89-00-9Relevant articles and documents
The pyridine ring of NAD is formed by a nonenzymatic pericyclic reaction
Colabroy, Keri L.,Begley, Tadhg P.
, p. 840 - 841 (2005)
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
Observing 3-hydroxyanthranilate-3,4-dioxygenase in action through a crystalline lens
Wang, Yifan,Liu, Kathy Fange,Yang, Yu,Davis, Ian,Liu, Aimin
, p. 19720 - 19730 (2020/09/18)
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.
A 2, 3 - pyridine dicarboxylic acid synthesis method
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Paragraph 0009; 0010; 0011; 0012; 0013-0030, (2019/01/08)
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.