- The pyridine ring of NAD is formed by a nonenzymatic pericyclic reaction
-
The biosynthesis of quinolinate 3, the precursor to the pyridine ring of NAD, is still poorly understood. Two pathways have been identified, one involving the direct formation of quinolinic acid from aspartate and dihydroxyacetone phosphate, the other requiring a five-step degradation of tryptophan. The final step in this degradation is catalyzed by the non-heme Fe(II)-dependent enzyme 3-hydroxyanthranilate-3,4-dioxygenase (HAD). This enzyme catalyzes the oxidative ring opening of 3-hydroxyanthranilate (1) to 2-amino-3-carboxymuconic semialdehyde (ACMS, 2) which then cyclizes to quinolinate (3). In this communication, we demonstrate the following: (1) cyclization of ACMS to 3 is not HAD catalyzed, (2) the most stable form of ACMS in solution is an all trans isomer which undergoes facile cis to trans isomerization about the C2-C3 and C4-C5 double bonds via transient formation of its enol tautomer (6), (3) a model study on the ring opening of N,N-dimethylcarbamoylpyridinium with hydroxide and methoxide suggests that the cyclization of ACMS occurs by an electrocyclization reaction of its enol tautomer 6. Thus, the biosynthesis of quinolinic acid, by the tryptophan pathway, is likely to be a member of a growing family of natural products whose biosynthesis involves a pericyclic reaction. Copyright
- Colabroy, Keri L.,Begley, Tadhg P.
-
-
Read Online
- Preparation method of nitrogen-containing aromatic dicarboxylic acid
-
The invention discloses a preparation method of nitrogen-containing aromatic dicarboxylic acid. The method includes: taking quinoline, isoquinoline, benzimidazole or benzotriazole and a derivative thereof as the raw materials, adopting oxone as the oxidant, employing a metal salt as the catalyst and using inorganic acid as the medium, adding a phase transfer reagent, and carrying out reaction to obtain nitrogen-containing aromatic dicarboxylic acid. The reagents used by the method are high in stability, convenient for transportation and storage, the operation is simple, the conditions are easily controllable, and the price is low, at the same time, the catalytic effect is good, the yield is high, and waste liquid treatment is easy, therefore the method is convenient for industrial large-scale production.
- -
-
Paragraph 0022-0084; 0113-0124
(2020/03/02)
-
- Method for preparing nitrogen-containing six-membered ring dicarboxylic acid
-
The invention relates to compound preparation, particularly to a method for preparing nitrogen-containing six-membered ring dicarboxylic acid from a benzo nitrogen-containing six-membered ring compound. According to the method, a raw material compound and a sodium chlorate aqueous solution are catalyzed under an acidic condition to obtain nitrogen-containing six-membered ring dicarboxylic acid, wherein the raw material is a nitrogen-containing six-membered heterocyclic benzocyclic compound. According to the invention, the catalyst of the reaction system is low in toxicity and low in cost, no new impurity is generated in the post-treatment step, and large-scale production is facilitated.
- -
-
Paragraph 0033-0035; 0037
(2020/04/22)
-
- Observing 3-hydroxyanthranilate-3,4-dioxygenase in action through a crystalline lens
-
The synthesis of quinolinic acid from tryptophan is a critical step in the de novo biosynthesis of nicotinamide adenine dinucleotide (NAD+) in mammals. Herein, the nonheme iron-based 3-hydroxyanthranilate-3,4-dioxygenase responsible for quinolinic acid production was studied by performing time-resolved in crystallo reactions monitored by UV-vis microspectroscopy, electron paramagnetic resonance (EPR) spectroscopy, and X-ray crystallography. Seven catalytic intermediates were kinetically and structurally resolved in the crystalline state, and each accompanies protein conformational changes at the active site. Among them, a monooxygenated, seven-membered lactone intermediate as a monodentate ligand of the iron center at 1.59-? resolution was captured, which presumably corresponds to a substrate-based radical species observed by EPR using a slurry of small-sized single crystals. Other structural snapshots determined at around 2.0-? resolution include monodentate and subsequently bidentate coordinated substrate, superoxo, alkylperoxo, and two metal-bound enol tautomers of the unstable dioxygenase product. These results reveal a detailed stepwise O-atom transfer dioxygenase mechanism along with potential isomerization activity that fine-tunes product profiling and affects the production of quinolinic acid at a junction of the metabolic pathway.
- Wang, Yifan,Liu, Kathy Fange,Yang, Yu,Davis, Ian,Liu, Aimin
-
p. 19720 - 19730
(2020/09/18)
-
- A 2, 3 - pyridine dicarboxylic acid synthesis method
-
The invention discloses a 2, 3 - pyridine dicarboxylic acid synthesis method, CuSO4 · 5 H2 O, sulfuric acid, benzo pyridine sodium chlorate, to aldehyde benzoic acid methyl ester, pyrrole, H2 TCPP - OMe, MnCl2 · 6 H2 O as the main raw material, the synthesis process of the present invention benzo pyridine first NaClO in oxidation system3 - H2 SO4 - CuSO4 The catalyst under Mn - TCPP oxidation under the action of the open loop, after alkali hydrolysis, acidifying the resulting 2, 3 - pyridine dicarboxylic acid. For Mn - TCPP catalyst benzene ring and the double bond is connected to the electron-donative group, double bond can be increased on the electron cloud density, more easily reactant intermediate attack activation, therefore open-loop oxidation effect can be improved, so that the yield is obviously higher than the traditional potassium permanganate oxidation product yield.
- -
-
Paragraph 0009; 0010; 0011; 0012; 0013-0030
(2019/01/08)
-
- Dual Activity of Quinolinate Synthase: Triose Phosphate Isomerase and Dehydration Activities Play Together to Form Quinolinate
-
Quinolinate synthase (NadA) is an Fe4S4 cluster-containing dehydrating enzyme involved in the synthesis of quinolinic acid (QA), the universal precursor of the essential coenzyme nicotinamide adenine dinucleotide. The reaction catalyzed by NadA is not well understood, and two mechanisms have been proposed in the literature that differ in the nature of the molecule (DHAP or G-3P) that condenses with iminoaspartate (IA) to form QA. In this article, using biochemical approaches, we demonstrate that DHAP is the triose that condenses with IA to form QA. The capacity of NadA to use G-3P is due to its previously unknown triose phosphate isomerase activity.
- Reichmann, Debora,Couté, Yohann,Ollagnier De Choudens, Sandrine
-
p. 6443 - 6446
(2015/11/09)
-
- OZONOLYSIS OF AROMATICS AND/OR OLEFINS
-
The invention pertains to a process for oxidizing unsaturated starting materials, comprising: (i) providing a liquid composition containing an olefin and/or aromatic starting compound, (ii) compressing an ozone-containing gas to a pressure of at least 5 bar absolute, (iii) introducing the compressed ozone-containing gas in one or more microreactors, bringing said gas into contact with said liquid composition (i), to obtain an ozonide, (iv) and optionally subjecting said ozonide to oxidative or reductive degradation. The use of compressed ozone makes it possible to mix large gas volumes with small liquid volumes, and achieve satisfactory contact between the gas and liquid reactants. This dramatically improves yields over conventional micro-reactor-driven ozonolysis.
- -
-
Page/Page column 13-14
(2010/04/03)
-
- PROCESS FOR THE SAFE OZONOLYSIS OF ORGANIC COMPOUNDS IN FLAMMABLE SOLVENTS
-
An improved process for the safe ozonolysis of unsaturated, organic carbon compounds having one or more olefinic or aromatic double bonds in the molecule in flammable solvents for the preparation of mono- or biscarbonyl or hydroxy compounds, in which ozonolysis is carried out with the use of an ozone-carrying inert gas/O2 stream, in which the oxygen concentration in the inert gas/O2 stream is above the known limiting oxygen concentration of the homogeneous fuel/gas mixtures and below the safety-critical limiting oxygen concentration of the heterogeneous mixture of the liquid fuel and oxygen-containing gas which is dependent on the reaction conditions and at which ignition and flame propagation no longer take place.
- -
-
Page/Page column 22-23
(2008/12/06)
-
- Process for producing high-purity 2,3-pyridinedicarboxylic acid
-
A process for producing 2,3-pyridinedicarboxylic acid having a significantly decreased heavy metal content and capable of satisfying the purity level required for medicinal and agricultural chemicals comprising the steps of: adding at least one sulfur-containing substance selected from a hydrosulfide, a sulfide, a polysulfide, and sulfur to an aqueous solution of 2,3-pyridinedicarboxylic acid or its salt; removing the resulting precipitates from the solution; acidifying the solution with a mineral acid to precipitate 2,3-pyridinedicarboxylic acid; and recovering the precipitates. The aqueous solution to be treated may be an aqueous solution of an alkali metal salt of 2,3-pyridinedicarboxylic acid obtained by alkali decomposition of 2,3-pyridinedicarboxylic acid copper (II) salt, which has been formed or precipitated in a process for producing 2,3-pyridinedicarboxylic acid.
- -
-
Page/Page column 4; 5
(2008/06/13)
-
- Process for producing 2,3-pyridinedicarboxylic acid
-
Highly pure 2,3-pyridinedicarboxylic acid is produced by a process suitable for application in commercial production with a high yield and with recirculation of waste liquor. The process comprises the steps of: (a) oxidizing quinoline or 8-hydroxyquinoline in a solvent in the presence of copper (II) ions to precipitate copper (II) salt of 2,3-pyridinedicarboxylic acid and then separate the precipitates, (b) reacting the separated copper (II) salt with an alkali in a solvent to obtain a solution of an alkali metal salt of 2,3-pyridinedicarboxylic acid, and (c) reacting the solution of the alkali metal salt with a mineral acid to precipitate 2,3-pyridinedicarboxylic acid and then separate the precipitates, and is characterized in that (A) part or all of the solution obtained after the precipitated 2,3-pyridinedicarboxylic acid is separated in step (c) is used as at least part of the solvent in step (a) or (b), or (B) copper or a copper compound is added to the solution obtained after the precipitated 2,3-pyridine-dicarboxylic acid is separated in step (c) to recover the 2,3-pyridinedicarboxylic acid remaining in the solution as its copper (II) salt.
- -
-
Page/Page column 8-9
(2008/06/13)
-
- Compositions of matter having bioactive properties
-
Particles of coordinated complex comprising a basic, hydrous polymer and a capacitance adding compound, as well as methods for their production, are described. These complexes exhibit a high degree of bioactivity making them suitable for a broad range of applications through their incorporation into conventional vehicles benefiting from antimicrobial and similar properties.
- -
-
-
- Composition of matter having bioactive properties
-
Particles of coordinated complex comprising a basic, hydrous polymer and a capacitance adding compound, as well as methods for their production, are described. These complexes exhibit a high degree of bioactivity making them suitable for a broad range of applications through their incorporation into conventional vehicles benefiting from antimicrobial and similar properties.
- -
-
-
- Dexanabinol derivatives and their use as neuroprotective pharmaceutical compositions
-
PCT No. PCT/US95/01470 Sec. 371 Date Sep. 28, 1998 Sec. 102(e) Date Sep. 28, 1998 PCT Filed Feb. 6, 1995 PCT Pub. No. WO95/20958 PCT Pub. Date Aug. 10, 1995The present invention relates to pharmaceutical compositions for preventing or alleviating neurotoxicity. Said pharmaceutical compositions comprise as their active ingredient the stereospecific (+) enantiomers, having (3S,4S) configuration, of DELTA 6-tetrahydrocannabinol (THC) type compounds of general formula (I), as defined hereinbelow.
- -
-
-
- Aza analog of dithio-β-isoindigo
-
An improved synthesis of 2,3-pyridinedicarboxyic acid is proposed, providing a higher yield of the target product. The acid was used as starting material for the synthesis of dithio-β-isoindigo. The IR and electronic spectra of the latter were studied.
- Neustroeva
-
p. 1823 - 1826
(2007/10/03)
-
- Directed lithiation of unprotected pyridinecarboxylic acids
-
The lithium salts of 2-, 3- and 4-pyridinecarboxylic acids undergo deprotonation at the position adjacent to the carboxylate group when treated with LTMP in THF at 0 °C, -50 °C and -25 °C, respectively. The lithiation conditions could be extended to chlor
- Mongin, Florence,Trecourt, Francois,Queguiner, Guy
-
p. 5483 - 5486
(2007/10/03)
-
- Synthesis of 2-Aryl-2,3-dihydro-oxazolopyrrolopyridin-5-one and 2-Aryl-2,3-dihydro-oxazolopyrrolopyridin-5-one
-
A variety of 2-aryl-2,3-dihydro-oxazolopyrrolopyridin-5-one and 2-aryl-2,3-dihydro-oxazolopyrrolopyridin-5-one were prepared. The absolute configuration of the chiral centers were studied thoroughly from which the structural and stereoformulea of these compounds were deduced by using nmr and microanalysis technique.
- Makki, Mohamad S. I.,Samarkandy, Abdul-Rahim A.,Kabuli, Rida A.,Hewlins, M. J. E.
-
-
- Method for the sequential oxidation of substituted quinolines to produce substituted-pyridine-2,3-dicarboxylic acids
-
The present invention provides a novel process for the preparation of substituted pyridine--2,3-dicarboxylic acids by the sequential peroxide--hypochlorite oxidations of substituted quinolines.
- -
-
-
- Ozonolysis of Quinolines: A Versatile Synthesis of Polyfunctional Pyridines
-
A simple, safe and efficient procedure, easily adapted to a large scale, is described for the synthesis of substituted quinolines 2, which are readily oxidized by ozone in the presence of mineral acid, followed by an oxidative work up with hydrogen peroxide to afford substituted 2,3-pyridinedicarboxylic acids 3a-d,f and acyl pyridines 3e, g.
- O'Murchu, C.
-
p. 880 - 882
(2007/10/02)
-
- Process for the preparation of pyridine-2,3-dicarboxylic acid
-
Pyridine-2,3-dicarboxylic acid can be prepared by oxidizing quinoline with a chlorate salt in an aqueous acidic medium. The oxidation can be conducted in the presence of cupric ions generated from an acid-soluble cupric compound.
- -
-
-
- Pyridine derivatives and their herbicidal compositions
-
A pyridine derivative having the formula: STR1 wherein one of A, B, D and E is oxygen, sulfur, --SO--, --SO2 --, --NR3 --, STR2 or =CH-- with the rest being all carbon atoms; X is halogen, C1 -C4 alkyl, C1 -C4 alkoxy, C1 -C4 haloalkyl, C1 -C4 haloalkoxy, C1 -C4 alkylthio, C1 -C4 haloalkylthio, C1 -C4 alkoxycarbonyl, C1 -C4 alkylthioalkyl, tetrahydrothiopyranyl, hydroxyl, CF3, phenyl or pyridyl; n is an integer of from 0 to 6,; W is oxygen or sulfur; R is hydrogen, di-lower alkylimino, C1 -C5 alkyl, C2 -C5 alkenyl, C2 -C5 alkynyl, C4 or C5 oxacycloalkyl, C2 -C5 mono-, di- or tri-haloalkenyl, C2 -C5 haloalkynyl, glycidyl, furfuryl, alkylthioalkyl, C3 -C6 cycloalkyl or a cation R1 is C1 -C4 alkyl, R2 is C1 -C4 alkyl or C3 -C6 cycloalkyl, or R1 and R2 together with the ajacent carbon atom, form C3 -C6 cycloalkyl; and R3 is hydrogen or C1 -C3 alkyl. The compounds are used as herbicides.
- -
-
-
- Method for oxidizing alkyl groups on pyridine, quinoline and benzene ring compounds to carboxylic acids under basic conditions
-
There is provided a novel process for the preparation of carboxylic acids from alkyl groups under basic conditions utilizing oxides of copper, cobalt and silver.
- -
-
-
- Process for preparing quinolinic acid
-
This invention relates to improved processes for the manufacture of quinolinic acid run with a higher concentration of reactants in the initial step wherein quinoline is oxidized with hydrogen peroxide in an aqueous sulfuric acid solution in the presence of copper sulfate to prepare copper quinolinate, and in subsequent steps converting the copper quinolinate from the initial step to quinolinic acid by treating the copper salt with alkali to form the water soluble alkali salt form of quinolinic acid precipitating the copper as insoluble cupric oxide and thereafter treating the soluble alkali salt form with acid to obtain the quinolinic acid, the improvement whereby the reaction of the initial step is carried out in a thermally controllable and safe manner and the formation of by-products is minimized which comprises in the initial step adding separately either in portion-wise multiple and approximately equal portions or adding continuously and simultaneously over a period of time each of the following, the sulfuric acid, the quinoline and the hydrogen peroxide to an aqueous solution of the copper sulfate over such time intervals of sufficient length spaced between each group of portion-wise additions or at such a rate as to allow the hydrogen peroxide to react to maintain an unreacted hydrogen peroxide concentration in the reaction of between approximately three and approximately fifteen percent.
- -
-
-
- 1,1-Alkanediol dicarboxylate linked antibacterial agents
-
Useful antibacterial agents in which a penicillin and/or a beta-lactamase inhibitor are linked via 1,1-alkanediol dicarboxylates are of the formula STR1 where A is the residue of certain dicarboxyic acids, R3 is H or (C1 -C3), n is zero or 1 such that when n is zero R is P or B and R1 is the residue of certain esters, H or a salt thereof; and when n is 1, one of R and R1 is P and the other is B, and P is STR2 where R2 is H or certain acyl groups, and B is the residue of a beta-lactamase inhibiting carboxylic acid; a method for their use, pharmaceutical compositions thereof and intermediates useful in their production.
- -
-
-
- Mechanistic Aspects of Diazaquinone Chemiluminescence
-
Twelve cyclic hydrazides of aromatic and heterocyclic o-dicarboxylic acids were converted into diazaquinones by treatment with t-butyl hypochlorite.Chemiluminescence was produced from all diazaquinones on treatment with HO2- derived from hydrogen peroxide and potassium hydroxide.Diazaquinones derived from pyridine and pyrazine o-dicarboxylic acid hydrazides afforded chemiluminescence with hydrogen peroxide alone.Such nitrogen bases and N-oxides increase the nucleophilicity of hydrogen peroxide by complex formation and this effect was also exemplified by observation of chemiluminescence from phthalazine-1,4-diones, hydrogen peroxide and either pyridine or pyridine N-oxide.Highly reactive diazaquinones emit light with aqueous alkali and oxygen.No chemiluminescence was produced with organic bases and oxygen which suggests the involvement of a different mechanism compared with the hydroperoxide anion case.
- Paul, D. Brenton
-
p. 1001 - 1008
(2007/10/02)
-