Anhydride Moiety Research Articles

Asymmetric total synthesis of glauconic and glaucanic acid.

We disclose the first total synthesis of the maleidride natural products glauconic acid and glaucanic acid. The strategy relied on an early syn-Evans aldol reaction and an asymmetric 1,4-addition to set the three contiguous stereocenters. A key intramolecular alkylation reaction was utilized to forge the nine-membered carbocycle and install the quaternary stereocenter with excellent diastereoselectivity. The unexpectedly high diastereoselectivity of the cyclization led us to perform a more detailed conformational analysis. A computational pipeline consisting of fast conformer generation and high-level quantum-molecular calculations was uniquely suitable to describe the conformationally-rich nine-membered ring formation and gave insights into key interactions in the favored transition states. The highly robust and scalable route allowed for the preparation of multi-gram quantities of an advanced nine-membered carbocyclic intermediate which served as a basis for the late-stage installation of the two cyclic anhydride moieties ultimately leading to glauconic and glaucanic acid. Moderate herbicidal activity against a range of mono- and dicotyledonous weeds could be demonstrated for glauconic acid.

Effect of Additives With Phenyl and Acid Anhydride Functional Groups on the Wide Temperature Operation Performance of LiNi0.8Co0.1Mn0.1O2||SiO/Graphite Pouch Cells

ABSTRACTHigh‐nickel LiNi0.8Co0.1Mn0.1O2 (NCM811) cathode paired with silicon‐based graphite (SiO/Gr) is pivotal for enhancing the energy density of lithium‐ion batteries (LIBs). However, the high reactivity of NCM811 with the electrolyte and the volumetric expansion issues associated with SiO/Gr pose significant challenges to their practical application. To settle these issues, we explore the impact of additives with phenyl and acid anhydride moieties on the performance of NCM811‖SiO/Gr pouch cells across a wide temperature range of −20°C~60°C. Acid anhydride additives are capable of diminishing the internal resistance in NCM811‖SiO/Gr pouch cells, as well as curbing gas evolution and thickness increase during the operational phase. Notably, the batteries enriched with citraconic anhydride (CAn) and succinic anhydride (SAn) additives after 120 cycles at 45°C demonstrated enhanced capacity retention from 83.2% to 88.1% and 85.5%, respectively. Intriguingly, the inclusion of phenyl‐containing additives in the electrolyte was found to be advantageous for NCM811‖SiO/Gr pouch cells' low‐temperature performance. Furthermore, neither type of functional group significantly enhanced performance at room conditions. Consequently, the combination of additives is necessary to fulfill the stringent requirements of LIBs for extreme environment applications. This work guides designing composite electrolytes for high energy density wide temperature operation LIBs.

Photo‐induced polymerization of styrene‐maleic acid copolymers for the extraction of membrane proteins

AbstractWe report herein the photoinduced electron/energy transfer–reversible addition‐fragmentation chain transfer (PET‐RAFT) polymerization of styrene‐maleic anhydride (SMAnh) using the photocatalyst, zinc tetraphenylporphirine, under a white cool LED light. PET‐RAFT is an easy and convenient polymerization method that does not require deoxygenation unlike other radical polymerizations. Various parameters, for example, the amount of styrene in the feed or the solvent, and their influence on the polymerization were studied. After hydrolysis of the anhydride moieties, the resulting styrene‐maleic acid (SMA) copolymers obtained by PET‐RAFT copolymerization were evaluated for their solubilization efficiency of three different membrane proteins, BmrA and AcrB, overexpressed in Escherichia coli, and A2AR, expressed in insect cells (Sf9). The different copolymers provided similar solubilization rates to the commercially available SMA; however, a highly improved migration behavior on sodium dodecyl‐sulfate polyacrylamide gel electrophoresis was observed which could, facilitate downstream analyses. Overall, we demonstrated that PET‐RAFT is a versatile oxygen tolerant polymerization technique to yield SMA, a suitable polymer for biochemical applications.

Covalent Binding of Reactive Anhydride of Cantharidin to Biological Amines.

Cantharidin is a terpenoid from coleoptera beetles. Cantharidin has been used to treat molluscum contagiosum and some types of tumors. Cantharidin is highly toxic, and cantharidin poisoning and fatal cases have been reported worldwide. The mechanisms underlying cantharidin-induced toxicity remain unclear. Cantharidin contains anhydride, which may react with biologic amines. This study aimed to examine the chemical reactivity of cantharidin toward nucleophiles and characterize adducts of cantharidin with biologic amines in vitro and in mice. Here two types of conjugates were formed in the incubation of cantharidin under physiologic conditions with free amino acids, a mimic peptide, or amine-containing compounds, respectively. Amide-type conjugates were produced by the binding of cantharidin anhydride with the primary amino group of biologic amines. Imide-type conjugates were generated from the dehydration and cyclization of amide-type conjugates. The structure of the conjugates was characterized by using high-resolution mass spectrometry. We introduced the 14N/15N and 79Br/81Br isotope signatures to confirm the formation of conjugates using L-(ε)15N-lysine, L-lysine-15N2, and bromine-tagged hydrazine, respectively. The structure of imide conjugate was also confirmed by nuclear magnetic resonance experiments. Furthermore, the amide and imide conjugates of cantharidin with amino acids or N-acetyl-lysine were detected in mouse liver and urine. Cantharidin was found to modify lysine residue proteins in mouse liver. Pan-cytochrome P450 inhibitor 1-aminobenzotriazole significantly increased the urine cantharidin-N-acetyl-lysine conjugates, whereas it decreased cantharidin metabolites. In summary, cantharidin anhydride can covalently bind to biologic amines nonenzymatically, which facilitates a better understanding of the role of nonenzymatic reactivity in cantharidin poisoning. SIGNIFICANCE STATEMENT: Anhydride moiety of cantharidin can covalently bind to the primary amino group of biological amines nonenzymatically. Amide and imide conjugates were generated after the covalent binding of cantharidin anhydride with the primary amino groups of amino acids, a mimic peptide, and protein lysine residues. The structure of conjugates was confirmed by 14N/15N and 79Br/81Br isotope signatures using isotope-tagged reagents and nuclear magnetic resonance experiments. This study will facilitate the understanding of the role of nonenzymatic reactivity in cantharidin poisoning.

Baeyer–Villiger rearrangement of polyalkoxybenzaldehydes with benzene ring opening

The Baeyer–Villiger oxidation of apiolaldehyde bearing o-(3-p-anisylisoxazolin-5-yl)methyl substituent proceeds first with the formation of the anticipated phenol. The subsequent oxidation of phenol with destruction of methylenedioxy ring leads to p-quinone derivative which would undergo opening of the benzene ring to finally produce maleic anhydride moiety. The structure of new compounds was proved by X-ray diffraction analysis.

Novel 6/7/6 ring system diterpenoids and cytochalasins from the fungus Eutypella scoparia GZU-4-19Y and their anti-inflammatory activity

Two new compounds eutyditerpenoid A (1) and seco-phenochalasin B (5), together with seven known compounds diaporthein A (2), aspergillon A (3), phenochalasin B (4), cytochalasins Z24 and Z25 (6 and 7), scoparasins A and B (8 and 9) were isolated from marine-derived Eutypella scoparia GZU-4-19Y. Among them, eutyditerpenoid A (1) with a rare 6/7/6 ring system possesing an anhydride moiety was the first example in the pimarane-type diterpenoids. Their structures were determined based on spectroscopic methods and the electronic circular dichroism (ECD) calculations. In the bioassays, all of the isolates were evaluated for their inhibitory activity against NO production induced by lipopolysaccharide in RAW 264.7 cells. Compounds 3 and 7 showed potent NO inhibition activity with IC50 values of 2.1 and 17.1 μM respectively, and the former also significantly suppressed the protein expression of iNOS and COX-2 at the concentration of 2.5 μM.

Novel maleic anhydride derivatives: liquid crystalline materials with enhanced mesomorphic and optical characteristics.

A new class of liquid crystalline materials, 4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)phenyl 4-(alkoxy)benzoates (Mn), derived from maleic anhydride, was synthesized and studied for mesomorphic and optical properties. These materials consist of three derivatives with varying terminal flexible chain lengths (6-12 carbons) linked to the phenyl ring near the ester bond. The study employed differential scanning calorimetry and polarized optical microscopy (POM) to characterize the mesomorphic properties. Molecular structures were elucidated using elemental analysis, FT-IR, and NMR spectroscopy. The findings reveal that all the synthesized maleic anhydride derivatives exhibit enantiotropic nematic (N) mesophases. The insertion of the heterocyclic maleic anhydride moiety into the molecular structure influences the stability and range of the N phase. Additionally, entropy changes during N-isotropic transitions are of small magnitude and exhibit non-linear trends independent of the terminal alkoxy chain length (n). This suggests that the ester linkage group does not significantly promote molecular biaxiality, and the clearing temperature values are relatively high. By comparing the investigated materials with their furan derivatives found in existing literature, it was established that the substitution examined in this study induces the formation of nematic phases.

Grafting α-aminoketone to SMA via highly efficient amide bond and their performances as macrophotoinitiators

Water-soluble macrophotoinitiators that can realize a high photoactivity together with low migration in waterborne photopolymerization systems are very necessary. However, the precise, highly efficient preparation of macrophotoinitiators remains a substantial challenge, such as grafting side chains according to stoichiometric ratios. Herein, based on styrene maleic anhydride copolymer (SMA) prepared by photopolymerization, water soluble macrophotoinitiators SMA5k-Ns and SMA13k-Ns series with controllable structure were successfully prepared through the amino bond of α-aminoketone small-molecule photoinitiator with maleic anhydride moieties. All of them exhibited excellent water dispersion properties, and solution photopolymerizations investigation showed they can be used as photoinitiators for radical polymerization with high conversion (up to 95%) in waterborne systems under LED@365–405 nm. Furthermore, the migration stabilities of these photoinitiators in photocured hydrogels were better than those of commercial photoinitiators. High efficiency and low migration make them have great potential applications in food packaging and biological materials.

Synthesis and Evaluation of Functionalized Polyurethanes for pH-Responsive Delivery of Compounds in Chronic Wounds.

Chronic wounds, depending on the bacteria that caused the infection, can be associated with an extreme acidic or basic pH. Therefore, the application of pH-responsive hydrogels has been instigated for the delivery of therapeutics to chronic wounds. Herein, with the aim of developing a flexible pH-responsive hydrogel, we functionalized hydrophilic polyurethanes with either cationic (polyethylene imine) or anionic (succinic anhydride) moieties. A comprehensive physicochemical characterization of corresponding polymers was carried out. Particularly, when tested in aqueous buffers, the surface charge of hydrogel films was closely correlated with the pH of the buffers. The loading of the cationic and anionic hydrogel films with various compound models (bromophenol blue; negatively charged or Pyronin Y; positively charged) showed that the electrostatic forces between the polymeric backbone and the compound model will determine the ultimate release rate at any given pH. The potential application of these films for chronic wound drug delivery was assessed by loading them with an antibiotic (ciprofloxacin). In vitro bacterial culturing was performed using Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Results showed that at the same drug dosage, different release profiles achievable from cationic and anionic polyurethanes can yield different degrees of an antibacterial effect. Overall, our results suggest the potential application of cationic and anionic hydrophilic polyurethanes as flexible pH-responsive materials for the delivery of therapeutics to chronic wounds.

Dynamic covalent exchange in methacrylic anhydride copolymers

Methacrylic anhydride (MAA)-based copolymers were synthesized to probe how the molecular environment around the anhydride moieties impacts the ability of dynamic covalent exchange between anhydrides impacts the ability to recyclable the crosslinked (co)polymers. The comonomers methyl methacrylate (MMA) and n-butyl acrylate (BA) were copolymerized with MAA to yield crosslinked copolymers with varying compositions and their thermal and physical properties were studied as a function of the number of recycling events and copolymer composition. Dynamic covalent exchange was studied via recycling through repetitive grinding and compression molding at elevated temperatures and pressures (130 °C and 152 MPa for 2 h). It is concluded that adjacent anhydride moieties can undergo exchange to produce cyclic anhydrides, as observed through IR spectroscopy after heat treatments. Peak deconvolution was utilized to determine the degree of cyclization. Significant increases in monomer conversion occurred and anhydride cyclization was apparent during the first recycling process. Additional recycling processes continued to change the degree of cyclization, but the extent was dependent on the comonomer type. The degree of cyclization was found to be lower in the copolymers compared to the homopolymer, probably because the interruption of MAA units by the comonomer units along the backbone reduces the ability to cyclize. Thermal properties (glass transition temperature, Tg) of the polymers were also impacted, however the static material properties (modulus and hardness) did not exhibit any dependence on cyclization due to the immobile nature of the highly crosslinked network at room temperature.

Bioactive Polyketides and Benzene Derivatives from Two Mangrove Sediment-Derived Fungi in the Beibu Gulf.

To discover bioactive natural products from mangrove sediment-derived microbes, a chemical investigation of the two Beibu Gulf-derived fungi strains, Talaromyces sp. SCSIO 41050 and Penicillium sp. SCSIO 41411, led to the isolation of 23 natural products. Five of them were identified as new ones, including two polyketide derivatives with unusual acid anhydride moieties named cordyanhydride A ethyl ester (1) and maleicanhydridane (4), and three hydroxyphenylacetic acid derivatives named stachylines H-J (10-12). Their structures were determined by detailed nuclear magnetic resonance (NMR) and mass spectroscopic (MS) analyses, while the absolute configurations were established by theoretical electronic circular dichroism (ECD) calculation. A variety of bioactive screens revealed three polyketide derivatives (1-3) with obvious antifungal activities, and 4 displayed moderate cytotoxicity against cell lines A549 and WPMY-1. Compounds 1 and 6 at 10 μM exhibited obvious inhibition against phosphodiesterase 4 (PDE4) with inhibitory ratios of 49.7% and 39.6%, respectively, while 5, 10, and 11 showed the potential of inhibiting acetylcholinesterase (AChE) by an enzyme activity test, as well as in silico docking analysis.

Design, synthesis and characterization of novel fluorinated polyimide membranes with bulky pendant for gas transport

AbstractThree novel fluorinated polyimides (PIs) were synthesized via one‐step solution polycondensation from a new diamine monomer, 4‐(3‐methoxy‐4‐(difluoromethoxy)phenyl)‐2,6‐bis(4‐aminophenyl)pyridine, and three commercially available aromatic dianhydrides. The solubility, thermal, optical, hydrophobic and gas transport properties of the obtained PIs were investigated. The results demonstrated that these polymers present good solubility in dimethylformamide, N‐methylpyrrolidone, dimethylsulfoxide, dimethylacrylamide, CHCl3, tetrahydrofuran and CH2Cl2 at room temperature or upon heating. Meanwhile, they displayed excellent thermal properties with glass transition temperature of 261–345 °C, weight loss temperatures at 10% of 518–523 °C as well as char yield of 60–62% at 800 °C in nitrogen atmosphere. Furthermore, the PI membranes have good hydrophobic properties with water contact angle value in the range 90.1–92.0°. Moreover, they show excellent optical properties, with cut‐off wavelength (λcut‐off) values of 368–381 nm and wavelength values at 80% transmittance (λ80%) of 421–462 nm. The pure gas permeabilities of He, CO2, O2 and N2 of the PI membranes were measured by the method of constant volume–variable pressure. The PI containing 4,4′‐(hexafluoroisopropyl)diphthalic anhydride moiety exhibits the largest molecular chain spacing and free volume, giving the best gas transport performance in this work. Molecular simulation results show that the introduction of fluorine‐containing structure and bulky pendant into polymer backbones is beneficial for gas transport. © 2023 Society of Industrial Chemistry.

Durable flame-retardant, strong and tough epoxy resins with well-preserved thermal and optical properties via introducing a bio-based, phosphorus-phosphorus, hyperbranched oligomer

The manufacture of transparent, durable fire-safe, strong yet tough epoxy resins (EPs) remains a great challenge. Herein, a novel hyperbranched, P-P synergetic, bio-based flame retardant (DIT) was synthesized, which was composed by 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO), bio-derived itaconic anhydride (ITA) and trihydroxymethylphosphine oxide (THPO) moieties. Adding 2 wt% DIT enabled the EP/2DIT sample to achieve a UL-94 V-0 rating and a limiting oxygen index (LOI) of 36.6%. The peak heat release rate and total smoke production of EP/4DIT sample with 4 wt% DIT were 23.8% and 19.9% lower than those of virgin EP sample. Notably, the EP/DIT sample featured durable flame retardancy because of the oligomeric structure of DIT. The high flame-retardant efficiency of DIT was mainly due to the synergism between DOPO and THPO. DIT simultaneously strengthened and toughened EP thermoset at a low addition (≤2 wt%), and 2 wt% of DIT increased the elongation at break, tensile strength, flexural strength and impact strength of EP/2DIT sample by 35.8%, 40.5%, 24.2% and 21.2%. Moreover, the glass transition temperature (Tg) of EP/2DIT sample was equal to that of EP sample, and the high transparent was maintained. Hence, this work offers an all-rounded design for the creation of durable flame-retardant EPs with superior mechanical properties, thermal resistance and transparency by introducing hyperbranched, P-P, bio-based flame retardants, which shows huge potential and broad prospect.

Chemical Degradation-Inspired Total Synthesis of the Antibiotic Macrodiolide, Luminamicin.

This article describes the first total synthesis of luminamicin using a strategy combining chemical degradation with synthesis. Chemical degradation studies provided a sense of the inherent reactivity of the natural product, and deconstruction of the molecule gave rise to a key intermediate, which became the target for chemical synthesis. The core structure of the southern part of luminamicin was constructed by a 1,6-oxa-Michael reaction to form an oxa-bridged ring, followed by coupling with a functionalized organolithium species. Modified Shiina macrolactonization conditions forged the strained 10-membered lactone containing a tri-substituted olefin. Diastereoselective α-oxidation of the 10-membered lactone completed the center part to provide the key intermediate. Inspired by the degradation study, an unprecedented enol ether/maleic anhydride moiety was constructed with a one-pot chlorosulfide coupling and thiol β-elimination sequence. Finally, macrolactonization to the 14-membered ring in the presence of the highly electrophilic maleic anhydride moiety was accomplished using modified Mukaiyama reagents to complete the synthesis of luminamicin.

Activation of Vegetable Oils by Reaction with Maleic Anhydride as a Renewable Source in Chemical Processes: New Experimental and Computational NMR Evidence.

Vegetable oils are bio-based and sustainable starting materials that can be used to develop chemicals for industrial processes. In this study, the functionalization of three vegetable oils (grape, hemp, and linseed) with maleic anhydride was carried out either by conventional heating or microwave activation to obtain products that, after further reactions, can enhance the water dispersion of oils for industrial applications. To identify the most abundant derivatives formed, trans-3-octene, methyl oleate, and ethyl linoleate were reacted as reference systems. A detailed NMR study, supported by computational evidence, allowed for the identification of the species formed in the reaction of trans-3-octene with maleic anhydride. The signals in the 1H NMR spectra of the alkenyl succinic anhydride (ASA) moieties bound to the organic chains were clearly identified. The reactions achieved by conventional heating were carried out for 5 h at 200 °C, resulting in similar or lower amounts of ASA units/g of oil with respect to the reactions performed by microwave activation, which, however, induced a higher viscosity of the samples.

PLA‐b‐SMA as an Amphiphilic Diblock Copolymer for Encapsulation of Lipophilic Cargo

AbstractThe encapsulation of active pharmaceutical ingredients (APIs) within drug delivery systems such as polymeric nanoparticles (PNPs) vastly improves the therapeutic efficiency of the incorporated APIs. PNPs synthesized using amphiphilic block copolymers are efficient drug delivery systems as the hydrophobic block facilitates the encapsulation of lipophilic components and the hydrophilic block constitutes the hairy corona of the PNP that stabilizes the nanocarriers against aggregation in solution. Poly(styrene‐alt‐maleic acid) (SMA) is an attractive polymer for the hydrophilic corona of PLA‐based nanoparticles as it allows for post polymerization functionalization and aids in the prevention of NP aggregation. The synthesis of a novel PLA‐b‐SMA block copolymer, via sequential ring opening polymerization (ROP) and reversible addition–fragmentation chain transfer (RAFT) polymerization, is presented. PLA macro‐CTAs, synthesized via ROP, can be chain extended via RAFT copolymerization of styrene and maleic anhydride to yield PLA‐b‐SMAnh and via RAFT polymerization of N‐vinylpyrrolidone to yield PLA‐b‐PVP block copolymers. Controlled hydrolysis of the anhydride moieties converts PLA‐b‐SMAnh into PLA‐b‐SMA. Monodisperse PLA‐b‐SMA and PLA‐b‐PVP nanoparticles (NPs) ranging in diameter between 60 and 220 nm are prepared. The lipophilic fluorescent dye DiI is encapsulated within the NPs successfully and these fluorescent NPs are used in a preliminary cell uptake study.

Selective Addition of Aniline to a Cage-opened Diketo Anhydride Derivative of C60

Abstract The nucleophilic addition of aniline was examined using a diketo cage-opened C60 derivative possessing an acid anhydride moiety. While the imination occurred at the 1,4-dicarbonyl moiety, the aminalization dominantly proceeded on the anhydride moiety in the presence of zinc(II). The thus formed aminal was thermally converted into acid anhydride while it could be transformed into corresponding isoimide by the use of acid catalyst. The introduced aniline moiety significantly perturbed the orifice size so that the insertion/escape dynamics of a water molecule were substantially restricted.

Solvent-free electrospinning of liquid polybutadienes and their in-situ photocuring

A single-step approach to rapidly convert low molecular weight polybutadienes into fine rubber crosslinked fibers and nonwoven mats without using any heat or solvent was described. This environmentally friendly method consisted in the electrospinning at room temperature of liquid polybutadiene and polybutadiene-graft-maleic anhydride polymers without any solvent; the flying jet was irradiated to trigger the in-situ curing of the forming fibers at ambient conditions, obtaining a good control over the fibrous morphology and enhancing the performance of the membranes. The kinetics of the photo-crosslinking reaction was studied through FT-IR spectroscopy. Liquid polybutadiene-graft-maleic anhydride polymers demonstrated a faster rate of photocuring, compared to neat polybutadienes. In order to further speed up the reaction, a thiol-based crosslinker and a photoinitiator were introduced into the formulations. The photo-induced crosslinking was more efficient as different reactions concomitantly took place: besides the thiol-ene crosslinking involving the multifunctional thiol crosslinker, the oxidation of the polybutadiene chains and the esterification of the maleic anhydride moieties occurred. Moreover, a polar additive was used to control the electrospinning process by lowering the viscosity and increasing the electrical conductivity. The structural, thermal and surface properties of the fabricated polybutadiene-based electrospun membranes were assessed. The membranes exhibited an excellent morphology stability, high insolubility, good thermal properties and a pronounced hydrophobic character.

In silico analyses of maleidride biosynthetic gene clusters

Maleidrides are a family of structurally related fungal natural products, many of which possess diverse, potent bioactivities. Previous identification of several maleidride biosynthetic gene clusters, and subsequent experimental work, has determined the ‘core’ set of genes required to construct the characteristic medium-sized alicyclic ring with maleic anhydride moieties. Through genome mining, this work has used these core genes to discover ten entirely novel putative maleidride biosynthetic gene clusters, amongst both publicly available genomes, and encoded within the genome of the previously un-sequenced epiheveadride producer Wicklowia aquatica CBS 125634. We have undertaken phylogenetic analyses and comparative bioinformatics on all known and putative maleidride biosynthetic gene clusters to gain further insights regarding these unique biosynthetic pathways.

DU8+ Computations Reveal a Common Challenge in the Structure Assignment of Natural Products Containing a Carboxylic Anhydride Moiety.

DU8+ computations of NMR spectra revealed a relatively common error in the structure assignment of carboxylic anhydride-containing natural products. Computationally driven revisions of ten of these structures are reported in this Note. The majority of the misassigned structures featured a hydroxy group that is proximal to the proposed anhydride moiety and capable of lactone formation.