Olefinic Acids Research Articles

Polyphasic approaches to identify and understand α-glucosidase inhibitory potential of secondary metabolites of Withania coagulans fruit

Withania coagulans (WC) is used in traditional and Ayurveda medicine to treat various ailments, including diabetes. Our investigation found that WC fruit hexane extract effectively suppresses α-glucosidase activity (IC50 = 0.013 mg/ml, Ki = 0.012 mg/ml). The purified molecule has an IC50 of 0.004 mg/ml and Ki of 0.0037 mg/ml. FTIR examination indicates distinctive peaks at 3500, 2900, 1770, and 1500 cm−1 corresponding to functional groups OH bending, CH stretching, CO stretching, and CO stretching. GCMS analysis reveals plant secondary metabolites (PSM) such as n-hexadecenoic acid and methyl 9,10-octadecadienoate. NMR confirms the existence of olefinic fatty acids. The bioactive fraction recorded a non-competitive mode of inhibition of α-glucosidase activity. The cytotoxicity exhibited against HELA cell was IC50 0.4 mg/ml and found positive in inhibiting the growth of Bacillus cereus, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa. Additionally, ensemble docking and molecular dynamic simulation showed that, out of the four PSMs examined, methyl 12,13-tetradecadienoate interacted with the α-glucosidase enzyme's allosteric site (BE −128.78 kJ/mol) and changed the configurations of the catalytic sites, as demonstrated by the enzyme's decreased affinity for isomaltose. The study found that PSMs from WC fruit may inhibit α-glucosidase, making them viable candidates for antidiabetic medication development.

Insights into the Peroxide-Bicyclic Intermediate Pathway of Aromatic Photooxidation: Experimental Yields and NOx-Dependency of Ring-Opening and Ring-Retaining Products.

Aromatic hydrocarbons are important contributors to the formation of ozone and secondary organic aerosols in urban environments. The different parallel pathways in aromatic oxidation, however, remain inadequately understood. Here, we investigated the production yields and chemical distributions of gas-phase tracer products during the photooxidation of alkylbenzenes at atmospheric OH levels with NOx present using high-resolution mass spectrometers. The peroxide-bicyclic intermediate pathway emerged as the major pathway in aromatic oxidation, accounting for 52.1 ± 12.6%, 66.1 ± 16.6%, and 81.4 ± 24.3% of the total OH oxidation of toluene, m-xylene, and 1,3,5-trimethylbenzene, respectively. Notably, the yields of bicyclic nitrates produced from the reactions of bicyclic peroxy radicals (BPRs) with NO were considerably lower (3-5 times) than what the current mechanism predicted. Alongside traditional ring-opening products formed through the bicyclic pathway (dicarbonyls and furanones), we identified a significant proportion of carbonyl olefinic acids generated via the 1,5-aldehydic H-shift occurring in subsequent reactions of BPRs + NO, contributing 4-7% of the carbon flow in aromatic oxidation. Moreover, the observed NOx-dependencies of ring-opening and ring-retaining product yields provide insights into the competitive nature of reactions involving BPRs with NO, HO2, and RO2, which determine the refined product distributions and offer an explanation for the discrepancies between the experimental and model-based results.

Non-peptide compounds from Kronopolites svenhedini (Verhoeff) and their antitumor and iNOS inhibitory activities.

Six new compounds, including a tetralone 1, two xanthones 2 and 3, a flavan derivative 4, and two nor-diterpenoids 7 and 8, accompanied by two known flavan derivatives 5 and 6 and a known olefine acid (9) were isolated from whole bodies of Kronopolites svenhedini (Verhoeff). The structures of the new compounds were determined by 1D and 2D nuclear magnetic resonance (NMR) and other spectroscopic methods, as well as computational methods. Selected compounds were evaluated for their biological properties against a mouse pancreatic cancer cell line and inhibitory effects on iNOS and COX-2 in RAW264.7 cells.

Thermal oxidation of model molecules to reveal vegetable oil polymerization studied by NMR spectroscopy and self‐diffusion

AbstractOxidative polymerization of plant oils and lipids is poorly understood yet widely encountered. Oils and fats are renewable resources providing biofuels and polymers. Oil oxidation is accelerated at high temperatures, typically above 110°C, where triacylglycerides are converted into toxic compounds and viscous deleterious polymers. Polymerization of mono‐unsaturated oil (210°C, 3 h, open to air) was investigated by comparing four similar sized molecules with different functional groups: oleic acid, methyl oleate, trans‐7‐tetradecene, and stearic acid. Non‐volatile products identified by NMR spectroscopy are minor ketones for saturated fatty acid (stearic acid), epoxides for acyl chains without acid groups (methyl oleate, tetradecane) and copious oligomerization, through ester cross‐links, for acyl chains with acid, and olefinic groups (oleic acid). Long range CH coupling clearly shows ester (not ether) cross‐links, contradicting long‐held beliefs. Chain fragmentation also occurs for heated oleic acid as revealed by formation of a species with a methylene group bonded to oxygen of an ester, CH2OC(O). Large size (slow diffusion) of the first oligomer (trimer) formed from oleic acid, used to represent hydrolyzed vegetable oil, was evidenced by DOSY (diffusion‐ordered spectroscopy). Combined NMR results show oligomers found in heated oleic acid are fatty acid estolides. Model oil reactions demonstrate why olefin and carboxylic acid groups are required for polymerization.

A Catalytic Asymmetric Hydrolactonization.

Despite recent advancements in the development of catalytic asymmetric electrophile induced lactonization reactions of olefinic carboxylic acids, the archetypical hydrolactonization has long remained an unsolved and well-recognized challenge. Here, we report the realization of a catalytic asymmetric hydrolactonization using a confined imidodiphosphorimidate (IDPi) Brønsted acid catalyst. The method is operationally simple, scalable, and compatible with a wide variety of substrates. Its potential is showcased with concise syntheses of the sesquiterpenes (-)-boivinianin A and (+)-gossonorol. Through in-depth physicochemical and DFT analyses, we derive a nuanced picture of the mechanism and enantioselectivity of this reaction.

Indane-Based Chiral Aryl Chalcogenide Catalysts: Development and Applications in Asymmetric Electrophilic Reactions.

Asymmetric electrophilic reactions provide an ideal method for the construction of chiral molecules by incorporating one or more functional groups into the parent substrates under mild conditions. However, due to the issues of the reactivities of electrophilic species and the possible racemization of chiral intermediates as well as the restriction of the chiral scaffolds of chiral catalysts, many limitations remain in this field, such as the narrow scopes of substrates and electrophiles as well as the limited types of nucleophiles and reactions. To overcome the limitations in the synthesis of diversified chiral molecules, we developed a series of indane-based chiral amino aryl chalcogenide catalysts. These catalysts are easily prepared based on the privileged chiral indane scaffold. They can provide an appropriate H-bonding effect by varying the amino protecting groups as well as offer a proper Lewis basicity and steric hindrance by adjusting different substituents on the aryl chalcogenide motifs. These features allow for them to meet the requirements of reactivity and the chiral environment of the reactions. Notably, they have been successfully applied to various asymmetric electrophilic reactions of alkenes, alkynes, and arenes, expanding the field of electrophilic reactions.Using these catalysts, we realized the enantioselective CF3S-lactonization of olefinic carboxylic acids, enantioselective CF3S-aminocyclization of olefinic sulfonamides, desymmetrizing enantioselective CF3S-carbocyclization of gem-diaryl-tethered alkenes, enantioselective CF3S-oxycyclization of N-allylamides, enantioselective intermolecular trifluoromethylthiolating difunctionalization and allylic C-H trifluoromethylthiolation of trisubstituted alkenes, formally the intermolecular CF3S-oxyfunctionalization of aliphatic internal alkenes, intermolecular azidothiolation, oxythiolation, thioarylation of N-allyl sulfonamides, desymmetrizing enantioselective chlorocarbocyclization of aryl-tethered diolefins, enantioselective Friedel-Crafts-type electrophilic chlorination of N-allyl anilides, and enantioselective chlorocarbocyclization and dearomatization of N-allyl 1-naphthanilides. Additionally, the enantioselective electrophilic carbothiolation of alkynes to construct enantiopure carbon chirality center-containing molecules and axially chiral amino sulfide vinyl arenes and the electrophilic aromatic halogenation to produce P-chirogenic compounds can be accomplished. In these reactions, a bifunctional binding mode is proposed in the catalytic cycles, in which an acid-derived anion-binding interaction might exist and account for the high enantioselectivities of the reactions.In this Account, we demonstrate our achievements in asymmetric electrophilic reactions and share our thoughts on catalyst design, our understanding of asymmetric electrophilic reactions, and our perspectives in the field of chiral chalcogenide-catalyzed asymmetric electrophilic reactions. We hope that the experience we share will promote the design and development of other novel organocatalysts and new challenging reactions.

Nickel-catalyzed hydroarylation reaction: a useful tool in organic synthesis

The nickel-catalyzed hydroarylation reaction opens up new routes to access complex organic compounds in a highly regio and stereoselective fashion from easily available precursors, such as olefin, alkyne, arene, aryl halide, and aryl boronic acid.

Dissipation of imidacloprid and its metabolites in Chinese prickly ash (Zanthoxylum) and their dietary risk assessment

Dissipation of imidacloprid (IMI) and its metabolites (urea, olefin, 5-hydroxy, guanidine, 6-chloronicotinic acid) in Chinese prickly ash (CPA) was investigated using QuEChERS combined with UPLC-MS/MS. Good linearity (r2 ≥0.9963), accuracy (recoveries of 71.8–104.3%), precision (relative standard deviations of 0.9–9.4%), and sensitivity (limit of quantification ≤0.05 mg kg−1) were obtained. After application of IMI at dosage of 467 mg a.i. L−1 for three times with interval of 7 d, the dissipation dynamics of IMI in CPA followed first-order kinetics, with half-life of 6.48–7.29 d. IMI was the main compound in CPA, followed by urea and guanidine with small amounts of olefin, 5-hydroxy, and 6-chloronicotinic acid. The terminal residues of total IMI and its metabolites at PHI of 14–21 d were 0.16–7.80 mg kg−1 in fresh CPA and 0.41–10.44 mg kg−1 in dried CPA, with the median processing factor of 3.62. Risk assessment showed the acute (RQa) and chronic dietary risk quotients (RQc) of IMI in CPA were 0.020–0.083% and 0.052–0.334%, respectively. Based on the dietary structures of different genders and ages of Chinese people, the whole dietary risk assessment indicated that RQc was less than 100% for the general population except for 2- to 7-year-old children (RQc of 109.9%), implying the long-term risks of IMI were acceptable to common consumers except for children.

A Catalyst-Controlled Enantiodivergent Bromolactonization.

A catalyst-controlled enantiodivergent bromolactonization of olefinic acids has been developed. Quinine-derived amino-amides bearing the same chiral core but different achiral aryl substituents were used as the catalysts. Switching the methoxy substituent in the aryl amide system from meta- to ortho-position results in a complete switch in asymmetric induction to afford the desired lactone in good enantioselectivity and yield. Mechanistic studies, including chemical experiments and density functional theory calculations, reveal that the differences in steric and electronic effects of the catalyst substituent alter the reaction mechanism.

Effects of Amorphous Poly Alpha Olefin (APAO) and Polyphosphoric Acid (PPA) on the Rheological Properties, Compatibility and Stability of Asphalt Binder

High production costs and poor storage stability have become important constraints in the manufacture of modified asphalt binder. To simplify the production process and reduce the production cost, amorphous poly alpha olefin (APAO) and polyphosphoric acid (PPA) were applied to prepare highly stable modified asphalt binder. The influence of APAO/PPA on the temperature sensitivity, rheological property, storage stability, compatibility and microstructure of neat binder were studied by rotational viscosity (RV), dynamic shear rheometer (DSR), bending beam rheometer (BBR) and Fourier transform infrared (FTIR) spectroscopy. The results show that the incorporation of APAO/PPA reduced the temperature sensitivity of neat binder. The combined effect of APAO/PPA contributed to the improvement in deformation resistance, which was evidenced by the increase in failure temperature and percent recovery. However, the compound modification of APAO/PPA decreased the binder’s low-temperature performance. APAO strengthened the fatigue resistance of the binder, while PPA reduced the anti-fatigue performance. Composite modified asphalt binder with superior storage stability could be prepared, which was confirmed by the desired Cole–Cole plots and fluorescence imaging. Furthermore, chemical and physical reactions occurred during the APAO/PPA modification process. Overall, 2 wt.% (weight percentage) APAO and 1.5 wt.% PPA are recommended for the production of modified asphalt binder with remarkable rheological performance and storage stability.

Site-selective and Stereoselective Syntheses Controlled by the Electron-withdrawing Properties of Cationic Heterocycles

This article describes our stereoselective and site-selective chemical methods for exploiting cationic heterocycles as electron-withdrawing groups (EWGs). We envisioned that the phosphoramide N-H proton of a pyridyl phosphoramide 3 would be activated by the cationic pyridinium moiety that is formed upon protonation. The resulting imide-like N-H proton and the acidic pyridinium proton of the pyridinium phosphoramide 3⋅HX cooperate together, making 3⋅HX a highly acidic dual Brønsted acid. The catalytic ability of 3⋅HX was demonstrated in the development of the first asymmetric Diels-Alder reaction between 1-amide dienes and maleimides. Focusing on the activation of N-bromosuccinimide (NBS) because of its structural similarity to maleimides, the enantioselective bromolactonization of trisubstituted olefinic acids was accomplished utilizing pyridyl phosphoramide 3f as a Brønsted base catalyst bearing an acidic N-H proton. Lastly, our strategy for the site-selective acylation of polyol compounds is described. In our system, a pyridine aldoxime ester 10, used as a mild acylating reagent, was activated by a catalytic amount of Lewis acid via the inductive effect of the cationic pyridinium moiety. The resulting metal complex preferentially attracted the alcohol with a Lewis basic site, thereby facilitating selective acylation via a template effect. This metal-template-driven strategy allowed for the site-selective acylation of diverse α-hydroxyamides, including unprotected N-glycolyl aminosugars.

A cascade approach to 3D cyclic carbamates via an ionic decarboxylative functionalization of olefinic oxamic acids.

An m-CPBA-mediated intramolecular epoxidation-decarboxylative alkoxylation cascade reaction of olefinic oxamic acids has been developed. The distinct ionic decarboxylative mechanism was preliminarily revealed. The protocol features mild reaction conditions and operational simplicity, allowing the construction of diverse medicinally valuable 5-7 membered 3D cyclic carbamate architectures in moderate to high yields.

Synthesis of seven-membered lactones by regioselective and stereoselective iodolactonization of electron-deficient olefins.

A regio- and stereoselective iodolactonization of internal electron-deficient olefinic acids has been reported, which provides a straightforward access to a series of multi-functionalized seven-membered lactones containing two consecutive chiral centers. The ester substituents on the olefins played a key role in achieving high regioselectivity. This result was proved through experiments and DFT calculations.

Co-metabolic enzymes and pathways of 3-phenoxybenzoic acid degradation by Aspergillus oryzae M-4.

As an intermediate metabolite of pyrethroids, 3-phenoxybenzoic acid (3-PBA) is more toxic than its parent compounds and has been detected in milk, soil, and human urine. 3-PBA can be metabolized through microbial degradation, but the microbial co-metabolic enzymes and pathways involved in 3-PBA degradation are unclear. This study investigated the enzymes types and possible pathways in the co-metabolic degradation of 3-PBA by Aspergillus oryzae M-4. The enzymes involved in co-metabolic degradation of 3-PBA and its intermediate metabolites were induced, and existed extracellularly and intracellularly except the catechol-degrading enzyme. Inhibitors and inducers of these oxidases were used to examine the enzymes required for co-metabolic degradation of 3-PBA and its intermediate metabolites. 3-PBA is hydroxylated to produce 3-hydroxy-5-phenoxy benzoic acid through the catalytic actions of lignin peroxidase (LiP). Phenol and gallic acid, the metabolites of 3-PBA, are produced via cleavage of an ether bond under the catalytic actions of cytochrome P450 (CYP450) and LiP. Phenol can be converted to catechol by LiP; catechol and gallic acid are cleaved to form long-chain olefin acid or olefin aldehyde by dioxygenase and LiP. In corn flour, some of these enzyme activators such as FeCl3, 4-cumaric acid, veratryl alcohol and sodium periodate appeared to improve 3-PBA degradation. The results provide a reliable pathway and characteristics for co-metabolic microbial degradation of 3-PBA in food and the environment.

Enantioselective Bromolactonization of Trisubstituted Olefinic Acids Catalyzed by Chiral Pyridyl Phosphoramides.

Enantioselective bromolactonization of trisubstituted olefinic acids producing synthetically useful chiral lactones with two contiguous asymmetric centers has remained mainly unexplored except for the 6-exo cyclization mode. In this work, the 5-exo- and 6-endo modes of bromocyclization of trisubstituted olefinic acids were enabled for the first time using N-bromosuccinimide and a pyridyl phosphoramide catalyst. The utility of the resulting bromolactones was demonstrated by transformations harnessing reactive alkyl bromide moieties without losing stereochemical information. Optimization studies and control experiments revealed that the basicity of pyridine moieties and presence of N-H protons in the phosphoramide species strongly affected both the reactivity and enantioselectivity parameters.

Metal-free synthesis of 1,2-amino alcohols by one-pot olefin aziridination and acid ring-opening

A one-pot, two-step reaction comprising olefin aziridination and ring-opening of an aziridine intermediate to synthesize 1,2-amino alcohols has been developed. This reaction is suitable for several types of olefin. This methodology allows an efficient and highly stereoselective approach to various 1,2-amino alcohols, readily providing an alternative route to conventional vicinal amino alcohols.

Total synthesis of Carpatamides A–D

A synthetic strategy was developed for the synthesis of the common core structure of Carpatamides A–D. The total synthesis of Carpatamides A and C was completed in 6 steps and of Carpatamides B and D in 7 steps, by employing the Wittig olefination, olefin cross metathesis and acid amine coupling reactions as key steps.

Enantioselective Bromolactonization of Deactivated Olefinic Acids.

A novel enantioselective bromolactonization of α,β-unsaturated ketones using bifunctional amino-urea catalysts has been developed. The scope of the reaction is evidenced by 23 examples of halolactones bearing various functionalities with up to 99% yield and 99:1 er. Unlike typical urea catalysts that require electron-deficient substituents to enhance the hydrogen bond strength, it is interesting to realize that electron-rich ureas are essential for high enantioselectivity in this case. Moreover, experimental data reveals that the halolactone compounds exhibit considerable anti-inflammatory effects on LPS-induced RAW 264.7 cells.

Enantioselective Halolactonization Reactions using BINOL-Derived Bifunctional Catalysts: Methodology, Diversification, and Applications.

A general protocol is described for inducing enantioselective halolactonizations of unsaturated carboxylic acids using novel bifunctional organic catalysts derived from a chiral binaphthalene scaffold. Bromo- and iodolactonization reactions of diversely substituted, unsaturated carboxylic acids proceed with high degrees of enantioselectivity, regioselectivity, and diastereoselectivity. Notably, these BINOL-derived catalysts are the first to induce the bromo- and iodolactonizations of 5-alkyl-4( Z)-olefinic acids via 5- exo mode cyclizations to give lactones in which new carbon-halogen bonds are created at a stereogenic center with high diastereo- and enantioselectivities. Iodolactonizations of 6-substituted-5( Z)-olefinic acids also occur via 6- exo cyclizations to provide δ-lactones with excellent enantioselectivities. Several notable applications of this halolactonization methodology were developed for desymmetrization, kinetic resolution, and epoxidation of Z-alkenes. The utility of these reactions is demonstrated by their application to a synthesis of precursors of the F-ring subunit of kibdelone C and to the shortest catalytic, enantioselective synthesis of (+)-disparlure reported to date.

Synthesis of (+)-Disparlure via Enantioselective Iodolactonization.

The BINOL-amidine organic catalyst 1 was previously shown to promote highly efficient enantioselective halolactonization reactions of olefinic acids. As part of these studies, it was discovered that the enantioenriched iodolactones could be easily converted into enantioenriched cis-1,2-disubstituted epoxides. This halolactonization-epoxidation sequence was applied to the synthesis of (+)-disparlure, which resulted in the shortest catalytic enantioselective synthesis to date, requiring only five steps and proceeding in 33% yield.