815-17-8Relevant articles and documents
Variation in pantothenate kinase type determines the pantothenamide mode of action and impacts on coenzyme A salvage biosynthesis
De Villiers, Marianne,Barnard, Leanne,Koekemoer, Lizb,Snoep, Jacky L.,Strauss, Erick
, p. 4731 - 4753 (2014)
N-substituted pantothenamides are analogues of pantothenic acid, the vitamin precursor of CoA, and constitute a class of well-studied bacterial growth inhibitors that show potential as new antibacterial agents. Previous studies have highlighted the importance of pantothenate kinase (PanK; EC 2.7.1.33) (the first enzyme of CoA biosynthesis) in mediating pantothenamide-induced growth inhibition by one of two proposed mechanisms: first, by acting on the pantothenamides as alternate substrates (allowing their conversion into CoA antimetabolites, with subsequent effects on CoA- and acyl carrier protein-dependent processes) or, second, by being directly inhibited by them (causing a reduction in CoA biosynthesis). In the present study we used structurally modified pantothenamides to probe whether PanKs interact with these compounds in the same manner. We show that the three distinct types of eubacterial PanKs that are known to exist (PanKI, PanKII and PanKIII) respond very differently and, consequently, are responsible for determining the pantothenamide mode of action in each case: although the promiscuous PanKI enzymes accept them as substrates, the highly selective PanKIIIs are resistant to their inhibitory effects. Most unexpectedly, Staphylococcus aureus PanK (the only known example of a bacterial PanKII) experiences uncompetitive inhibition in a manner that is described for the first time. In addition, we show that pantetheine, a CoA degradation product that closely resembles the pantothenamides, causes the same effect. This suggests that, in S. aureus, pantothenamides may act by usurping a previously unknown role of pantetheine in the regulation of CoA biosynthesis, and validates its PanK as a target for the development of new antistaphylococcal agents.
Novel synthesis method of metribuzin intermediate
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Paragraph 0015; 0017; 0019; 0021; 0023; 0025; 0027, (2020/01/25)
The invention discloses a novel synthesis method of a metribuzin intermediate, wherein the intermediate triazinone of metribuzin is produced by using pinacolone (methyl tert-butyl ketone) as an initial raw material through reaction steps of chlorination, hydrolysis, oxidation, condensation and the like. According to the invention, the reaction conditions are mild, and the total yield reaches 92.4%; hydrogen peroxide is used as an oxidizing agent for replacing sodium hypochlorite, and the oxidation reaction is carried out at a room temperature, so that the operation is convenient, and the byproduct is water so as to avoid the discharge of pollutants such as salt-containing wastewater and the like in the production process; and after the reaction is finished, the intermediate and the catalyst are subjected to chromatographic separation so as to recycle the water phase containing the catalyst.
Triazinone preparation method
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Paragraph 0037; 0038; 0042-0047, (2019/02/13)
The invention relates to a triazinone preparation method, which comprises: carrying out a hydrolysis reaction on 1-chloropinacolone at a temperature of 80-140 DEG C under the actions of a solvent andan alkali to obtain a compound I, wherein the solvent is water; carrying out an oxidation reaction on the compound I in the presence of oxygen by using Pt as a catalyst under a neutral or weakly basiccondition to obtain a compound II; and carrying out a ring closure reaction on the compound II and thiocarbohydrazide under the catalysis of an acid to obtain triazinone, wherein the structure formula of the compound I is defined in the specification, and the structure formula of the compound II is defined in the specification. According to the present invention, 1-chloropinacolone is used as theraw material, and the water is used as the solvent, such that the generation of high salt wastewater can be avoided; Pt is used as the catalyst, and oxygen is used as the oxidant, such that the use of hydrogen peroxide can be avoided, and the catalyst can be recycled so as to reduce the raw material cost; and the production method is simple, meets the environmentally friendly requirement, and issuitable for industrial production, and the yield and the content of the final product are high.