Methyl Ester Derivatives Research Articles

The Reaction of N-Trimethylsilyl-Substituted Heteroarylamines with Esters and Thioesters: An Efficient Protocol To Access Diheteroarylamides

The S-benzyl thioester and methyl ester derivatives of a representative 4-pyridinone-based carboxylic acid were sufficiently activated to react efficiently in amide coupling reactions with the amide anion generated in situ from the N-trimethylsilyl derivative of different weakly nucleophilic heteroarylamines. In acetonitrile as solvent, the precipitated diheteroarylamide products were isolated in pure form by vacuum filtration. This simple amide bond forming protocol can be readily adapted to the parallel synthesis of compound libraries.

A Crystallization-Induced Asymmetric Transformation using Racemic Phenyl Alanine Methyl Ester Derivatives as Versatile Precursors to Prepare Amino Acids

L-Tyrosine and L-Dopa are the precursors in the biological synthesis of amine neurotransmitters. On the other hand, phenylalanine as an aromatic amino acid (AAA) is a precursor in the synthesis of L-Tyrosine and L-Dopa. For some substrates such as amino acids, resolution by the formation of diastereomers offers an attractive alternative. Among different methods in this case, crystallization-induced asymmetric transformation (CIAT) that is in situ racemization and selective crystallization of a reaction product can be a good choice. Using this method, preparation of L-Tyrosine and L-Dopa has been reported. In the synthetic route, racemic phenyl alanine methyl ester derivatives as versatile precursors were prepared by reducing azlactone derivatives with Mg in methanol as a reducing reagent and then in the resolution step (S)- enantiomer of L-Dopa (3,4-dihydroxyphenylalanine) and L-Tyrosine (4-hydroxyphenylalanine) were achieved via salt formation with (2R,3R)-tartaric acid in the presence of 5-nitro salicylaldehyde in good yield and high optical purity.

Large-volume injection gas chromatography-vacuum ultraviolet spectroscopy for the qualitative and quantitative analysis of fatty acids in blood plasma

Qualitative and quantitative determination of fatty acids in plasma is of extreme importance as these are indicators of metabolic diseases. In this work, a sensitive and rugged method for detecting and quantifying fatty acids (as fatty acid methyl ester derivatives, FAMEs) in blood plasma was developed. The use of large-volume injection (LVI) gas chromatography-vacuum ultraviolet spectroscopy (GC-VUV) for analysis of fatty acids in blood plasma allowed the injection of higher sample volumes to accommodate sufficient analyte on-column for necessary detection ranges with a run time of 45 min. Calibration curves exhibited consistent linearity and reproducibility and were used along with internal standards for the quantification of 11 saturated and 21 unsaturated fatty acids. Intra-day and inter-day (n = 6) CVs had an average of 5 and 6%, respectively, and recoveries an average of 105%. The concentrations of EPA, DHA, and AA, as well as the omega-3 index and omega-6/omega-3 ratio, were calculated and compared with clinically actionable measurement ranges. Due to the use of LVI, the more volatile analyte (C8:0) was lost and therefore impossible to quantify. The volatility cutoff was determined to be the C10:0 analyte with a molecular weight of 186.295 g/mol.

GC-MS analysis of antibacterial compounds from floral part of methanolic extract of Rosa damascene

Abstract The present study was carried out with the aim to evaluate the bioactive constituent in Rosa damascena, which is commonly called Demask rose, medicinal plant with biological significance and belongs to Rosaceae. The analyses were performed in methanolic extract with two fraction, Butanol and ethyl acetate. The analysis reveals presence of 09 bioactive compounds. Out of nine compounds, five were derivatives of methyl ester. Chemical compounds found in selected plants possessMethanolic extract of plant in butanol and ethyl acetate fraction are found to possess significant potential to kill different bacterial species such as Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Proteus mirabillis. All these bacterial species were isolated from different sources such as pus, urine, vaginal sweat and sputum. Extract of Rosa damascena was able to kill all above mentioned species but was not capable to destroy Klebsiella oxytoca isolated from urine. Keywords: Bioactive compounds; GC-MS hyphenated technique; in-vitro Antibacterial assay; Medicinal plants; Rosa damascena http://dx.doi.org/10.19045/bspab.2018.700206

Synthesis of 2-Cyanoethoxy and 2-(1H-Tetrazol-5-yl)ethoxy Derivatives of Glycyrrhetic Acid Methyl Ester

Cyanoethylation of natural glycyrrhetic acid methyl ester gave the corresponding 3β-O-(2-cyanoethyl) derivative which was treated with sodium azide to obtain a novel tetrazolyl derivative of biologically active triterpenoid, methyl 3β-[2-(1H-tetrazol-5-yl)ethoxy]-11-oxoolean-12-en-30-oate.

Study of oxidation behavior of Jatropha oil methyl esters and Karanja oil methyl esters blends with EURO-IV high speed diesel

Poor oxidation stability of methyl esters is the major problem associated with its worldwide acceptance. As per the standards EN 14214 and prEN16091; and ASTM-D 7545-09 the oxidation stability limit should be 20 h for the blends and 8 h for neat methyl ester. One approach for increasing resistance of fatty acid methyl ester derivatives against autoxidation is to treat them with oxidation inhibitors known as antioxidants. This study examines the effectiveness of five such commercial antioxidants [viz. tert-butylhydroquinone (TBHQ), butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), propyl gallate (PrG) and pyrogallol (PY)] on the storage stability of Jatropha methyl ester (JOME), Karanja methyl ester (KOME), and their 5%, 10%, 20% and 40% blends with low sulphur EURO-IV High speed Diesel (HSD) using Petrotest PetrOxymeter. The impact of the antioxidants strongly depends on the feed-stock used for biodiesel production. PY was found to be the most effective antioxidant for JOME and its EURO-IV blends; however, PrG has shown maximum effectiveness with KOME and its EURO-IV HSD blends. 500 ppm was found to be the most optimum concentration for both the antioxidants.

Synthesis of β-Lactam and Anomalous Minor Products in the (i-Pr)2NEt-Promoted Reaction of N-Chloroglycine Methyl Ester Derivative with Dichloroacetyl Chloride

Apart from the expected [2 + 2]-cycloaddition product, the reaction of N-chloro-N-(2-methoxy-2-oxoethyl)-β-alanine methyl ester with dichloroacetyl chloride in the presence of ethyl(diisopropyl)amine gave minor N-(1,2-dichloro-2-oxoethyl)-β-alanine methyl ester and (3E)-1,1,1-trichloro-4-(diisopropylamino)- but-3-en-2-one.

Molecular Dynamics Simulation of Cyclooxygenase-2 Complexes with Indomethacin closo-Carborane Analogs.

Molecular dynamics simulation of carborane-containing ligands in complex with target enzymes is a challenging task due to the unique structure and properties of the carborane substituents and relative lack of appropriate experimental data to help assess the quality of carborane force field parameters. Here, we report results from energy minimization calculations for a series of carborane-amino acid complexes using carborane force field parameters published previously in the literature and adapted for use with the AMBER ff99SB and ff14SB potential functions. These molecular mechanics results agree well with quantum mechanical geometry optimization calculations obtained using dispersion-corrected density functional theory methods, suggesting that the carborane force field parameters should be suitable for more detailed calculations. We then performed molecular dynamics simulations for the 1,2-, 1,7-, and 1,12-dicarba- closo-dodecaborane(12) derivatives of indomethacin methyl ester bound with cyclooxygenase-2. The simulation results suggest that only the ortho-carborane derivative forms a stable complex, in agreement with experimental findings, and provide insight into the possible molecular basis for isomer binding selectivity.

Unprecedented Stereocontrol in the Synthesis of 1,2,3‐Trisubstituted Tetrahydro‐β‐carbolines through an Asymmetric Pictet–Spengler Reaction towards Sarpagine‐Type Indole Alkaloids

The asymmetric Pictet–Spengler (P‐S) reaction of chiral Nb‐ethynyl‐substituted tryptophan methyl ester derivatives (from both d‐ and l‐tryptophan) with a simple aliphatic aldehyde, exhibited unprecedented selectivity towards either of the diastereomeric products. A simple variation of conditions could alter the outcome of the cyclization from either 100 % trans‐selective to 100 % cis‐selective originating entirely from internal asymmetric induction under mild conditions. This resulted in a highly efficient access to both 1,3‐cis‐(1,2,3‐trisubstituted tetrahydro‐β‐carbolines, THβCs) and 1,3‐trans‐(1,2,3‐trisubstituted THβCs). To the best of our knowledge, this type of stereocontrol has never been observed from tryptophan methyl ester derivatives (either D or L) in accessing either 1,3‐disubstituted or 1,2,3‐trisubstituted THβCs. By exploiting this very useful ambidextrous diastereoselectivity, we have set the crucial C‐3 and C‐5 stereocenters of C‐19 methyl‐substituted sarpagine/macroline/ajmaline alkaloids beginning with the DNA‐encoded and cheaper l‐(–)‐tryptophan, as well as optionally from commercially available d‐(+)‐tryptophan.

One-pot synthesis of triazines as potential agents affecting cell differentiation

This paper outlines the synthesis of a number of structural analogs of 3-[(4,6-diphenoxy-1,3,5-triazin-2-yl)amino]benzoic acid which represent compounds with potential cardiogenetic activity. A one-pot protocol was developed for swift functionalization of the 1,3,5-triazine core without the need of isolating intermediates. The developed route starts from readily available 2,4,6-trichloro-1,3,5-triazine, displacing the chlorine atoms sequentially by aryloxy, arylamino, or arylthio moieties to enable access to molecules with three different substituents of this type in good yields. To facilitate purification, tert-butyl, methyl, and ethyl ester derivatives of the target compounds were initially synthesized. The tert-butyl esters could be readily hydrolyzed to the desired compounds, while reduction of the methyl and ethyl esters gave the corresponding benzylic alcohols in high yields, thereby expanding the substrate scope for future relevant cell assays.Graphical abstract

Enantioselective Synthesis of Thailanstatin A Methyl Ester and Evaluation of in Vitro Splicing Inhibition.

Thailanstatin A has been isolated recently from the fermentation broth of B. thailandensis MSMB43. We describe here an enantioselective convergent synthesis of thailanstatin A methyl ester and evaluation of its splicing activity. Synthesis of both highly functionalized tetrahydropyran rings were carried out from commercially available tri- O-acetyl-d-glucal as the key starting material. Our convergent synthesis involved the synthesis of both tetrahydropyran fragments in a highly stereoselective manner. The fragments were then coupled using cross-metathesis as the key step. The synthesis of the diene subunit included a highly stereoselective Claisen rearrangement, a Cu(I)-mediated conjugate addition of MeLi to set the C-14 methyl stereochemistry, a reductive amination reaction to install the C16-amine functionality, and a Wittig olefination reaction to incorporate the diene unit. The epoxy alcohol subunit was synthesized by a highly selective anomeric allylation, a Peterson olefination, and a vanadium catalyzed epoxidation that installed the epoxide stereoselectively. Cross-metathesis of the olefins provided the methyl ester derivative of thailanstatin A. We have carried out in vitro splicing studies of the methyl ester derivative, which proved to be a potent inhibitor of the spliceosome.

Synthesis of cis- and trans-(±)-3-mercaptoproline and pipecolic acid derivatives via thio-Michael addition

The reactivity of 2,3-dehydroproline and 2,3-dehydropipecolic acid methyl ester derivatives with S-nucleophiles in the thio-Michael addition reaction has been explored. The addition of triphenylmethanethiol and subsequent trityl cleavage led to the corresponding cis- and trans-(±)-3-mercaptoproline and pipecolic acid derivatives in good yields.

Stereospecific Formation of Z-Trisubstituted Double Bonds by the Successive Action of Ketoreductase and Dehydratase Domains from trans-AT Polyketide Synthases.

Incubation of (±)-2-methyl-3-ketobutyryl-SNAC (3) and (±)-2-methyl-3-ketopentanoyl-SNAC (4) with BonKR2 or OxaKR5, ketoreductase domains from the bongkrekic acid (1) and oxazolomycin (2) polyketide synthases, in the presence of NADPH gave in each case the corresponding (2 R,3 S)-2-methyl-3-hydroxybutyryl-SNAC (5) or (2 R,3 S)-2-methyl-3-hydroxypentanoyl-SNAC (6) products, as established by chiral gas chromatography-mass spectrometry analysis of the derived methyl esters. Identical results were obtained by BonKR2- and OxaKR5-catalyzed reduction of chemoenzymatically prepared (2 R)-2-methyl-3-ketopentanoyl-EryACP6, (2 R)-2-methyl-3-ketobutyryl-BonACP2 (12), and (2 R)-2-methyl-3-ketopentanoyl-BonACP2 (13). The paired dehydratase domains, BonDH2 and OxaDH5, were then shown to catalyze the reversible syn dehydration of (2 R,3 S)-2-methyl-3-hydroxybutyryl-BonACP2 (14) to give the corresponding trisubstituted ( Z)-2-methylbutenoyl-BonACP2 (16).

An Analytical Simplification for Faster Determination of Fatty Acid Composition and Phytosterols in Seed Oils

The fatty acid composition and the amounts of individual and total sterols in vegetable oils are the main analyses applied in the food industry to establish the oil nature. While the fatty acid composition is a relatively simple, fast analysis, the determination of phytosterols requires a laborious and time-consuming sample preparation. Both methods require a relatively large amount of oil, which may be an important drawback when only small samples are available. In this study, an analytical procedure that combines the sample preparation of both determinations is proposed to analyze small amounts of seed oils. From a single sample preparation, the total analysis time was considerably shortened. By applying a total methylation, the triacylglycerols and free fatty acids were transformed into fatty acid methyl ester (FAME) derivatives. Likewise, free sterols were completely released from their conjugated forms. Then, the derivatized oil was fractionated by solid-phase extraction into two fractions containing the FAME and free sterols, respectively. Both fractions were analyzed by gas-liquid chromatography. The analytical changes introduced provided reliable results for the main fatty acids and the major sterols in terms of accuracy and repeatability. Compared to the standard procedures, the time for sample preparation was reduced by half. In addition, it was much less laborious and required less volume of organic solvents, which reduced considerably the total cost of analysis and solvent waste. Consequently, the method proposed can be adopted as routine analysis in laboratories of oil quality control in the food industry.

Engineering of Solvatomorphs of the Luminescent Complex of ortho-Phenylenediboronic Acid and 8-Hydroxyquinoline

ortho-Phenylenediboronic acid reacts efficiently with 8-hydroxyquinoline yielding a luminescent yellowish complex soluble in a number of typical organic solvents. Through a solvent-evaporation method, five solvatomorphs and one structure of an ester of the studied compound were crystallized. Four of the solid-state forms (i.e., crystals containing acetone, tetrahydrofuran (THF), 1,4-dioxane, and acetonitrile) are isostructural, whereas the presence of dichloromethane leads to a different crystal structure. In turn, methanol, instead of being incorporated into the structural voids, reacts with the complex molecule which results in a methyl ester derivative. All crystals were characterized by X-ray diffraction, differential scanning calorimetry, theoretical computations, and solid-state time-resolved spectroscopy. Acetone and THF are located at the center of symmetry and are disordered, while symmetric dioxane fits perfectly into such structural voids, which enhances the crystal quality. It is reflected in ...

Profiling of Sulfate-Reducing Bacteria in an Offshore Oil Reservoir Using Phospholipid Fatty Acid (PLFA) Biomarkers

PLFA analysis was conducted to profile microorganisms and trace sulfate-reducing bacteria (SRB) in water samples from an offshore oil reservoir. From the results of spiked phospholipid standards, more than 90% of the phospholipids were recovered before the treatment of fatty acid methyl ester (FAME) derivatization while the relative standard deviations (RSD) were below 8.0%. The water samples from the injection well and four producing wells exhibited various reducing conditions and were further subjected to PLFA analysis. Fourteen kinds of phospholipid fatty acids were detected in the five wellbores and the concentrations of total fatty acids ranged from 368.4 to 3468.9 ng/L. Possible SRB biomarkers and significant phospholipid fatty acids associated with SRB including C14:0, i-C15:0, a-C15:0, C15:0, C16:1 (cis-9), C17:0, C18:1 (cis-9), C18:1 (cis-11) and C18:0 were selected for determining the presence of SRB species and evaluating the sulfate-related microbial biomass. The possible existence of SRB genera Desulfobacter, Desulfotomaculum, Desulfovibrio, and sulfur-oxidizing bacteria (SOB) in the reservoir were proposed based on PLFA profiles. The highest biomass was found in the most reducing well where very limited SOB biomarkers were found. Results indicated that the presence of SRB and SOB species was closely associated with the redox environment of the reservoir wellbores. The species distribution patterns were interpreted to elucidate the biological souring process.

Molecular Modeling of the Interactions between Carborane-Containing Analogs of Indomethacin and Cyclooxygenase-2.

Molecular modeling studies were performed in order to gain insight into the binding mode and interaction of carborane-containing derivatives of indomethacin methyl ester with the cyclooxygenase-2 (COX-2) isoform, and to assess the predictive capability of the computational tools available for studying carboranes, a unique class of pharmacophores. Docking simulations were able to identify the correct binding mode and reproduced the experimental binding affinity trends with encouraging quality. Nevertheless, the docking results needed to be verified through extensive and resource-intensive quantum chemical calculations, and the interpretation of the theoretical results would not have been straightforward without the supporting experimental data. The inclusion of full receptor and ligand flexibility into the molecular modeling of carborane-containing drug molecules may yield more definitive results, but is currently hindered by the lack of appropriate carborane force field parameters.

Synthesis and antimicrobial activity of 6-sulfo-6-deoxy-D-glucosamine and its derivatives

6-Sulfo-6-deoxy-D-glucosamine (GlcN6S), 6-sulfo-6-deoxy-D-glucosaminitol (ADGS) and their N-acetyl and methyl ester derivatives have been synthesized and tested as inhibitors of enzymes catalyzing reactions of the UDP-GlcNAc pathway in bacteria and yeasts. GlcN6S and ADGS at micromolar concentrations inhibited glucosamine-6-phosphate (GlcN6P) synthase of microbial origin. The former was also inhibitory towards fungal GlcN6P N-acetyl transferase, but at millimolar concentrations. Both compounds and their N-acetyl derivatives exhibited antimicrobial in vitro activity, with MICs in the 0.125–2.0 mg mL−1 range. Antibacterial but not antifungal activity of GlcN6S was potentiated by D-glucosamine and a synergistic antibacterial effect was observed for combination of ADGP and a dipeptide Nva-FMDP.

Derivatization and Gas Chromatography of Fatty Acids from Yeast.

Analysis of fatty acids by gas chromatography (GC) is facilitated by the generation of volatile fatty acid methyl ester (FAME) derivatives. Here we describe the esterification procedure and a typical program for separating FAMEs using a gas chromatograph equipped with a flame ionization detector or a dual stage quadrupole-mass spectrometry detector. GC is a rather simple technique that provides quantitative information on cellular fatty acid content and composition by use of an internal fatty acid standard.

Chemoenzymatic Preparation of Enantiomerically Enriched (R)‐(–)‐Mandelic Acid Derivatives: Application in the Synthesis of the Active Agent Pemoline

The enantioselective resolution of several racemic derivatives of mandelic acid methyl ester catalyzed by lipases from Pseudomonas fluorescens (Amano AK) or Burkholderia cepacia (Amano PS‐C II and Amano PS‐IM) has been achieved. A gram‐scale lipase‐mediated kinetic resolution approach has been developed that allows the facile synthesis of the corresponding methyl (R)‐(–)‐mandelates with excellent enantiomeric excesses (up to >99 % ee) and reaction enantioselectivity (E values up to >200). The dopaminergic agent pemoline, used in the treatment of attention‐deficit hyperactivity disorder (ADHD) and narcolepsy, was synthesized with 98 % ee in a straightforward route by condensing the prepared methyl (R)‐(–)‐mandelate with guanidine hydrochloride under basic conditions. The desired (R)‐(+)‐pemoline in optically pure form (>99 % ee) was obtained after two recrystallizations from ethanol. However, it was confirmed by chiral HPLC that optically active pemoline undergoes racemization in methanol solution.