Carboxylic Derivatives Research Articles

Effects of long-term intake of whole wheat and aleurone-enriched Chinese steamed bread on gut microbiome and liver metabolome in mice fed high-fat diet

The protective effects of whole wheat flour steamed bread (WWF) and aleurone-enriched wheat flour steamed bread (AWF) on gut microbiota and metabolomic disorders were investigated in long-term high-fat diet (HFD) mice. The results showed that AWF and WWF significantly ameliorated dyslipidemia, hepatic oxidative stress, and damage in HFD-fed mice. The fecal microbiome analysis showed that AWF and WWF significantly increased diversity in the gut microbiota and altered the structure of the gut microbiota. An increase in Bacteroidetes (by 31% and 34%) and decrease in Firmicutes (by 17% and 17%) were observed in the AWF and WWF groups, respectively. Liver metabolomics demonstrated that AWF and WWF upregulated carboxylic acids and derivatives and organooxygen compounds, and downregulated fatty acyl compounds. Moreover, WWF significantly modulated the concentrations of steroids and steroid derivatives, and glycerophospholipids. Overall, our findings suggest that AWF and WWF dramatically altered hepatic metabolism concurrent with shifts in specific gut bacteria in C57BL/6J mice, exhibiting potential as functional foods for the prevention of metabolic disorders induced by a long-term HFD. Despite some differences, the AWF is generally able to achieve the same level of health benefits as the WWF.

Blapsimidazolium A: A new imidazolium carboxylate derivative with anti-inflammatory activity from medicinal insect Blaps rynchopetera

Blaps rynchopetera Fairmaire is a medicinal insect of Yi-nationality medicine used for a long time in Yunnan, China. In the present study, a new blapsimidazolium A (1), together with twelve known N-containing compounds (2−13), were isolated from this insect. The structures were elucidated by extensive spectroscopic analyses (1D and 2D NMR, HR-MS) and comparisons with the reported literature. Blapsimidazolium A was identified as racemic mixture by optical rotation and chiral analysis. Blapsimidazolium A (1) has a unique architecture containing an imidazolium carboxylate moiety. The results of molecular docking showed that blapsimidazolium A bound well to IL-1β, IL-6 and iNOS. The racemates of (±)-blapsimidazolium A (1) exerted anti-inflammatory activity in LPS-stimulated THP-1 cells by significantly decreasing the production of the proinflammatory cytokines IL-1β, IL-6 and iNOS. This is the first report describing the anti-inflammatory activity of this type imidazolium carboxylate derivative.

Synthesis, Characterization, and Comparison of Disinfectant Bioactivity Test of Two Triphenyltin(IV) Compounds

This paper aims to report the synthesis of two new organotin(IV) carboxylate derivatives, triphenyltin(IV) 4-aminobenzoate (2) and triphenyltin(IV) 4-nitrobenzoate (3) and to examine their antibacterial activity as a disinfectant. These compounds were prepared by reacting triphenyltin(IV) hydroxide (1) with 4-aminobenzoic acid and 4-nitrobenzoic acid, respectively. Compound (2) was obtained as a yellow solid with a yield of 84.09% and compound (3) in the form of a white solid with a yield of 80.70%. These compounds were well characterized using UV-Vis spectrometry, FT-IR spectrometry and NMR spectroscopy. The bioactivity test as a disinfectant was tested against Salmonella typhosa and Staphylococcus aureus. The activity test was carried out by measuring the optical density (OD) of the tested compounds with concentration variations of 5x10-3, 1x10-3, and 5x10-4 M in methanol and 5% dimethyl sulfoxide (DMSO), commercial Wipol (2.5% pine oil) was used as a positive control with observations monitored at contact times of 0, 5, 10, and 15 minutes. The results showed that of both compounds were active against the two bacteria compared to the positive control with compound 3 found to be more active than compound 2.

Chiral quaternary ammonium ionic liquids derived from natural dehydroabietylamine and their potential application in chiral molecular recognition

A series of chiral ionic liquids (CILs) based on a quaternary ammonium core substituted with (+)-dehydroabietylamine (DAA) moiety have been synthesized, which are used for the chiral discrimination of non-ionic racemic carboxylic acid and derivatives. The enantioselective recognition ability of the obtained DAA-CILs was investigated using (rac)-mandelic acid and its derivatives as substrates. The results showed that the choice of the anion was crucial for the chiral discrimination of these DAA-CILs. In general, bistrifluoromethanesulfonimide anion (NTf2-) resulted in the improvement and a broad spectrum of enantioselectivity of the CILs. The alkyl chain attached to the DAA group and quaternary ammonium cation was also responsible for the chiral discrimination, and the C3 or C4 carbon chain was favorable for the chiral molecule recognition ability of the CILs. A molecular simulation of the diastereomeric interactions between the selected [DAAPrTMA]NTf2 CIL and racemic α-methoxy mandelic acid (α-MPAA) achieved a well understanding of the chiral recognition mechanism. Additionally, the optical purity of α-MPAA could be detected via NMR analysis easily and quickly. This work leads us to develop new CILs with good molecular recognition ability, DAA-based quaternary ammonium salts.

Untargeted metabolism approach reveals difference of varieties of bud and relation among characteristics of grafting seedlings in Camellia oleifera.

Camellia oleifera is one of the essential wood oil trees in the world. C.oleifera was propagated by nurse seedling grafting. Since the scion of C.oleifera had a significant regulated effect on the properties of rootstock after grafting and impacted on the growth of the grafted seedlings, it was necessary to understand the characteristics of buds among varieties to cultivate high-quality grafted seedlings. The metabolome was thought to be a powerful tool for understanding connecting phenotype-genotype interactions, which has an important impact on plant growth and development. In this study, UPLC-MS was used to determine the metabolites of the apical buds of CL3, CL4, CL40, and CL53 spring shoots after 30 days of sprout and to measure the growth characteristics of roots and stems after grafting. Metabolomics analysis revealed 554 kinds of metabolites were significant differences among four varieties, and 29 metabolic pathways were identified to have significant changes (p< 0.05), including carboxylic acids and derivatives, fatty Acyls, organooxygen compounds, and prenol lipids metabolites. The metabolites appeared in all varieties, including phenethyl rutinoside in glycosyl compounds and hovenidulcioside A1 in terpene glycosides. Metabolite-metabolite correlations in varieties revealed more complex patterns in relation to bud and enabled the recognition of key metabolites (e.g., Glutamate, (±)Catechin, GA52, ABA, and cs-Zeatin) affecting grafting and growth ability. Each variety has a unique metabolite type and correlation network relationship. Differentiated metabolites showed different growth trends for development after grafting. Many metabolites regulate the growth of scions in buds before grafting, which plays a crucial role in the growth of seedlings after grafting. It not only regulates the growth of roots but also affects the development of this stem. Finally, those results were associated with the genetic background of each cultivar, showing that metabolites could be potentially used as indicators for the genetic background, indicating that metabolites could potentially be used as indicators for seedling growth characteristics. Together, this study will enrich the theoretical basis of seedling growth and lay a foundation for further research on the molecular regulation mechanism interaction between rootstock and scion, rootstock growth, and the development of grafted seedlings after grafting.

Photocatalytic direct borylation of carboxylic acids

The preparation of high value-added boronic acids from cheap and plentiful carboxylic acids is desirable. To date, the decarboxylative borylation of carboxylic acids is generally realized through the extra step synthesized redox-active ester intermediate or in situ generated carboxylic acid covalent derivatives above 150 °C reaction temperature. Here, we report a direct decarboxylative borylation method of carboxylic acids enabled by visible-light catalysis and that does not require any extra stoichiometric additives or synthesis steps. This operationally simple process produces CO2 and proceeds under mild reaction conditions, in terms of high step economy and good functional group compatibility. A guanidine-based biomimetic active decarboxylative mechanism is proposed and rationalized by mechanistic studies. The methodology reported herein should see broad application extending beyond borylation.

Nontargeted metabolomic evidence for antagonism between tetracycline and its resistance bacteria underlying their obesogenic effects on Caenorhabditis elegans

Environmental antibiotics raise serious health concerns due to their contribution to the obesity prevalence. Moreover, antibiotics promote antibiotic-resistance bacteria (ARB) which represent another emerging pollutant. However, the interaction between antibiotic and ARB in the obesogenic effects remained unexplored. In the present study, the obesogenic effects of tetracycline antibiotic (TCH) and ARB containing tetA were studied on C. elegans, and E. coli OP50 (OP50) was referred as a normal bacterial food. Results showed that TCH stimulated nematode triglyceride contents, while ARB alone had no significant influences. The combination of TCH and ARB showed less obesogenic effects than TCH alone, showing antagonism. Biochemical assays showed that the combination of TCH and ARB showed similar effects to ARB alone, and had less increases in lipid metabolism enzymes or metabolites than those of TCH or ARB alone, supporting the antagonism. In the nontargeted metabolomic analysis, TCH with ARB showed less significantly changed metabolites (SCMs) in the nematodes than TCH or ARB alone, partially explaining the antagonism. The metabolomic results also pointed out the significant involvement of amino acids, the carboxylic acids and derivatives, and also the benzene and substituted derivatives in the obesogenic effects of TCH and ARB. The findings of the present study provided a direct support for interaction between antibiotics and ARB underlying their health risks.

Asymmetric Three-Component Reaction of Enynal with Alcohol and Imine as An Expeditious Track to Afford Chiral α-Furyl-β-amino Carboxylate Derivatives

Herein, we report an achiral dirhodium complex and chiral phosphoric acid cooperatively catalyzed asymmetric three-component reaction of enynal with alcohol and imine, affording chiral α-furyl-β-amino carboxylates in good to high yields with generally excellent stereoselectivity. The successful introduction of enynal as a carbene precursor in this reaction provides an expeditious track to prepare complex furan derivatives with adjacent quaternary and tertiary stereocenters. The starting materials are stable and readily available, and the method features 100% atom economy with high bond-formation efficiency. This is a highly enantioselective gem-difunctionalization reaction of metal carbene generated in situ from enynal. These generated chiral products could be smoothly converted to polycyclic frameworks and drug-conjugated derivatives through different cycloaddition reactions.

Titanium‐Catalyzed Exhaustive Reduction of Oxo‐Chemicals

AbstractCatalytic reduction of carboxylic acids and derivatives all the way to their corresponding methyl‐compounds is very rare and still challenging for homogeneous transition‐metal catalysis. Herein, we report an unprecedented and general catalytic exhaustive reduction of carboxylic functional group straightforwardly to a methyl group. This reaction was achieved using earth‐abundant and readily available titanium as a catalyst. Our system has broad functional group tolerance and works for various other types of oxo‐chemicals such as alcohols, aldehydes, ketones, lactones, and carboxylates (&gt;100 examples). Preliminary mechanistic studies revealed that the in situ‐generated TiIII−H species was vital for this transformation.

Titanium-Catalyzed Exhaustive Reduction of Oxo-Chemicals.

Catalytic reduction of carboxylic acids and derivatives all the way to their corresponding methyl-compounds is very rare and still challenging for homogeneous transition-metal catalysis. Herein, we report an unprecedented and general catalytic exhaustive reduction of carboxylic functional group straightforwardly to a methyl group. This reaction was achieved using earth-abundant and readily available titanium as a catalyst. Our system has broad functional group tolerance and works for various other types of oxo-chemicals such as alcohols, aldehydes, ketones, lactones, and carboxylates (>100 examples). Preliminary mechanistic studies revealed that the in situ-generated TiIII -H species was vital for this transformation.

Paracetamol adsorption on C60 fullerene and its derivatives: In silico insights

Fullerene-C60 and its heteroatom decorated forms have been widely investigated as drug delivery vehicles and for sensor applications. Further, in the literature carboxylated or carboxylic derivatives of fullerenes have found a special place for biological applications due to their promising water-soluble properties. In the scope of this study, we examined the interaction between paracetamol (acetaminophen) which is a widely prescribed drug to manage acute and chronic pain conditions and C60, silicon doped fullerene (SiC59) and (1,2-methanofullerene C60)-61-carboxylic acid (C60-CH-COOH) using density functional theory calculations. Stability evaluations, electronic and structural properties were carried out by analyzing binding energies, frontier molecular orbitals and natural bond orbitals. It was found that silicon doping on the surface of C60 enhanced the adsorption strength of paracetamol and SiC59 is quite sensitive to the presence of paracetamol drug molecule.

6-Heterocyclic carboxylic ester derivatives of gliotoxin lead to LSD1 inhibitors in gastric cancer cells

Gliotoxin is a representative compound of the epipolythiodioxopiperazine (ETP) class of fungal metabolites. Histone Lysine Specific Demethylase 1 (LSD1) is highly expressed in a variety of cancers. Herein, a series of 6-heterocyclic carboxylic ester derivatives of gliotoxin was designed and synthesized as new LSD1 inhibitors and their biological evaluations in human gastric MGC-803 and HGC-27 cells were carried out. All of the derivatives effectively suppressed the enzymatic activities of LSD1. In particular, compound 4e exhibited excellent LSD1 inhibition with IC50 = 62.40 nM, as well as anti-proliferation against MGC-803 and HGC-27 cells with IC50 values of 0.31 μM and 0.29 μM, respectively. 4e also had a remarkable capacity to inhibit the colony formation, suppress migration and induce the apoptosis of these two cancer cell lines. In sum, our findings identified and characterized the 6-heterocyclic carboxylic ester derivatives of gliotoxin as potent and cellular active LSD1 inhibitors, which may provide a novel chemotype of LSD1 inhibitors for gastric cancer treatment.

Photo‐Mediated Reduction of Carbon Dioxide to Formic and Other Carboxylic Acids by Ni‐Catalysis with Chelating Ligand

In this minireview, photo-mediated reductions of CO2 to formic and other carboxylic acids by Ni-chelate catalysts were discussed with mechanistic details. Formic and other carboxylic acid products are formed exclusively over CO by insertion of CO2 in Ni−H/Ni−C bonds in these Ni-catalysed light-mediated CO2 reductions. Role of chelating ligands in modulating the catalytic efficiency and product selectivity of such catalysis has also been encompassed in the minireview.

Spontaneous Decarboxylation of Ferrocenecarboxylate using 1,4‐Benzoquinone as Oxidant: Application to the Chemical Grafting of Glassy Carbon Surfaces

AbstractThe covalent modification of glassy carbon electrode with ferrocenyl moieties was performed in acetonitrile using a mixture of ferrocenecarboxylate (FcCOO−) and ferrocenecarboxylic acid (FcCOOH). This process is activated by 1,4‐benzoquinone (Q), which plays the role of oxidant. The carboxylate induces the redox reduction of the quinone whereas an excess of the carboxylic acid drives the protonation of the reduced quinone to yield hydroquinone (QH2) as a reaction product. Due to the homogeneous oxidation of the carboxylate derivative, carbon dioxide and ferrocenyl radicals (Fc⋅) are released, such as occurs in the classical Kolbe reaction. The generation of ferrocenyl radicals allows the chemical derivatization of non‐connected glassy carbon surfaces. The homogeneous redox reaction between the 1,4‐benzoquinone and ferrocenecarboxylate proceeded slowly and permitted the covalent attachment of a thin film with ferrocenyl moieties, whose presence on the carbon surface was evidenced from cyclic voltammetry and atomic force microscopy (AFM) measurements.

Adsorption Behavior of 9-Anthracenecarboxylic Acid on (110) Rutile TiO2

The adsorption behavior of 9-anthracenecarboxylic acid (AnCA) on a rutile TiO2 (110) surface has been investigated with scanning tunneling microscopy (STM) at room temperature. Upon deposition, the molecules adsorb, resulting in a commensurate herringbone c-(2 × 2) structure, as confirmed by low-energy electron diffraction (LEED). Annealing of the sample below the desorption point causes irreversible superstructure derangement. Thermally programmed desorption (TPD) reveals that, after prior decomposition on the surface, AnCA molecules desorb into anthracenes and carboxyl acid derivatives.

A Rapid, Highly Sensitive and Selective Phosgene Sensor Based on 5,6-Pinenepyridine.

The toxicity of phosgene (COCl2 ) combined with its extensive use as a reactant and building block in the chemical industry make its fast and accurate detection a prerequisite. We have developed a carboxylic derivative of 5,6-pinenepyridine which is able to act as colorimetric and fluorimetric sensor for phosgene in air and solution. For the first time, the formation of a pyrido-[2,1-a]isoindolone was used for this purpose. In solution, the sensing reaction is extremely fast (under 5 s), selective and highly sensitive, with a limit of detection (LOD) of 9.7 nM/0.8 ppb. When fixed on a solid support, the sensor is able to detect the presence of gaseous phosgene down to concentrations of 0.1 ppm, one of the lowest values reported to date.

Photocatalytic Carboxylation with CO2: A Review of Recent Studies

AbstractCarbon dioxide (CO2) is the main byproduct from the combustion of fossil fuels, the excessive emission into the atmosphere is regarded as primary causes for global warming and climate change. On the other hand, CO2 is also a readily available, non‐toxic, low‐cost C1 source, and widely used in synthetic chemistry to afford value carboxylic acids and derivatives by photocatalysis CO2 transformation under light irradiation. Herein, we present a summarization for the recent advances and achievements in the area of photocatalytic carboxylation of unsaturated hydrocarbons, organo(pseudo)halides, carbonyl compounds, tetraalkyl ammonium salt, and C(sp3) C−O bonds with CO2. We also discuss the mechanisms of such reactions, which will help us to comprehend the specific process of carboxylation. We hope the summary of these methods will further stimulate future research in this sought‐after area.

Versatile Conversions of Substituents in Guaiazulene: Synthesis of Carboxylic Acid Derivatives with Controlled Regiospecific Reactivities

Abstract Azulene derivatives such as guaiazulene have unique properties and thus play important roles in electronic materials. However, the application of these materials is limited by the lack of functionalization approaches for guaiazulene extracted from natural products. Herein, we report a method for the synthesis of three guaiazulene carboxylic acid derivatives in four to five steps by controlling the reactivity of guaiazulene. 7-Isopropyl-4-methylazulene-1-carboxylic acid was prepared by protecting the C-3 position of guaiazulene with an ester group to inhibit unexpected reactions. We also introduced a carboxyl group at the inactive C-2 position of guaiazulene using a boryl group as a key intermediate. The C4-methyl group of guaiazulene was converted to a formyl group utilizing the acidity of the protons on the C4-methyl group. By protecting the C-3 position of guaiazulene with a tosyl group, 7-isopropyl-1-methylazulene-4-carboxylic acid was synthesized via Kraus-Pinnick oxidation. Ultraviolet/visible spectra of the synthesized guaiazulene carboxylic acids indicate that the longest wavelength at maximum absorption varied depending on the substitution position of the carboxyl group in guaiazulene. Guaiazulene carboxylic derivatives will serve as building blocks for the development of guaiazulene-based materials because the carboxyl group can be converted to various functional groups.

Dibutylstannanediyl (2Z,2′Z)-bis(4-(benzylamino)-4-oxobut-2-enoate inhibits prostate cancer progression by activating p38 MAPK/PPARα/SMAD4 signaling

Organotin (IV) compounds are a focus of research for potential use in cancer chemotherapy. Here, we established anticancer profile of dibutyltin (IV) carboxylate derivatives in prostate cancer (PCa) model. We determined cytotoxicity of a library of dibutyltin (IV) carboxylate derivatives and observed that dibutylstannanediyl (2Z,2′Z)-bis(4-(benzylamino)-4-oxobut-2-enoate (Ch-620; 10 μM) was minimally toxic to normal fibroblasts. Ch-620 (1–1.25 μM) inhibited proliferation of PCa and melanoma cells on short- and long-term exposures with induction of cell cycle arrest. Ch-620 treatment increased population of apoptotic cells, as assessed by flow cytometry, and activated caspase 3. Proteomics showed activation of PPARα, with repression of SMAD4 and integrin β5 (ITGB5) in Ch-620-treated PCa cells. Further analysis demonstrated that Ch-620 resulted in phosphorylation of p38 MAPK, upregulation of PPARα and decreased expression of SMAD4 and ITGB5 with reduced migration of PCa cells. In vivo studies in PC3M grafted athymic nude mice showed that Ch-620 (5 μg/week; 7 weeks) treatment reduced tumor growth as opposed to untreated controls. Immunoblot analysis of tumors demonstrated upregulated p-p38 MAPK and PPARα, followed by a decline in SMAD4 and ITGB5. Immunohistochemistry reinforced these results with increased caspase 3 and p-p38 MAPK and diminished Ki67 staining in Ch-620 treated animals. Taken together, our data indicate that Ch-620 inhibited proliferation of PCa through modulation of MAPK/PPARα/SMAD4 signaling. Organotin (IV) carboxylate compounds; specifically Ch-620 can be a potential anticancer agent for the treatment of PCa subject to detailed pre-clinical and clinical investigations. This unlocks prospects for the development of new tin-based drugs in cancer therapeutics.

Chemoselective Oxyfunctionalization of Functionalized Benzylic Compounds with a Manganese Catalyst.

Whilst allowing for easy access to synthetically versatile motifs and for modification of bioactive molecules, the chemoselective benzylic oxidation reactions of functionalized alkyl arenes remain challenging. Reported in this study is a new non‐heme Mn catalyst stabilized by a bipiperidine‐based tetradentate ligand, which enables methylene oxidation of benzylic compounds by H2O2, showing high activity and excellent chemoselectivity under mild conditions. The protocol tolerates an unprecedentedly wide range of functional groups, including carboxylic acid and derivatives, ketone, cyano, azide, acetate, sulfonate, alkyne, amino acid, and amine units, thus providing a low‐cost, more sustainable and robust pathway for the facile synthesis of ketones, increase of complexity of organic molecules, and late‐stage modification of drugs.