Bypassing Biocatalytic Substrate Limitations in Oxidative Dearomatization Reactions by Transient Substrate Mimicking
Enzymatic oxidative dearomatization is an efficient way to generate chiral molecules from simple arenes. One example is the flavin-dependent monooxygenase SorbC involved in sorbicillinoid biosynthesis. However, SorbC requires a long-chain keto substituent at its phenolic substrate, thus preventing its application beyond the synthesis of natural sorbicillinoids or close structural analogues. This work describes an approach to broaden the accessible product spectrum of SorbC by employing an ester functionality mimicking the natural substrate structure during enzymatic oxidation.
Milzarek, Tobias M.,Einsiedler, Manuel,Aldemir, Hülya,D'Agostino, Paul M.,Evers, Julia K.,Hertrampf, Gesa,Lamm, Katharina,Malay, Mert,Matura, Anke,Müller, Jonas I.,Gulder, Tobias A. M.
supporting information
p. 4520 - 4524
(2019/06/27)
Catalytic depolymerization of alkali lignin in subcritical water: Influence of formic acid and Pd/C catalyst on the yields of liquid monomeric aromatic products
Alkali lignin was subjected to depolymerization in subcritical water at 265 °C, 6.5 MPa for reaction times between 1-6 h in a batch reactor and in the presence of formic acid (FA) and Pd/C catalyst. The oil products were extracted into diethyl ether and contained >90% of single-ring phenolic compounds. The reaction of lignin in subcritical water alone yielded 22.3 wt% oil containing 56% guaiacol as the main product. A maximum oil yield of 33.1 wt% was obtained when the lignin was reacted in the presence of formic acid alone. In the presence of FA, catechol became the predominant compound, with more than 80% of the ether extract after 6 h. The conversion of guaiacol to catechol in the presence of formic acid suggested the hydrolysis of O-CH3 ether bonds. In addition, the yields of alkyl guaiacols increased in the presence of FA. The use of 5 wt% Pd/C catalyst with FA slightly decreased the yields of oil products but led to compounds indicative of hydrogenolysis of aryl-O ether bonds as well as hydrogenation of CC bonds.
Onwudili, Jude A.,Williams, Paul T.
p. 4740 - 4748
(2014/12/11)
Design and synthesis of systemically active metabotropic glutamate subtype-2 and -3 (mGlu2/3) receptor positive allosteric modulators (PAMs): Pharmacological characterization and assessment in a rat model of cocaine dependence
As part of our ongoing small-molecule metabotropic glutamate (mGlu) receptor positive allosteric modulator (PAM) research, we performed structure-activity relationship (SAR) studies around a series of group II mGlu PAMs. Initial analogues exhibited weak activity as mGlu2 receptor PAMs and no activity at mGlu3. Compound optimization led to the identification of potent mGlu2/3 selective PAMs with no in vitro activity at mGlu1,4-8 or 45 other CNS receptors. In vitro pharmacological characterization of representative compound 44 indicated agonist-PAM activity toward mGlu2 and PAM activity at mGlu 3. The most potent mGlu2/3 PAMs were characterized in assays predictive of ADME/T and pharmacokinetic (PK) properties, allowing the discovery of systemically active mGlu2/3 PAMs. On the basis of its overall profile, compound 74 was selected for behavioral studies and was shown to dose-dependently decrease cocaine self-administration in rats after intraperitoneal administration. These mGlu2/3 receptor PAMs have significant potential as small molecule tools for investigating group II mGlu pharmacology.
Dhanya, Raveendra-Panickar,Sheffler, Douglas J.,Dahl, Russell,Davis, Melinda,Lee, Pooi San,Yang, Li,Nickols, Hilary Highfield,Cho, Hyekyung P.,Smith, Layton H.,D'Souza, Manoranjan S.,Conn, P. Jeffrey,Der-Avakian, Andre,Markou, Athina,Cosford, Nicholas D.P.
p. 4154 - 4172
(2014/06/09)
Phenyl-tetrazolyl acetophenones: Discovery of positive allosteric potentiatiors for the metabotropic glutamate 2 receptor
Herein we disclose the discovery of a new class of positive allosteric potentiators of the metabotropic glutamate receptor 2 (mGlu2), phenyl-tetrazolyl acetophenones, e.g. 1-(2-hydroxy-3-propyl-4-{4-[4-(2H-tetrazol-5-yl)phenoxy] butoxy}phenyl) ethanone (4
Pinkerton, Anthony B.,Vernier, Jean-Michel,Schaffhauser, Hervé,Rowe, Blake A.,Campbell, Una C.,Rodriguez, Dana E.,Lorrain, Daniel S.,Baccei, Christopher S.,Daggett, Lorrie P.,Bristow, Linda J.
p. 4595 - 4599
(2007/10/03)
Allosteric potentiators of the metabotropic glutamate receptor 2 (mGlu2). Part 1: Identification and synthesis of phenyl-tetrazolyl acetophenones
We have identified and synthesized a series of aryl-tetrazoyl acetophenones as positive allosteric potentiators of the metabotropic glutamate receptor 2. Structure activity relationship studies directed toward improving the potency and level of potentiation led to the discovery of 22 (EC50 = 93 nM, 128% potentiation). We have identified and synthesized a series of aryl-tetrazoyl acetophenones as positive allosteric potentiators of the metabotropic glutamate receptor 2. Structure activity relationship studies directed toward improving the potency and level of potentiation led to the discovery of 22 (EC50 = 93 nM, 128% potentiation).
Pinkerton, Anthony B.,Cube, Rowena V.,Hutchinson, John H.,Rowe, Blake A.,Schaffhauser, Hervé,Zhao, Xiumin,Daggett, Lorrie P.,Vernier, Jean-Michel
p. 5329 - 5332
(2007/10/03)
The Synthesis of Indan-1-ones and Isocoumarins
A flexible synthetic route leading via indan-1-ones to variously methylated and oxygenated isocoumarins is described.The indanones are prepared by alternative routes involving intramolecular Friedel-Crafts cyclisation of arylpropionic acids or pericyclic ring closure of acrylophenones.The influence of substitution on the rate of the pericyclic reaction is assessed.
Carter, Rachel H.,Garson, Mary J.,Hill, Robert A.,Staunton, James,Sunter, David C.
p. 471 - 479
(2007/10/02)
More Articles about upstream products of 63876-46-0