-butanolide) with lignano-9,9'-lactone structures were developed as anti-phytopathogenic fungal compounds. Their regiospecific and enantiospecific characteristics were determined, with the E-form and 3R-configuration showing higher activities against the Alternaria alternata Japanese pear pathotype. By the syntheses of benzyl compounds instead of benzylidene and aromatic derivatives, followed by an bioassay experiment, the importance of the benzylidene structure and effects of the substituents of the aromatic ring were clarified. The (2-OCH3, 4'-CH3/4'-CF3)-derivatives, 19 and 25, and (2-OCH3, 6-CH3/6-F/6-Br, 4'-OCH3)-derivatives, 34, 38, and 42, were more effective with EC50 values of 0.1-0.3 μM. It was assumed that the 2-OCH3 group, a hydrophobic group at the 6-position, and some size of the hydrophobic group at the 4'-position were necessary for the increased activity.

Synthesis of isochromanones and benzoxepinones by palladium catalyzed cyclocarbonylation reactions

Heterocyclic compounds such as lactones, lactams or pyrrolidinones are employed as useful intermediates for the synthesis of biologically active products. In the past decades various preparation routes to these class of heterocycles have been described and palladium-based compounds have been regarded as the most efficient catalysts for the preparation of important cyclic compounds. In this work, novel isochromanome and benzoxepinone derivatives have been prepared and fully characterized by nuclear magnetic resonance (NMR) and Fourier transform infrared (FT-IR) spectroscopies and gas chromatography–mass spectrometry (GC–MS) analysis. An effective homogeneous catalytic system based on palladium complex was used. Isochromanone and benzoxepinone derivatives have been synthesized through selective cyclocarbonylation reactions respectively of 2-vinylbenzylalcohols and 2-alkynylbenzylalcohols under syn-gas condition using Pd(OAc)2-dppb as the catalytic system. Depending on the subtrate, different lactone structures were obtained with a good selectivity for each reaction.

Recent advances in organocatalytic cascade reactions for enantioselective synthesis of chiral spirolactone skeletons

Chiral spirolactones, including spiropropyllactones, spirobutyrolactones, and spirovalerolactones, are important heterocyclic frameworks that attracted the attention of organic and medicinal chemists because these motifs constitute the core structure of several natural products and bioactive molecules. The absolute configuration and the substituents on the fully substituted spirocyclic stereocenter of the lactone can potentially enhance specificity for ligand-protein binding and enhance bioavailability, potency, and metabolic stability. So, intensive attention from chemists has been paid to the synthetic methods leading to such prominent structural motifs. The synthetic methods can be divided into two main classes. The first approach takes advantage of the presence of the existing lactone structure and focuses on its functionalization. The second approach is the lactone framework constructed from various precursors in a direct spirolactonization reaction. In this review, for convenience in reading, the recent advances in the synthesis of spirolactones are summarized and discussed according to the two major organocatalytic asymmetric synthetic routes: (i) using the lactone-related frameworks as building blocks; and (ii) direct spirolactonization reaction using various reagents. This review also describes both the mechanisms and related transformations, and gives some insights into challenging issues in this research field, which will enlighten the future development of this field.

New fluorescein dyes with unusual properties: Tetra- and pentanitrofluoresceins

Among various fluorescein dyes, nitro derivatives are less studied. At the same time, these compounds have some unusual properties. This article reports on the behavior of new dyes of this series in solution. Two compounds, 2,4,5,7,4′- and 2,4,5,7,5′-pentanitrofluoresceins, were synthesized, and their molecular structures in the solid state and solution were characterized by X-ray diffraction analysis and NMR spectroscopy. Electronic spectroscopy in dimethyl sulfoxide, DMSO, proves that doubly charged anions of these compounds, R2–, exist in solution in the form of lactone structures, which is not characteristic of other fluorescein dyes. These lactones are yellow (λmax = 420–430 nm) due to the nitrophenolate absorption. On the contrary, singly charged anions are represented predominantly by fluorescent and intensely colored particles with molar absorptivities of (92–96)× 103 M−1cm−1 at λmax = 525 nm, while H2R molecular forms are colorless lactones. The dyes are relatively strong acids; pKa1 and pKa2 values ​​determined in DMSO do not exceed 5 units. It is important to note that in this solvent, as in other media, the pH range of the predominance of HR– monoanions is very narrow. The protolytic equilibrium state of 2,4,5,7-tetranitrofluorescein is similar. The product of the pyran ring rupture of the last-named dye was isolated and identified; this allowed to rationalize the color changes of the parent dye in aqueous solutions within a wide pH range. Of particular interest is the methyl ester of 2,4,5,7-tetranitrofluorescein. The esterification of the carboxyl group avoids lactonization. In contrast to the initial dye, this compound exists as a stable singly charged anion in a wide pH range in all solvents except nonpolar ones, and its fluorescence is very sensitive to the hydrogen bonding ability of the solvent.

Preparation and thermochromic behavior of low-temperature thermochromic microcapsule temperature indicators

Studies have rarely investigated thermochromic materials at refrigeration temperatures (about 8 °C). In this study, such a temperature indicator that can change color at refrigerated temperature was synthesized. Crystal violet lactone (CVL) and lauryl gallate (LG) were dissolved in methyl laurate (ML) at a phase change temperature of 7 °C. A series of low-temperature reversible thermochromic leuco dyes were obtained and used to prepare low-temperature reversible thermochromic microcapsule (TCM) temperature indicators. The FTIR results show that the thermochromic behavior of TCM temperature indicator was determined by LG controlling CVL to open and close the ring for reversible conversion between the lactone structure (colorless) and conjugated structure (colored). The effects of the mass ratio of the three components (wCVL:wLG:wML) on the thermochromic behavior were analyzed according to the CIE Lab chromaticity indexes. The total thermochromic color difference between leuco dye and TCM temperature indicator reached the maximum when the wCVL:wLG:wML was 1:3:125. The TCM temperature indicator gradually changed from dark blue to white from 1 °C to 8 °C. The DSC results show that the decolorization temperature of TCM temperature indicator was very close to the melting point of ML. In addition, microencapsulation prevented the phase separation of leuco dyes and improved the stability of thermochromic materials. The results indicate the enormous potential of TCM temperature indicator for studying thermochromic materials at low temperatures and in temperature monitoring of refrigerated food packages.

A multifunctional fabric with identifiable and controllable surface wettability

With ammonia as the switching link and myristic acid-modified titanium as the raw material, a fabric with synchronous switching of color and wettability was prepared. The unique lactone structure of crystal violet lactone is sensitive to hydrogen bonding in the system. Therefore, after ammonia enters the system, the lactone ring structure is restored, which shows that the color changes from colorfulness to colorless. With the good combination, the fabric can change from superhydrophobicity to superhydrophilicity within 10 s after encountering ammonia, which shows that the color changes from blue to white. In addition, color has a relatively high correspondence with wettability and repeatability. Therefore, the reversible wettability and synchronous blue-to-white color change can provide new ideas for the preparation of materials with controllable wettability.

Hamuramicin C, a Cytotoxic Bicyclic Macrolide Isolated from a Wasp Gut Bacterium.

A new bicyclic macrolide, hamuramicin C (1), was isolated from Streptomyces sp. MBP16, a gut bacterial strain of the wasp Vespa crabro flavofasciata. Its 22-membered macrocyclic lactone structure was determined by NMR and mass spectrometry. The relative configurations of hamuramicin C (1) were assigned by J-based configuration analysis utilizing 1H rotating frame Overhauser effect spectroscopy and heteronuclear long-range coupling NMR spectroscopy. Genomic and bioinformatic analyses of the bacterial strain enabled identification of the type-I polyketide synthase pathway, which employs a trans-acyltransferase system. The absolute configurations of 1 were proposed based on the analysis of the sequences of ketoreductases in the modular gene cluster. Moreover, hamuramicin C (1) demonstrated significant inhibitory activity against diverse human cancer cell lines (HCT116, A549, SNU-638, SK-HEP-1, and MDA-MB-231).

Expanding the Study of the Cytotoxicity of Incomptines A and B against Leukemia Cells.

Heliangolide-type sesquiterpene lactones (HTSLs) are phytocompounds with several pharmacological activities including cytotoxic and antitumor activity. Both bioactivities are related to an α-methylene-γ-lactone moiety and an ester group on carbon C-8 in the sesquiterpene lactone (SL) structure. Two HTSLs, incomptines A (AI) and B (IB) isolated from Decachaeta incompta, were evaluated for their cytotoxic activity on three leukemia cell lines: HL-60, K-562, and REH cells. Both compounds were subjected to a molecular docking study using target proteins associated with cancer such as topoisomerase IIα, topoisomerase IIβ, dihydrofolate reductase, methylenetetrahydrofolate dehydrogenase, and Bcl-2-related protein A1. Results show that IA and IB exhibit cytotoxic activity against all cell lines used. The CC50 value of IA was 2–4-fold less than etoposide and methotrexate, two anticancer drugs used as positive controls. The cytotoxic activity of IB was close to that of etoposide and methotrexate. The molecular docking analysis showed that IA and IB have important interaction on all targets used. These findings suggest that IA and IB may serve as scaffolds for the development of new treatments for different types of leukemia.

Sesquiterpene lactones from Xanthium sibiricum Patrin alleviate asthma by modulating the Th1/Th2 balance in a murine model

BackgroundAsthma is a complex airway disease involving a variety of cells and cytokines. Xanthium sibiricum Patrin ex Widder (X. sibiricum) is a traditional Chinese medicine for various immune diseases, especially allergic rhinitis and asthma. Sesquiterpene lactones are the main bioactive and most abundant constituent, and are characteristic component of the plant. We explore whether sesquiterpene lactones from X. sibiricum (SL-XS) is the main active constitute for its anti-asthma activity. PurposeIn the present study, SL-XS was isolated, the major compounds were isolated and identified in extract of SL-XS, and the anti-asthma activity of SL-XS was validated in vivo. MethodsSL-XS was isolated by a standard phytochemical method. The structures of major sesquiterpene lactones were identified by NMR and LC-MS spectra. The contents of major SL-XS were analyzed by HPLC. The anti-asthma effect of SL-XS was evaluated in a house dust mite (HDM)-induced mouse model. ResultsThe sesquiterpene lactones were isolated from X. sibiricum, and five major constituents i.e., 8‑epi-xanthatin-1β, 5β-epoxide (1), tomentosin (2), 8‑epi-xanthatin (3), 2‑epi-xanthumin (4) and sibiriolide B (5) were identified from SL-XS. Oral administration of SL-XS dose-dependently ameliorated airway inflammation and remodeling in HDM-challenged asthma mouse model. Furthermore, SL-XS treatment inhibited the upregulation of proinflammatory and Th2 cytokines, while reversed the downregulation of Th1 related cytokines. In addition, SL-XS regulated the balance between T-bet and GATA-3. Moreover, SL-XS inhibited the upregulation of JAK1, p-JAK1, JAK2, p-JAK2, JAK3, p-JAK3 and p-STAT6 in HDM-challenged mice. ConclusionThe sesquiterpene lactones including five major constituents may be the main anti-asthma active constituent of X. sibiricum. SL-XS exerted its anti-asthma effect by modulating the Th1/Th2 balance via the JAK/STAT signaling pathway.

Five new diterpenoid alkaloids from Aconitum sczukinii Turcz.

• Five new diterpenoid alkaloids were isolated from Aconitum sczukinii Turcz. • New compound 1 is the first diterpenoid alkaloid that contains a lactone D ring. • A plausible biosynthetic pathway for the formation of 1 is proposed. Ten diterpenoid alkaloids, including five new ones, sczukiniline A–E ( 1 - 5 ), were isolated from the root of Aconitum sczukinii. Their structures were elucidated based on the interpretation of spectroscopic data (HRESI-MS, IR, 1D- and 2D-NMR). Among the five new diterpenoid alkaloids, 1 - 3 are hetidine-type C 20 -diterpenoid alkaloids, while compounds 4 and 5 are lycoctonine-type C 19 -diterpenoid alkaloids. Noteworthily, sczukiniline A ( 1 ) features a novel ester group between C-12 and C-14, forming a D ring containing a lactone structure, resulting in a new skeleton of hetidine-type C 20 -diterpenoid alkaloid.