- Adsorbent-Based Downstream-Processing of the Decarboxylase-Based Synthesis of 2,6-Dihydroxy-4-methylbenzoic Acid
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In this case study the regioselective enzymatic carboxylation of 3,5-dihydroxytoluene (orcinol) using the nonoxidative 2,3-dihydroxybenzoic acid decarboxylase from Aspergillus oryzae (2,3-DHBD-Ao), followed by an adsorbent-based downstream approach, has been investigated. The product 2,6-dihydroxy-4-methylbenzoic acid (DHMBA) was herein purified by an adsorption-desorption cycle and subsequently obtained with purities >99% without a full elimination of the excess bicarbonate from its reaction solution. Ten adsorbent resins were studied in respect of their ability to recover the product from the reaction solution, whereas the strong anion exchange resin Dowex 1x2 in its chloride form showed affinities >99%, even at bicarbonate concentrations of >3 mol·L-1. Desorption from loaded resin was carried out by a 2 mol·L-1 HCl/acetone mixture, followed by product crystallization during acetone evaporation. This presented concept does not require a final column preparation step and improves the overall atom efficiency of the biocatalytic reaction system.
- Meyer, Lars-Erik,Plasch, Katharina,Kragl, Udo,Von Langermann, Jan
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- Design, Synthesis, and Herbicidal Activity of Pyrimidine-Biphenyl Hybrids as Novel Acetohydroxyacid Synthase Inhibitors
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The issue of weed resistance to acetohydroxyacid synthase (EC 2.2.1.6, AHAS) inhibitors has become one of the largest obstacles for the application of this class of herbicides. In a continuing effort to discover novel AHAS inhibitors to overcome weed resistance, a series of pyrimidine-biphenyl hybrids (4aa-bb and 5aa-ah) were designed and synthesized via a scaffold hopping strategy. Among these derivatives, compounds 4aa (Ki = 0.09 μM) and 4bb (Ki = 0.02 μM) displayed higher inhibitory activities against Arabidopsis thaliana AHAS than those of the controls bispyribac (Ki = 0.54 μM) and flumetsulam (Ki = 0.38 μM). Remarkably, compounds 4aa, 4bb, 5ah, and 5ag exhibited excellent postemergence herbicidal activity and a broad spectrum of weed control at application rates of 37.5-150 g of active ingredient (ai)/ha. Furthermore, 4aa and 4bb showed higher herbicidal activity against AHAS inhibitor-resistant Descurainia sophia, Ammannia arenaria, and the corresponding sensitive weeds than that of bispyribac at 0.94-0.235 g ai/ha. Therefore, the pyrimidine-biphenyl motif and lead compounds 4aa and 4bb have great potential for the discovery of novel AHAS inhibitors to combat AHAS-inhibiting herbicide-resistant weeds.
- Li, Ke-Jian,Qu, Ren-Yu,Liu, Yu-Chao,Yang, Jing-Fang,Devendar, Ponnam,Chen, Qiong,Niu, Cong-Wei,Xi, Zhen,Yang, Guang-Fu
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p. 3773 - 3782
(2018/04/23)
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- Hydroxyl-Directed Cross-Coupling: A Scalable Synthesis of Debromohamigeran e and Other Targets of Interest
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A hydroxyl functional group positioned β to a pinacol boronate can serve to direct palladium-catalyzed cross-coupling reactions. This feature can be used to control the reaction site in multiply borylated substrates and can activate boronates for reaction that would otherwise be unreactive.
- Blaisdell, Thomas P.,Morken, James P.
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supporting information
p. 8712 - 8715
(2015/07/27)
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- An efficient method for syntheses of functionalized 6-bulkysubstituted salicylates under microwave irradiation
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As an important fragment and synthetic intermediate, functionalized 6-arylsalicylate substructure widely exist in pharmacologically relevant natural products and bioactive compounds. In our recent works, we discovered two highly potent inhibitors for combating mutants of acetohydroxyacid synthase (AHAS), an important target for herbicide discovery. These two inhibitors contain 6-arylsalicylate skeleton. Previously, we have explored a new method to synthesize position-6 aryl substituted salicylic acid fragment. However, this method failed to synthesize 4-methyl-6-aryl salicylic acids. Herein, we developed a new efficient method for the synthesis of functionalized 4-methyl-6-bulkyarylsalicylates via a microwave-promoted Suzuki cross-coupling. This method has obvious advantages, such as a wide range of substrates, smooth and rapid reaction, moderate to excellent yields. Due to its superiority to the traditional available methods, this protocol could be utilized to synthesize pyrimidinyl(thio)salicylic acid and its derivatives.
- Qu, Ren-Yu,Liu, Yu-Chao,Wu, Qiong-You,Chen, Qiong,Yang, Guang-Fu
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p. 8123 - 8130
(2015/12/30)
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- Regioselective ortho-carboxylation of phenols catalyzed by benzoic acid decarboxylases: A biocatalytic equivalent to the Kolbe-Schmitt reaction
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The enzyme catalyzed carboxylation of electron-rich phenol derivatives employing recombinant benzoic acid decarboxylases at the expense of bicarbonate as CO2 source is reported. In contrast to the classic Kolbe-Schmitt reaction, the biocatalytic equivalent proceeded in a highly regioselective fashion exclusively at the ortho-position of the phenolic directing group in up to 80% conversion. Several enzymes were identified, which displayed a remarkably broad substrate scope encompassing alkyl, alkoxy, halo and amino- functionalities. Based on the crystal structure and molecular docking simulations, a mechanistic proposal for 2,6-dihydroxybenzoic acid decarboxylase is presented.
- Wuensch, Christiane,Gross, Johannes,Steinkellner, Georg,Lyskowski, Andrzej,Gruber, Karl,Glueck, Silvia M.,Faber, Kurt
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p. 9673 - 9679
(2014/03/21)
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- PROCESS FOR STRAIGHTENING KERATIN FIBRES WITH A HEATING MEANS AND DENATURING AGENTS
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The invention relates to a process for straightening keratin fibres, comprising: (i) a step in which a straightening composition containing at least two denaturing agents is applied to the keratin fibres, (ii) a step in which the temperature of the keratin fibres is raised, using a heating means, to a temperature of between 110 and 250° C.
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- INHIBITORS OF STEAROYL-COA DESATURASE
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Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as, for example, obesity.
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- Reactions of fused and unfused α-pyrones with magnesium alkoxide, sodium alkoxide and water as the nucleophile: effects of chelation
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The reactions between a series of α-pyrones (two mono- and three fused) and the non-chelating base sodium alkoxide, the chelating base magnesium alkoxide and water as the nucleophile, have been studied.Aromatic and other products formed reflect the points of attack on the pyrone systems and when sodium methoxide is used the ensuing cyclisation is preferentially by aldol mechanisms.The employment of excess magnesium methoxide or ethoxide gives magnesium-chelated precursors and the nature of products now depends on these intermediates, and the protection afforded by such magnesium chelation to the reaction products.In the case of structures containing chelated β-keto ester features the chelates are screened from attack as aldol acceptors, but are effective Claisen acceptors.In such chelates an adjacent methylene is activated by further magnesium alkoxide to act as an aldol or Claisen donor.These contrasting aldol/Claisen reactivities, as between a non-chelating and a chelating base, are illustrated in the ensuing chemistry of the pyrones.Treatment with water releases the main carbon chain with decarboxylation, from which new products may form.
- Crombie, Leslie,Games, David E.,James, Alun W. G.
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p. 2715 - 2724
(2007/10/03)
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