Maleopimaric Acid Research Articles

Synthesis of new 1,3-thiazol derivatives of maleopimaric acid as anticancer, antibacterial and antifungal agents

A series of new 1,3-thiazole derivatives of maleopimaric acid 6a–f, 7a–f were synthesized and evaluated for anticancer, antibacterial and antifungal activities. Evaluation of cytotoxic activity against human embryonic kidney 293 cells (HEK293), human neuroblastoma cell line (SH-SY5Y), hepatocellular carcinoma cell line (HepG2) and human T-cell lymphoblast-like line (Jurkat), showed that introduction of the aminothiazole fragment at position 6 of the diterpenoid molecule leads to decrease of cell viability. Substance 3 was found to be the most active against all tested cell lines, inhibiting cell viability with IC50 values in the range of 2–24 μM. The structure–activity relationship of these compounds was studied and the results show that the compounds 6c and 7e exhibited in vitro antifungal activity against Candida albicans and also possessed antibacterial profile against Enterobacter aerogenes, Klebsiella pneumoniae, Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli and Proteus vulgaris.

Rosin‐derived poly(vinyl chloride) plasticizer: Synthesis, structure, and properties

In this work, rosin‐based plasticizer was synthesized by Diels–Alder (DA) and esterification. First, the maleopimaric acid (RT) was obtained by DA between the double bond of rosin and maleic anhydride. Then, the carboxyl group and anhydride group of RT was esterified with tetrahydro geraniol to obtain the rosin‐based polyacid esters (RTT) under the catalysis of p‐toluene sulfonic acid. The structure of RT and RTT was detected by FTIR and 1H‐NMR. RTT was used as main plasticizer to obtain plasticized polyvinyl chloride (PVC) materials and compared with DOP. The results showed that RTT improved the thermal stability and reduced Tg of PVC film. Plasticized PVC films had excellent mechanical properties with the elastic modulus of −4,793.67 MPa and tensile strength of −111.86 MPa, higher than that of pure PVC and DOP‐6. RTT showed better volatility stability, migration, and solvent extraction in PVC compared to DOP. J. VINYL ADDIT. TECHNOL., 26:180–186, 2020. © 2019 Society of Plastics Engineers

Dual-functional antimicrobial coating based on a quaternary ammonium salt from rosin acid with in vitro and in vivo antimicrobial and antifouling properties

Bacterial colonization and biofilm formation on indwelling medical devices potentially cause serious and life-threatening infections. Technologies to prevent bacterial colonization and biofilm formation on biomedical devices are in great demand. Here, we report the preparation of coating monomers by conjugating rosin acid-derived maleopimaric acid quaternary ammonium cation (MPA-N+) with different chain of lengths allyloxy polyethylene glycol (APEG; either MW 1200 or 2400). The monomers of the cation plus its linker conjugates (APEG1200/2400-MPA-N+) were further grafted onto the surface of silicone rubber slides (PDMS) via plasma/UV-induced surface polymerization to form antimicrobial and antifouling coatings. The dual-functional coatings exhibited excellent antimicrobial activities against gram-negative and positive bacteria, and they effectively prevented biofilm formation. The coatings also greatly reduced protein adsorption and platelet adhesion, indicating their excellent antifouling capability. In addition, the APEG1200/2400-MPA-N+ cation coatings were biocompatible towards mammalian cells, as shown by in vitro cytotoxicity assays using rabbit erythrocytes and attached human aorta smooth muscle cells. In addition, the APEG2400-MPA-N+ coating exhibited significant anti-infective activity in a rodent subcutaneous infection model. We show that the APEG2400-MPA-N+ coating is an effective strategy for the prevention of infections associated with indwelling biomedical devices.

SYNTHESES OF POLYFLUOROALKYL ESTERS OF MALEOPIMARIC ACID N-PHENYLIMIDE

To meet the challenge of complex processing of plant material, in particular, tall oil rosin, research has been conducted on the synthesis of new polyfluroalkyl maleimides. As is well known, maleopimaric acid’s imides constitute a forward-looking class of organic compounds for pharmacology, agriculture, polymer chemistry and so on. The introduction of a fluorocarbon unit often gives high surface activity, chemical and heat resistance, hydrophobic and oleophobic properties. This paper presents the results of experiments on the synthesis of new N-phenylimides of maleopimaric acid’s polyfluoroalkyl esters by the interaction of the corresponding monosubstituted polyfluorinated maleopimarates with aniline during boiling for 10–16 h in toluene (40–52%). The starting N-phenylimide of maleopimaric acid has been obtained by two methods: by the Diels-Alder reaction from abietic acid and N-phenyl maleimide using sulfuric acid as a catalyst in the melt (40%) and by heating (MPA) with aniline in toluene (80%). 2,2,3,3,4,4,5,5-octafluoroamyl and 2,2,3,3,4,4,5,5,6,6,7,7,7- dodecaftaforpetyl ethers have been obtained by esterification of MPA with fluorinated alcohols under conditions of acid catalysis (70%). It have been identified the ester bonds are quite stable by TLC during long-term treatment of the stock (over 11 hours). The synthesized substances were analyzed with UV-, IR-, 1H NMR and 19F.

Nitrogen-Containing Heterocyclic Derivatives of Maleopimaric Acid by Carboxyl Function and their Antioxidant Activity

New N-heterocyclic maleopimaric acid derivatives were prepared and shown to affect free-radical oxidation in model systems, in particular, to suppress reactive oxygen species generation and stimulated lipid peroxidation in model systems containing lipoproteins.

Synthesis of N-Substituted Thiazacycloalkanes by Cyclothiomethylation of Primary Aliphatic Amines and Amino Derivatives of Maleopimaric Acid

Three-component cyclocondensation of primary aliphatic amines and amino derivatives of maleopimaric acid methyl ester with formaldehyde and carbochain (1,2-ethane-, 1,3-propane-, 1,4-butane-, 1,5-pentane-, 1,6-hexanedithiols) α,ω-dithiols or 3,6-dioxa-1,8-octanedithiol produced N-substituted thiazacycloalkanes.

Thermal behaviour and fungi resistance of composites based on wood and natural and synthetic epoxy resins cured with maleopimaric acid

Wood/epoxy resin composites based on diglycidyl ether of bisphenol A (DGEBA)/epoxidized oil (EO)/Diels–Alder adducts of resin acids with maleic anhydride (RAMA) in acetone (80%) were obtained by impregnation. Epoxidation was carried out in the presence of hydrogen peroxide (H2O2), acetic acid (AAc), sulfuric acid (H2SO4) as catalyst and cyclohexane (CHx) as solvent at a molar ratio of 0.5/1.5/1 (AAc/hydrogen peroxide/ethylene unsaturation). The kinetic parameters (activation energy and pre–exponential factor) of the DGEBA/EO/RAMA curing reaction and thermal characterization of the crosslinked compounds and wood epoxy composites (WECs) were obtained using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Based on the chemical structure of the evolved gases resulted during thermal decomposition of the crosslinked polymers and WECs, identified with FT–IR, a probable mechanism of thermal degradation was proposed. Resistance to three fungi was also tested.

Synthesis of the Conjugate of Maleopimaric Acid and Metronidazole

Synthesis of the Conjugate of Maleopimaric Acid and Metronidazole

CO2-Responsive Pickering Emulsions Stabilized by a Bio-based Rigid Surfactant with Nanosilica.

A novel CO2-responsive surfactant, maleopimaric acid glycidyl methacrylate ester 3-(dimethylamino)propylamine imide (MPAGN), based on sustainable resource of rosin was synthesized and used to prepare a kind of CO2-responsive Pickering emulsions with nanosilica. MPAGN can be reversibly responsive to CO2 and N2 between active cationic (MPAGNH+) and inactive nonionic (MPAGN), leading to adsorb on or desorb from the surface of nanosilica, then stabilize or break emulsion. CO2-responsive behavior of MPAGN was verified by cycle change of pH and conductivity with bubbling CO2 and N2 alternately. The type of adsorption of MPAGNH+ at the particle-water interface was explained according to the adsorption isotherms. The mechanisms of stabilization, destabilization, and restabilization of Pickering emulsion were analyzed according to zeta potentials and droplet size. This Pickering emulsion can be reversible between stable and unstable by bubbling CO2 and N2 alternately. Moreover, this emulsifier can be recycled when new oil was added after removing the initial oil. Therefore, it not only has economic benefits but also has an environmentally friendly property.

Synthesis and Biological Activity of Nitrilic Derivatives of the Methyl Ester of Maleopimaric Acid

An effective method of a modification of the anhydride ring of the maleopimaric acid methyl ester by means of the cyanoethylation reaction was developed. A primary screening of a cytotoxic activity in vitro demonstrated an ability of the cyanoethyl derivative of the maleopimaric acid methyl ester to induce the death of the PC-3 cells of prostate cancer.

Synthesis of 4,5-dihydroisoxazole derivatives of maleopimaric acid by 1,3-dipolar cycloaddition reaction between its allyl derivatives and aromatic nitrile oxides

While searching for pharmacologically active compounds among 4,5-dihydrooxazole derivatives of maleopimaric acid, we studied for the first time the reaction between allyl-substituted maleopimaric acid derivatives and aromatic nitrile oxides that were generated from oximes by oxidation with sodium hypochlorite with or without ultrasonication of the biphasic system. The reaction occurred under mild conditions and regiospecifically provided 4,5-dihydroisoxazol-5-ylmethyl derivatives of maleopimaric acid in 77–99% yields.

Interaction of allyl esters of alcohols-telomeres (n = 1, 2, 3) with maleopimaric acid

Interaction of allyl esters of alcohols-telomeres (n = 1, 2, 3) with maleopimaric acid

Use of Hempseed-Oil-Derived Polyacid and Rosin-Derived Anhydride Acid as Cocuring Agents for Epoxy Materials

A poly(carboxylic acid) [hempseed oil (HO)-polyacid] was prepared from the fatty acids of hempseed oil and used as a curing agent for epoxies. Polyunsaturated fatty acid (C18:2 and C18:3) that composed ∼77% of the hempseed oil fatty acid (HOFA) were introduced more carboxylic groups by conjugation followed by Diels–Alder addition with maleic anhydride and hydrolysis. This conversion process was further confirmed using pure methyl linolenate as a model compound. In addition, a rosin-derived anhydride acid, maleopimaric acid (MPA) that has a rigid molecular structure, was used as a cocuring agent. Effects of the HO-polyacid/MPA cocuring agents in different ratios on the curing behavior, dynamic mechanical properties, thermal stability, and flexural properties of a commercial bisphenol A epoxy were studied. The results suggest the balance of stiffness/flexibility of the cured resins was effectively regulated by varying the cocuring agent ratio.

New Amides and Imidoamides of Maleopimaric Acid as a Chiral Dopants for Nematic Liquid Crystal Compositions

A method for the synthesis of N-(4-alkyl, alkoxyphenyl)amides and imidoamides of maleopimaric acid was developed. Their thermal stability and optical activity were estimated. The properties of liquid crystal compositions with the synthesized compounds as chiral dopants were studied.

One-pot synthesis of 1,2,3-triazole derivatives of maleopimaric and dihydroquinopimaric acids

Effective one-pot synthesis of 1,2,3-triazole derivatives of maleopimaric and dihydroquinopimaric acids consists in the reaction of diterpene propargyl esters with organic azides generated in situ in the presence of СuI catalyst.

Curing kinetics and mechanical properties of bio-based composite using rosin-sourced anhydrides as curing agent for hot-melt prepreg

In this study, a novel bio-based thermosetting system has been developed from epoxy resin (EP), with rosin-sourced anhydrides (maleopimaric acid, RAM) as curing agent and imidazole type latent catalyst (two amino imidazole salt complex, IMA), to be used as matrix for hot-melt prepreg curing at mid-temperature. For comparison, the epoxy resin system with petroleum sourced hardener methylhexahydrophthalicanhydride (MHHPA) was also examined. The curing behaviour and mechanism were investigated by non-isothermal differential scanning calorimeter (DSC) analysis and Fourier transform infrared (FTIR) spectra. The results showed that the curing course of bio-based epoxy resin system containing RAM included two stages, which were the reaction between the free carboxyl group of RAM and oxirane ring under the acceleration of IMA, and the main reaction attributed to the reaction between anhydride and oxirane. According to Kissinger method, the reaction activation energy ( E a ) of two stages were 68.9 and 86.5 kJ mol‒1 , respectively. The E a of EP/MHHPA and EP/IMA resin system were 81.04 and 77.9 kJ mol‒1 . The processing property of EP/RAM/IMA system, i.e. the relationship between viscosity-temperature-time, was characterized by cone-plate viscometer aim to decide the processing parameter of prepreg preparation. The effect of RAM content on mechanical performance and dynamic mechanical property was investigated. Noteworthily, compared with the laminates with EP/MHHPA as matrix, the laminates with RAM as hardeners achieved a 44%, 73% and 70°C increase in bending strength, bending modulus and the glass transition temperature, respectively, due to the bulky hydrogenated phenanthrene ring structure incorporated into the cross-linking networks. When the fiber volume fraction reached 47%, the mechanical property of the laminates prepared with hot melt prepreg was superior or comparable to that of composites with pure petroleum sourced matrix. RAM as cross-linking agent of epoxy resin holds a great potential to satisfy the requirement of composites such as structure and secondary structure parts preparation.

Synthesis and antimicrobial activity of quinopimaric and maleopimaric acids

A number of nitrogen-, bromine-, and sulfur-containing derivatives of diene adducts of levopimaric acid have been synthesized. The testing of the compounds on Staphylococcus aureus and Klebsiella pneumoniae bacteria has shown that the compounds possess a weak antimicrobial activity.

New bio-based polymeric thermosets synthesized by ring-opening polymerization of epoxidized soybean oil with a green curing agent

New polymeric thermosets with a high bio-based content were obtained by the ring-opening polymerization of two biomass derivatives, epoxidized soybean oil and maleopimaric acid, catalysed by 2-ethyl-4-methylimidazole. Maleopimaric acid with a rigid hydrogenated phenanthrene ring structure was successfully synthesized in a large quantity from abietic acid and maleic anhydride using p-toluene sulfonic acid as a catalyst, by adapting and optimizing an industrial strategy. The advantages of using maleopimaric acid as a curing agent for epoxidized soybean oil, compared with its petroleum-based analogues, were studied in detail. The results showed that the total heat release for the ring-opening polymerization of epoxidized soybean oil and maleopimaric acid was only 31.7kJ/mol epoxy group. The tensile properties and glass transition temperature of the thermosets cured by maleopimaric acid were close to those of the products cured by the analogue with a cycloaliphatic ring, while the breaking elongation and storage modulus at room temperature of the former were greatly larger, exhibiting values of 61.5% and 1268MPa, respectively. Additionally, the products cured with maleopimaric acid had the best thermal stability with a 10%-weight-loss temperature up to 349°C and satisfactory chemical and water resistance.

Curing kinetics of bio‐based epoxy resin based on epoxidized soybean oil and green curing agent

New thermoset with a high bio‐based content was synthesized by curing epoxidized soybean oil (ESO) with a green curing agent maleopimaric acid catalyzed by 2‐ethly‐4‐methylimidazole. Non‐isothermal differential scanning calorimetry and a relatively new integral isoconversional method were used to analyze the curing kinetic behaviors and determine the activation energy (Ea). The two‐parameter Šesták–Berggren autocatalytic model was applied in the mathematical modeling to obtain the reaction orders and the pro‐exponential factor. For anhydride/epoxy group molar ratio equal to 0.7, Ea decreased from 82.70 to 80.17 kJ/mol when increasing the amount of catalyst from 0.5 to 1.5 phr toward ESO. The reaction orders m and n were 0.4148 and 1.109, respectively. The predicted non‐isothermal curing rates of Šesták–Berggren model matched perfectly with the experimental data. © 2016 American Institute of Chemical Engineers AIChE J, 63: 147–153, 2017

Synthesis and Pharmacological Evaluation of Maleopimaric N-arylimides: Identification of Novel Proapoptotic Agents.

Several N-aryl maleopimaric acid diimides (3a-3d, 4a-4g) were synthesized and evaluated their topoisomerase I inhibitory activities along with cytotoxicities against NCI, MGC-803, Bel-7404 and Hct-116 cell lines. The pharmacological dates revealed that most of structure analogs exhibited moderate to high levels of anticancer activities against the tested cancer cell lines. Compound 4g with phenylalanine substituent exhibited significant cytotoxicity against MGC-803 and Hct-116 cells (IC50 was 9.85±1.24 and 8.47±0.95 µM, respectively). All the synthesized compounds exhibited no cytotoxicity against HUVEC cells. In addition, maleopimaric diimides showed stronger cytotoxicity and topoisomerase I inhibitory activity compared to that of maleopimaric acid. Structure-activity relationship study showed that carboxyl and diimide moieties were important to display Topo I inhibitory activities. Further experiments proved that 4g could induce apoptosis of MGC-803 cells. In addition, the further mechanisms of compound 4g-induced apoptosis in MGC-803 cells demonstrated that compound 4g induced the activations of caspase-4, caspase-8 and caspase-3 for causing cell apoptosis, and altered antiand pro-apoptotic proteins. Moreover, cell cycle analysis indicated that the derivative 4g mainly arrested MGC-803 cells in S stage.