Aromatic Methyl Esters Research Articles

Enzymatic acylation of cyanidin-3-O-glucoside with aromatic and aliphatic acid methyl ester: Structure–stability relationships of acylated derivatives

Anthocyanins are water-soluble pigments, but they tend to be unstable in aqueous solutions. Modification of their molecular structure offers a viable approach to alter their intrinsic properties and enhance stability. Aromatic and aliphatic acid methyl esters were used as acyl donors in the enzymatic acylation of cyanidin-3-O-glucoside (C3G), and their analysis was conducted using ultraperformance liquid chromatography–mass spectrometry (UPLC-MS). The highest conversion rate achieved was 96.41 % for cyanidin-3-O-(6″-feruloyl) glucoside. Comparative evaluations of stability revealed that aromatic acyl group–conjugated C3G exhibited superior stability enhancement compared with aliphatic acyl group derivatives. The stability of aliphatic C3G decreased with increasing carbon chain length. The molecular geometries of different anthocyanins were optimized, and energy level calculations using density functional theory (DFT) identified their sites with antioxidant activities. Computational calculations aligned with the in vitro antioxidant assay results. This study provided theoretical support for stabilizing anthocyanins and broadened the application of acylated anthocyanins as food colorants and nutrient supplements.

Carbon-Nitrogen Bond Formation Using Sodium Hexamethyldisilazide: Solvent-Dependent Reactivities and Mechanisms.

The solvent-dependent reactivity of sodium hexamethyldisilazide (NaHMDS) toward carbon-centered electrophiles reveals reactions that are poorly represented or unrepresented in the literature, including direct aminolysis of aromatic methyl esters to give carboxamides, nitriles, or amidines, depending on the choice of solvent. SNAr substitutions of aryl halides and opening of terminal epoxides are also examined. A combination of 1H and 29Si nuclear magnetic resonance (NMR) spectroscopic studies using [15N]NaHMDS, kinetic studies, and computational studies reveals the complex mechanistic basis of the preferences for simple aryl carboxamides in toluene and dimethylethylamine and arylnitriles or amidines in tetrahydrofuran (THF). A prevalence of dimer- and mixed dimer-based chemistry even starting from the observable NaHMDS monomer in THF solution is notable.

Phytoconstituents from Moringa oleifera fruits target ACE2 and open spike glycoprotein to combat SARS-CoV-2: An integrative phytochemical and computational approach.

Therapeutic drugs based on natural products for the treatment of SARS-CoV-2 are currently unavailable. This study was conducted to develop an anti-SARS-CoV-2 herbal medicine to face the urgent need for COVID-19 treatment. The bioactive components from ethanolic extract of Moringa oleifera fruits (MOFs) were determined by gas chromatography-mass spectroscopy (GC-MS). Molecular-docking analyses elucidated the binding effects of identified phytocomponents against SARS-CoV-2 spike glycoprotein (PDB ID: 6VYB) and human ACE2 receptor (PDB ID: 1R42) through the Glide module of Maestro software. GC-MS analysis unveiled the presence of 33 phytocomponents. Eighteen phytocomponents exhibited good binding affinity toward ACE2 receptor, and thirteen phytocomponents had a high affinity with spike glycoprotein. This finding suggests that the top 11 hits (Docking score ≥ -3.0kcal/mol) could inhibit SARS-CoV-2 propagation. Intriguingly, most of the phytoconstituents displayed drug-likeness with no predicted toxicity. However, further studies are needed to validate their effects and mechanisms of action. PRACTICAL APPLICATIONS: Moringa oleifera (MO) also called "drumstick tree" has been used as an alternative food source to combat malnutrition and may act as an immune booster. GC-MS analysis unveiled that ethanolic extract of Moringa oleifera fruits (MOFs) possessed 33 active components of pyridine, aromatic fatty acid, oleic acid, tocopherol, methyl ester, diterpene alcohol, triterpene and fatty acid ester and their derivatives, which have various pharmacological and medicinal values. Virtual screening study of phytocomponents of MOF with human ACE2 receptor and SARS-CoV-2 spike glycoprotein exhibited good binding affinity. Based on molecular docking, the top 11 hits (Docking score ≥-3.0kcal/mol) might serve as potential lead molecules in antiviral drug development. Intriguingly, most of the phytoconstituents displayed drug-likeness with no predicted toxicity. Thus, MOF might be used as a valuable source for antiviral drug development to combat COVID-19, an ongoing pandemic.

Synthesis and Antibacterial Activity of 5-Aryl-4-[hydroxy(4-chlorophenyl)methylene]-1-[2-(1H-indol-3-yl)ethyl]pyrrolidine-2,3-diones

The reaction of tryptamine with aromatic aldehydes and 4-chlorobenzoylpyruvic acid methyl ester led to the formation of 5-aryl-4-[hydroxy-(4-chlorophenyl)methylene]-1-[2-(1H-indol-3-yl)ethyl]pyrrolidine-2,3-diones. The resulting compounds were tested for antimicrobial activity.

Applications of γ,δ-Unsaturated Ketones Synthesized by Copper-Catalyzed Cascade Addition of Vinyl Grignard Reagents to Esters.

γ,δ-Unsaturated ketones, so-called homoallylic ketones, have served as versatile building blocks for the synthesis of a variety of heterocycles, carbocycles, natural products, and reactive intermediates. Procured by a variety of processes, including conjugate addition of vinyl organometallic reagents to unsaturated ketones, allylation of silyl enol ethers, and rearrangements, homoallylic ketones are often synthesized by step-intensive methods. The cascade addition of 2 equiv of vinyl Grignard reagent to a carboxylate was reported by the Lubell laboratory in 2003 to give effective access to homoallylic ketones from a variety of aromatic, aliphatic, and α-amino methyl esters. Employing readily accessible vinyl magnesium halides in the presence of a catalytic amount of copper salt, this cascade reaction provides high yields of homoallylic ketones with minimal side product by a process featuring the assembly and collapse of a tetrahedral intermediate with expulsion of alkoxide ion, followed by conjugate addition to the resulting enone. Application of the cascade reaction to the synthesis of various homoallylic ketones has provided versatile building blocks for the synthesis of targets for different applications. For example, by employing (hetero)aryl di- and tricarboxylates as precursors, copper-catalyzed cascade additions have provided donor-acceptor and star-shaped monomers for optical-electronic materials. Amino ester starting materials have given homoallylic ketones for the synthesis of various peptidomimetics, including heteroarylalanines, hydroxyethylene isoesters, and diazepinone turn mimics. Moreover, anthranilate has served as building block to prepare various pyrrole, quinoline, benzodiazepine, and benzotriazepine heterocyles. In addition, cascade additions on hydroxyprolinates have given access to bipyrrole precursors of the prodigiosin family of natural products. In the interest to highlight the utility of the copper-catalyzed cascade addition of vinyl Grignard reagents to carboxylates, this Account provides details on the broad scope of substrates that deliver homoallylic ketone products as well as an overview of the wide range of applications in which this method may impact including materials and peptide science, heterocycle and natural product synthesis, and medicinal chemistry.

Reductive Cleavage of Aromatic and Heteroaromatic Ester Functions via Copper-Catalyzed Proto-Decarbomethoxylation.

An unprecedented catalytic reductive cleavage of aromatic and heteroaromatic methyl ester functions was successfully achieved with a cheap, nontoxic, and air-stable Cu(OAc)2 catalyst. This reaction is fast, features good functional group tolerance, does not require inert atmosphere or anhydrous solvent, and can be scaled up to 1 g. Moreover, carboxylic acids and t-butyl esters also reacted smoothly under these conditions.

Molecular characterization of primary humic-like substances in fine smoke particles by thermochemolysis–gas chromatography–mass spectrometry

In this study, the molecular structures of primary humic-like substances (HULIS) in fine smoke particles emitted from the combustion of biomass materials (including rice straw, corn straw, and pine branches) and coal, and atmospheric HULIS were determined by off-line tetramethylammonium hydroxide thermochemolysis coupled with gas chromatography and mass spectrometry (TMAH-GC/MS). A total of 89 pyrolysates were identified by the thermochemolysis of primary and atmospheric HULIS. The main groups were polysaccharide derivatives, N-containing compounds, lignin derivatives, aromatic acid methyl ester, aliphatic acid methyl ester, and diterpenoid derivatives. Both the type and distribution of pyrolysates among primary HULIS were comparable to those in atmospheric HULIS. This indicates that primary HULIS from combustion processes are important contributors to atmospheric HULIS. Some distinct differences were also observed. The aromatic compounds, including lignin derivatives and aromatic acid methyl ester, were the major pyrolysates (53.0%–84.9%) in all HULIS fractions, suggesting that primary HULIS significantly contributed aromatic structures to atmospheric HULIS. In addition, primary HULIS from biomass burning (BB) contained a relatively high abundance of lignin and polysaccharide derivatives, which is consistent with the large amounts of lignin and cellulose structures contained in biomass materials. Aliphatic acid methyl ester and benzyl methyl ether were prominent pyrolysates in atmospheric HULIS. Moreover, some molecular markers of specific sources were obtained from the thermochemolysis of primary and atmospheric HULIS. For example, polysaccharide derivatives, pyridine and pyrrole derivatives, and lignin derivatives can be used as tracers of fresh HULIS emitted from BB. Diterpenoid derivatives are important markers of HULIS from pine wood combustion sources. Finally, the differences in pyrolysate types and the distributions between primary and atmospheric HULIS suggested that the primary HULIS would undergo many atmospheric processes to reconstruct the macromolecular organic matter in atmospheric aerosols.

Assembly and inhibitory activity of monovalent mannosides terminated with aromatic methyl esters: The effect of naphthyl groups

A series of monovalent α-D-mannoside ligands terminated with aromatic methyl esters have been synthesized in excellent yields using the Cu(I) catalyzed azide-alkyne 1,3-dipolar cycloaddition (“click chemistry”). These mannosides were designed to have a unique aglycone moiety (tail) that combines a triazole ring attached to aromatic methyl esters via a six carbon alkyl chain. The mannose unit of these ligands was linked at the ortho, meta, and para positions of substituted methyl benzoates and 1-, 3-, and 6-substituted methyl 2-napthaoates. In hemagglutination assays, ligands (32A-38A) showed better inhibitory activities than the standard inhibitor, methyl α-D-mannopyranoside. Overall, the naphthyl-based mannoside ligand (37A) showed the best activity and therefore merits further development.

Enzymatic Acylation of Anthocyanin Isolated from Black Rice with Methyl Aromatic Acid Ester as Donor: Stability of the Acylated Derivatives.

The enzymatic acylation of anthocyanin from black rice with aromatic acid methyl esters as acyl donors and Candida antarctica lipase B was carried out under reduced pressure. The highest conversion of 91% was obtained with benzoic acid methyl ester as acyl donor; cyanidin 3-(6″-benzoyl)-glucoside, cyanidin 3-(6″-salicyloyl)-glucoside, and cyanidin 3-(6″-cinnamoyl)-glucoside were successfully synthesized. This is the first report on the enzymatic acylation of anthocyanin from black rice with methyl aromatic esters as acyl donors and lipase as biocatalyst. Furthermore, the acylation with aromatic carboxylic acids enhanced both the thermostability and light resistivity of anthocyanin. In particular, cyanidin 3-(6″-cinnamoyl)-glucoside was the most stable among the three acylated anthocyanins synthesized.

Synthesis and antihypoxic activity of 5-aryl-4-aroyl-3-hydroxy-1-[2-(2-hydroxyethoxy)ethyl]-3-pyrrolin-2-ones

Reactions of 2-(2-aminoethoxy)ethanol with mixtures of an aromatic aldehyde and aroylpyruvic acid methyl ester have afforded 5-aryl-4-aroyl-3-hydroxy-1-[2-(2-hydroxyethoxy)ethyl]-3-pyrrolin-2-ones. Antihypoxic activity of the synthesized compounds has been studied.

Experimental determination and prediction of (solid + liquid) phase equilibria for binary mixtures of aromatic and fatty acids methyl esters

Solid–liquid equilibria for binary mixtures of {methyl stearate (1) + biphenyl (2)}, {methyl stearate (1) + naphthalene (2)}, {methyl palmitate (1) + biphenyl (2)} and {methyl palmitate (1) + naphthalene (2)} were measured using differential scanning calorimeter. Simple eutectic behaviours for these systems were observed. The experimental results were correlated by means of the NRTL, Wilson, UNIQUAC and ideal models. The root-mean-square deviations of the solubility temperatures for all measured data vary from 0.5477 K (for UNIQUAC model) to 7.79 K; the deviations depend on the binary system studied and particular model used. The best solubility correlation was obtained with UNIQUAC model and this observation confirms previous results.

ChemInform Abstract: Facile Preparation of Aromatic Esters from Aromatic Bromides with Ethyl Formate or DMF and Molecular Iodine via Aryllithium.

Abstract Various aromatic bromides were treated with n -BuLi and subsequently with ethyl formate, followed by the reaction with ethanol and molecular iodine in the presence of K 2 CO 3 to provide the corresponding aromatic ethyl esters in good yields. Moreover, aromatic bromides could be transformed into the corresponding aromatic methyl esters in good yields by the treatment with n -BuLi and subsequently with DMF, followed by the reaction with methanol, molecular iodine, and K 2 CO 3 . Some aromatics could be also converted into the corresponding aromatic esters in good yields by the treatment with n -BuLi, and subsequently with ethyl formate or DMF, followed by the reaction with molecular iodine and K 2 CO 3 . The present reactions offer a novel route for the transition-metal-free, carbon-monoxide-free, and therefore environmentally benign one-pot conversion of aromatic bromides and aromatics into aromatic esters.

Facile preparation of aromatic esters from aromatic bromides with ethyl formate or DMF and molecular iodine via aryllithium

Various aromatic bromides were treated with n-BuLi and subsequently with ethyl formate, followed by the reaction with ethanol and molecular iodine in the presence of K2CO3 to provide the corresponding aromatic ethyl esters in good yields. Moreover, aromatic bromides could be transformed into the corresponding aromatic methyl esters in good yields by the treatment with n-BuLi and subsequently with DMF, followed by the reaction with methanol, molecular iodine, and K2CO3. Some aromatics could be also converted into the corresponding aromatic esters in good yields by the treatment with n-BuLi, and subsequently with ethyl formate or DMF, followed by the reaction with molecular iodine and K2CO3. The present reactions offer a novel route for the transition-metal-free, carbon-monoxide-free, and therefore environmentally benign one-pot conversion of aromatic bromides and aromatics into aromatic esters.

Synthesis and antimicrobial activity of 5-aryl-4-acyl(heteroyl)-3-hydroxy-1- (3-ethoxypropyl)-3-pyrrolin-2-ones

A series of 5-aryl-4-acyl(heteroyl)-3-hydroxy-1-(3-ethoxypropyl)-3-pyrrolin-2-ones were synthesized using the reaction of 3-ethoxypropylamine with a mixture of aromatic aldehyde and methyl esters of acyl(heteroyl)- pyruvic acid. The antimicrobial activity of the synthesized compounds was studied.

Direct aerobic photo-oxidative syntheses of aromatic methyl esters from methyl aromatics using anthraquinone-2,3-dicarboxylic acid as organophotocatalyst

This paper reports a useful method for facile direct syntheses of aromatic methyl esters from methyl aromatics by aerobic photo-oxidation using anthraquinone-2,3-dicarboxylic acid as an organophotocatalyst.

ChemInform Abstract: Direct Aerobic Photo‐Oxidative Synthesis of Aromatic Methyl Esters from Methyl Aromatics via Dimethyl Acetals.

A useful method for facile synthesis of aromatic methyl esters from methyl aromatics via dimethyl acetals by aerobic photo-oxidation using inexpensive and easily handled CBr4 as catalyst is reported. This is the first example for direct preparation of the corresponding aromatic methyl esters from methyl aromatics.

Direct Aerobic Photo-Oxidative Synthesis of Aromatic Methyl Esters from Methyl Aromatics via Dimethyl Acetals

A useful method for facile synthesis of aromatic methyl esters from methyl aromatics via dimethyl acetals by aerobic photo-oxidation using inexpensive and easily handled CBr(4) as catalyst is reported. This is the first example for direct preparation of the corresponding aromatic methyl esters from methyl aromatics.

An Oxidation of Benzyl Methyl Ethers with NBS that Selectively Affords Either Aromatic Aldehydes or Aromatic Methyl Esters

Either mono- or dibromination of benzyl methyl ethers can be achieved by controlling the amount of NBS and the temperature. Elimination of methyl bromide from the monobrominated intermediates produces aromatic aldehydes, whereas hydrolysis of the dibrominated intermediates affords aromatic methyl esters in good yields.

Design, synthesis, anti-HIV activities, and metabolic stabilities of alkenyldiarylmethane (ADAM) non-nucleoside reverse transcriptase inhibitors.

The alkenyldiarylmethane (ADAM) HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) are effective anti-HIV agents in cell culture. However, the potential clinical utility of the ADAMs is expected to be limited by the presence of methyl ester moieties that are likely to be metabolized by nonspecific esterases in blood plasma to biologically inactive carboxylic acid derivatives. The present investigation was therefore undertaken to investigate the anti-HIV activities of the ADAMs versus HIV-1(IIIB) and HIV-2(ROD) in MT-4 cells and the stabilities of the biologically active ADAMs in rat plasma. The ADAMs displayed a wide range of metabolic stabilities in rat plasma, with half-lives ranging from 0.9 to 76.6 min. A wide assortment of structural modifications was tolerated, with 18 of the 32 compounds tested displaying EC(50) values between 0.3 and 3.7 microM versus HIV-1(IIIB) in MT-4 cells, 3 compounds in the EC(50) = 13.2-35.4 microM range, and the remaining compounds inactive. Consistent with the mechanism of action of the ADAMs as NNRTIs, they were inactive or displayed comparatively low activity versus HIV-2(ROD). The replacement of the two aromatic methyl ester substituents in one of the most active ADAMs (EC(50) = 0.6 microM) with two methyl thioester groups resulted in an increase in plasma half-life from 5.8 to 55.3 min, while maintaining the antiviral potency at the EC(50) = 1.8 microM level. At the same time, the bis(thioester) modification was less cytotoxic to uninfected MT-4 cells, with a CC(50) of >224 microM versus 160 microM for the parent compound.

Aromatic amino acid methyl ester analogs form quinonoidal species with Dopa decarboxylase

This study reports for the first time that binding of aromatic methyl ester analogs to Dopa decarboxylase in the native and inactive nicked forms causes the appearance of a dead-end quinonoidal species absorbing at 500 nm, in addition to an external aldimine absorbing at 398 nm. The equilibrium mixture of these species varies depending on both the analog structure and the enzyme form. The above mentioned intermediates are also characterized with respect to their CD properties and the equilibria for their formation are determined as a function of pH. The results have provided evidence that the establishment of proper contacts between the active site and hydroxyl groups of the ligand are indispensable in order to limit unwanted side reactions.