Diethyl Oxaloacetate Research Articles

Synthesis and structural determination of some 1,5-disubstituted-4-ethoxycarbonyl-3-hydroxy-3-pyrroline-2-one derivatives containing nitro group

2-Pyrrolidinone is a γ-lactam heterocycle consisting of four carbon atoms and one nitrogen atom. In the family of 2-pyrrolidinone heterocycles, 3-pyrroline-2-ones, also named as 1,5-dihydro-2H-pyrrol-2-ones are important substructures of various natural products with promising biological activities. In addition, this γ-lactam heterocyclic ring also exists in synthetic medicinal compounds. In this manuscript, multi-component reactions (MCRs) were applied to synthesize three 1,5-disubstituted-4-ethoxycarbonyl-3-hydroxy-3-pyrroline-2-ones containing nitro group from aromatic aldehydes, 4-nitroaniline and sodium diethyl oxalacetate in absolute ethanol. Furthermore, the molecular structure of products has been proven via modern spectroscopic methods: nuclear magnetic resonance spectroscopy (1H NMR, 13C NMR) and electrospray ionization-high resolution mass spectrometry (ESI – HRMS).

An Efficient Method for the Programmed Synthesis of Multifunctional Diketopyrrolopyrroles

AbstractA new, transformative methodology for the preparation of diketopyrrolopyrroles from aldehydes, primary amines, nitriles, and diethyl oxalacetate has been developed. It is now possible to prepare diketopyrrolopyrroles bearing an ordered arrangement of three different substituents from abundant and commercially available materials, allowing the independent regulation of all desired physicochemical properties. For the first time very electron‐rich (carbazol‐3‐yl, dimethylaminophenyl, pyrrolo[3,2‐b]pyrrolyl), and sterically hindered substituents (naphthalen‐1‐yl, quinolin‐4‐yl, acridin‐9‐yl, imidazo[1,5‐a]pyridin‐1‐yl, 2‐bromophenyl etc.) can be appended to the diketopyrrolopyrrole core by condensation of an appropriate nitrile with a pyrrolidin‐2‐one intermediate. Even greater synthetic possibilities are related to the fact that such demanding substituents as 4‐dimethylaminophenyl, indol‐3‐yl, and 2‐methoxyphenyl can be incorporated from aldehyde precursors, bypassing problems with the nitriles reactivity.

An Efficient Method for the Programmed Synthesis of Multifunctional Diketopyrrolopyrroles.

A new, transformative methodology for the preparation of diketopyrrolopyrroles from aldehydes, primary amines, nitriles, and diethyl oxalacetate has been developed. It is now possible to prepare diketopyrrolopyrroles bearing an ordered arrangement of three different substituents from abundant and commercially available materials, allowing the independent regulation of all desired physicochemical properties. For the first time very electron-rich (carbazol-3-yl, dimethylaminophenyl, pyrrolo[3,2-b]pyrrolyl), and sterically hindered substituents (naphthalen-1-yl, quinolin-4-yl, acridin-9-yl, imidazo[1,5-a]pyridin-1-yl, 2-bromophenyl etc.) can be appended to the diketopyrrolopyrrole core by condensation of an appropriate nitrile with a pyrrolidin-2-one intermediate. Even greater synthetic possibilities are related to the fact that such demanding substituents as 4-dimethylaminophenyl, indol-3-yl, and 2-methoxyphenyl can be incorporated from aldehyde precursors, bypassing problems with the nitriles reactivity.

Evidence That Isoprene Emission Is Not Limited by Cytosolic Metabolites. Exogenous Malate Does Not Invert the Reverse Sensitivity of Isoprene Emission to High [CO2

Isoprene is synthesized via the chloroplastic 2-C-methyl-d-erythritol 4-phosphate/1-deoxy-d-xylulose 5-phosphate pathway (MEP/DOXP), and its synthesis is directly related to photosynthesis, except under high CO2 concentration, when the rate of photosynthesis increases but isoprene emission decreases. Suppression of MEP/DOXP pathway activity by high CO2 has been explained either by limited supply of the cytosolic substrate precursor, phosphoenolpyruvate (PEP), into chloroplast as the result of enhanced activity of cytosolic PEP carboxylase or by limited supply of energetic and reductive equivalents. We tested the PEP-limitation hypotheses by feeding leaves with the PEP carboxylase competitive inhibitors malate and diethyl oxalacetate (DOA) in the strong isoprene emitter hybrid aspen (Populus tremula × Populus tremuloides). Malate feeding resulted in the inhibition of net assimilation, photosynthetic electron transport, and isoprene emission rates, but DOA feeding did not affect any of these processes except at very high application concentrations. Both malate and DOA did not alter the sensitivity of isoprene emission to high CO2 concentration. Malate inhibition of isoprene emission was associated with enhanced chloroplastic reductive status that suppressed light reactions of photosynthesis, ultimately leading to reduced isoprene substrate dimethylallyl diphosphate pool size. Additional experiments with altered oxygen concentrations in conditions of feedback-limited and non-feedback-limited photosynthesis further indicated that changes in isoprene emission rate in control and malate-inhibited leaves were associated with changes in the share of ATP and reductive equivalent supply for isoprene synthesis. The results of this study collectively indicate that malate importantly controls the chloroplast reductive status and, thereby, affects isoprene emission, but they do not support the hypothesis that cytosolic metabolite availability alters the response of isoprene emission to changes in atmospheric composition.

Individual Amino Acid Supplementation Can Improve Energy Metabolism and Decrease ROS Production in Neuronal Cells Overexpressing Alpha-Synuclein.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by alpha-synuclein accumulation and loss of dopaminergic neurons in the substantia nigra (SN) region of the brain. Increased levels of alpha-synuclein have been shown to result in loss of mitochondrial electron transport chain complex I activity leading to increased reactive oxygen species (ROS) production. WT alpha-synuclein was stably overexpressed in human BE(2)-M17 neuroblastoma cells resulting in increased levels of an alpha-synuclein multimer, but no increase in alpha-synuclein monomer levels. Oxygen consumption was decreased by alpha-synuclein overexpression, but ATP levels did not decrease and ROS levels did not increase. Treatment with ferrous sulfate, a ROS generator, resulted in decreased oxygen consumption in both control and alpha-synuclein overexpressing cells. However, this treatment only decreased ATP levels and increased ROS production in the cells overexpressing alpha-synuclein. Similarly, paraquat, another ROS generator, decreased ATP levels in the alpha-synuclein overexpressing cells, but not in the control cells, further demonstrating how alpha-synuclein sensitized the cells to oxidative insult. Proteomic analysis yielded molecular insights into the cellular adaptations to alpha-synuclein overexpression, such as the increased abundance of many mitochondrial proteins. Many amino acids and citric acid cycle intermediates and their ester forms were individually supplemented to the cells with L-serine, L-proline, L-aspartate, or L-glutamine decreasing ROS production in oxidatively stressed alpha-synuclein overexpressing cells, while diethyl oxaloacetate or L-valine supplementation increased ATP levels. These results suggest that dietary supplementation with individual metabolites could yield bioenergetic improvements in PD patients to delay loss of dopaminergic neurons.

Diethyl oxalacetate sodium salt as a reagent to obtain functionalized spiro[indoline-3,4′-pyrano[2,3-c]pyrazoles

An efficient one-pot procedure for the synthesis of ethyl 6′-amino-5′-cyano-2-oxo-2′H-spiro[indoline-3,4′-pyrano[2,3-c]pyrazole]-3′-carboxylates in moderate to high yields is described.

Fumarate analogs act as allosteric inhibitors of the human mitochondrial NAD(P)+-dependent malic enzyme.

Human mitochondrial NAD(P)+-dependent malic enzyme (m-NAD(P)-ME) is allosterically activated by the four-carbon trans dicarboxylic acid, fumarate. Previous studies have suggested that the dicarboxylic acid in a trans conformation around the carbon-carbon double bond is required for the allosteric activation of the enzyme. In this paper, the allosteric effects of fumarate analogs on m-NAD(P)-ME are investigated. Two fumarate-insensitive mutants, m-NAD(P)-ME_R67A/R91A and m-NAD(P)-ME_K57S/E59N/K73E/D102S, as well as c-NADP-ME, were used as the negative controls. Among these analogs, mesaconate, trans-aconitate, monomethyl fumarate and monoethyl fumarate were allosteric activators of the enzyme, while oxaloacetate, diethyl oxalacetate, and dimethyl fumarate were found to be allosteric inhibitors of human m-NAD(P)-ME. The IC50 value for diethyl oxalacetate was approximately 2.5 mM. This paper suggests that the allosteric inhibitors may impede the conformational change from open form to closed form and therefore inhibit m-NAD(P)-ME enzyme activity.

ChemInform Abstract: An Efficient Synthesis of Poly‐Substituted Phenols and Pyridines from Morita—Baylis—Hillman Acetates and Diethyl Oxalacetate.

AbstractVarious phenol derivatives (III) synthesized by a one‐pot reaction of Morita—Baylis—Hillman acetates and sodium diethyl oxalacetate via a [4 + 2]‐cyclization.

Synthesis of pyrrolo[3,2-f]quinolines via reaction of 2,5-dimethyl- or 1,2,5-trimethyl-6-aminoindoles with β-ketoesters

The reaction of 2,5-dimethyl- or 1,2,5-trimethyl-6-aminoindoles with β-ketoesters (methyl and ethyl acetoacetates, diethyl oxaloacetate) was found to proceed chemoselectively via the interaction between an amino group of indole and the carbonyl function of ketoester, leading to the formation of enamines. In contrast to enamines synthesized from similar aminoindoles and β-diketones, enamines obtained from β-ketoesters can easily undergo thermal cyclization, furnishing pyrrolo[3,2-f]quinolines with an angular catenation of rings.

An Efficient Synthesis of Poly-Substituted Phenols and Pyridines from Morita-Baylis-Hillman Acetates and Diethyl Oxalacetate

E-mail: kimjn@chonnam.ac.krReceived June 27, 2013, Accepted July 22, 2013Various phenol derivatives were synthesized in a one-pot reaction from MBH acetates and sodium diethyloxalacetate via a [4C+2C] cyclization protocol. In addition, some pyridine derivatives could also besynthesized using the same starting materials, by isolating the S

Biochemical and biophysical characterization of succinate: Quinone reductase from Thermus thermophilus

Enzymes serving as respiratory complex II belong to the succinate:quinone oxidoreductases superfamily that comprises succinate:quinone reductases (SQRs) and quinol:fumarate reductases. The SQR from the extreme thermophile Thermus thermophilus has been isolated, identified and purified to homogeneity. It consists of four polypeptides with apparent molecular masses of 64, 27, 14 and 15 kDa, corresponding to SdhA (flavoprotein), SdhB (iron–sulfur protein), SdhC and SdhD (membrane anchor proteins), respectively. The existence of [2Fe–2S], [4Fe–4S] and [3Fe–4S] iron–sulfur clusters within the purified protein was confirmed by electron paramagnetic resonance spectroscopy which also revealed a previously unnoticed influence of the substrate on the signal corresponding to the [2Fe–2S] cluster. The enzyme contains two heme b cofactors of reduction midpoint potentials of −20 mV and −160 mV for b H and b L, respectively. Circular dichroism and blue-native polyacrylamide gel electrophoresis revealed that the enzyme forms a trimer with a predominantly helical fold. The optimum temperature for succinate dehydrogenase activity is 70 °C, which is in agreement with the optimum growth temperature of T. thermophilus. Inhibition studies confirmed sensitivity of the enzyme to the classical inhibitors of the active site, as there are sodium malonate, sodium diethyl oxaloacetate and 3-nitropropionic acid. Activity measurements in the presence of the semiquinone analog, nonyl-4-hydroxyquinoline-N-oxide (NQNO) showed that the membrane part of the enzyme is functionally connected to the active site. Steady-state kinetic measurements showed that the enzyme displays standard Michaelis–Menten kinetics at a low temperature (30 °C) with a K M for succinate of 0.21 mM but exhibits deviation from it at a higher temperature (70 °C). This is the first example of complex II with such a kinetic behavior suggesting positive cooperativity with k' of 0.39 mM and Hill coefficient of 2.105. While the crystal structures of several SQORs are already available, no crystal structure of type A SQOR has been elucidated to date. Here we present for the first time a detailed biophysical and biochemical study of type A SQOR—a significant step towards understanding its structure–function relationship.

ChemInform Abstract: A Biocatalytic Approach to the Enantioselective Synthesis of (R)- and ( S)-Malic Acid.

(S)-Diethyl malate 1a was prepared (70–80% yield; > 98% optical purity) by an enantioselective reduction of sodium diethyl oxalacetate 2 by fermenting baker's yeast (Saccharomyces cerevisiae). Other microorganisms were tested for their capability of reducing 2. Most of them afforded (S)-1a-with ee from 8 to 94% and only Candida utilis, Aspergillus niger and Lactobacillus fermentum ILC G18D preferentially reduced compound 2 to (R)-1a. (R)-Dimethyl malate 1b was obtained from (R,S)-malate 1b by hydrolysis with pig liver esterase (PLE), the highest ee (93%) being realized at 0 °C in 20% aqueous methanol. Enzymatic hydrolyses of protected malates 1d and 1e did not lead to improvement of the ee.

ChemInform Abstract: Synthesis and Application of Ethyl 3-(4-Dialkylaminophenyl)-2-(quinoxalin-3(4H)-on-2-yl)propenoates and Related Products.

Ethyl quinoxalin-3(4H)-on-2-ylacetate was prepared by the condensation of 1,2-diaminobenzene and diethyl oxalacetate (sodium salt). The key quinoxaline intermediate was condensed with a variety of 4-dialkylaminobenzaldehydes/substituted benzaldehydes to yield novel brilliant quinoxalin-2-yl styryl dyes which were applied on polyester fibers as disperse dyes and their dyeing properties were studied.

Synthesis of Substituted Pyrrolo[3,2‐f]quinolines (IV) from 5‐Aminoindoles (I) and Diethyl Oxaloacetate.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Synthesis of substituted pyrrolo[3,2-f]-quinolines from 5-aminoindoles and diethyl oxaloacetate

The reactions of a series of substituted 5-aminoindoles with diethyl oxaloacetate were studied. A synthesis was developed for 5-indolylamino derivatives of diethyl fumarate as well as 7-ethoxycarbonyl-6,9-dihydro-3H-pyrrolo[3,2-f]quinolin-9-ones.

New Triazinoindoles Through the Action of 3‐Hydrazino[1,2,4]triazino[5,6‐b]indole on α,β‐Unsaturated Compounds.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis and application of ethyl 3-(4-dialkylaminophenyl)-2-(quinoxalin-3(4H)-on-2-yl)propenoates and related products

Ethyl quinoxalin-3(4H)-on-2-ylacetate was prepared by the condensation of 1,2-diaminobenzene and diethyl oxalacetate (sodium salt). The key quinoxaline intermediate was condensed with a variety of 4-dialkylaminobenzaldehydes/substituted benzaldehydes to yield novel brilliant quinoxalin-2-yl styryl dyes which were applied on polyester fibers as disperse dyes and their dyeing properties were studied.

Synthesis and some reactions of 1,2-diamino-1,3-diaza- and 1,2-diamino-1-azaazulenium salts

Amination of azaazulenes 1–3 with O-mesitylsulfonylhydroxylamine occurs at N-1 and gives the corresponding azaazulenium salts 4–6. The treatment of the salts 4 and 6 with potassium carbonate gives 1-amino-2-imino-1,2-dihydro-1,3-diaza- and 1-azaazulenes. The structure of 1-amino-2-ethylimino-1,2-dihydro-1-azaazulene (10) was characterized by X-ray crystal structure analysis. Reaction of the salt 4 with acetic anhydride gave 2-methyl-1,3,3a,9-tetraazacyclopent[a]azulene. The reaction of the salts 4 and 5 with diethyl ethoxymethylenedicarboxylate (DEEM) in the presence of potassium carbonate in acetonitrile gave 1,3,3a,9-tetraaza- (19) and 1,3,3a-triazacyclopent[a]azulene derivatives (21) as major products, whereas the reaction in ethanol gave 1,2a,3-triaza- (17) and 2a,3-diazabenz[cd]azulene derivatives (22), respectively. Similar treatment of 6 with DEEM gave diethyl (2-ethylimino-1,2-dihydro-1-azaazulen-1-yl)aminomethylenemalonate 23, which converted to 2a,3-diazabenz[cd]azulene derivative (24). The salts 4–6 reacted with active methylene compounds such as diethyl acetonedicarboxylate, diethyl oxalacetate and ethyl pyruvate, at the N-amino group followed by a cyclization at the C-8 position on the azaazulene ring to give 1,2a,3-triaza- (25, 28, 29) and 2a,3-diazabenz[cd]azulene derivatives (26, 27, 30). Cycloaddition of the salts 4–6 with acetylenic esters in the presence of potassium carbonate proceeded regioselectively and gave 1,2a,3-triaza- (32–35) or 2a,3-diazabenz[cd]azulene derivatives (31, 36, 37, 39–41).

Regulation and Localization of Key Enzymes during the Induction of Kranz-Less, C4-Type Photosynthesis in Hydrilla verticillata.

Kranz-less, C4-type photosynthesis was induced in the submersed monocot Hydrilla verticillata (L.f.) Royle. During a 12-d induction period the CO2 compensation point and O2 inhibition of photosynthesis declined linearly. Phosphoenolpyruvate carboxylase (PEPC) activity increased 16-fold, with the major increase occurring within 3 d. Asparagine and alanine aminotransferases were also induced rapidly. Pyruvate orthophosphate dikinase (PPDK) and NADP-malic enzyme (ME) activities increased 10-fold but slowly over 15 d. Total ribulose-1,5-bisphosphate carboxylase/oxygenase activity did not increase, and its activation declined from 82 to 50%. Western blots for PEPC, PPDK, and NADP-ME indicated that increased protein levels were involved in their induction. The H. verticillata NADP-ME polypeptide was larger (90 kD) than the maize C4 enzyme (62 kD). PEPC and PPDK exhibited up-regulation in the light. Subcellular fractionation of C4-type leaves showed that PEPC was cytosolic, whereas PPDK and NADP-ME were located in the chloroplasts. The O2 inhibition of photosynthesis was doubled when C4-type but not C3-type leaves were exposed to diethyl oxalacetate, a PEPC inhibitor. The data are consistent with a C4-cycle concentrating CO2 in H. verticillata chloroplasts and indicate that Kranz anatomy is not obligatory for C4-type photosynthesis. H. verticillata predates modern terrestrial C4 monocots; therefore, this inducible CO2-concentrating mechanism may represent an ancient form of C4 photosynthesis.

Chemoenzymatische Synthese von13C-markierter S-(-)-�pfels�ure

Chemoenzymatic Synthesis of 13C-Labeled S-(-)-Malic Acid The first regio- and stereospecific synthesis of S-(-)-13C-malic acid 5 with a high incorporation of 13C and excellent enantiomeric excess is described. S-(-)-13C-malic acid 5 was synthesized in a three-step reaction starting with ethyl acetate 2 and diethyl oxalate 1. The produced sodium diethyl oxaloacetate 3 was then enantioselectively reduced with bakers' yeast to S-(-)-13C-malic acid diethylester 4 which was hydrolyzed to S-(-)-13C-malic acid 5.