- Catalytic hydrogenation of α,β-unsaturated carboxylic acid derivatives using copper(i)/N-heterocyclic carbene complexes
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A simple and air-stable copper(i)/N-heterocyclic carbene complex enables the catalytic hydrogenation of enoates and enamides, hitherto unreactive substrates employing homogeneous copper catalysis and H2 as a terminal reducing agent. This atom economic transformation replaces commonly employed hydrosilanes and can also be carried out in an asymmetric fashion.
- Zimmermann, Birte M.,Kobosil, Sarah C. K.,Teichert, Johannes F.
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p. 2293 - 2296
(2019/02/27)
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- Optimization of a Novel Quinazolinone-Based Series of Transient Receptor Potential A1 (TRPA1) Antagonists Demonstrating Potent in Vivo Activity
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There has been significant interest in developing a transient receptor potential A1 (TRPA1) antagonist for the treatment of pain due to a wealth of data implicating its role in pain pathways. Despite this, identification of a potent small molecule tool possessing pharmacokinetic properties allowing for robust in vivo target coverage has been challenging. Here we describe the optimization of a potent, selective series of quinazolinone-based TRPA1 antagonists. High-throughput screening identified 4, which possessed promising potency and selectivity. A strategy focused on optimizing potency while increasing polarity in order to improve intrinisic clearance culminated with the discovery of purinone 27 (AM-0902), which is a potent, selective antagonist of TRPA1 with pharmacokinetic properties allowing for >30-fold coverage of the rat TRPA1 IC50 in vivo. Compound 27 demonstrated dose-dependent inhibition of AITC-induced flinching in rats, validating its utility as a tool for interrogating the role of TRPA1 in in vivo pain models.
- Schenkel, Laurie B.,Olivieri, Philip R.,Boezio, Alessandro A.,Deak, Holly L.,Emkey, Renee,Graceffa, Russell F.,Gunaydin, Hakan,Guzman-Perez, Angel,Lee, Josie H.,Teffera, Yohannes,Wang, Weiya,Youngblood, Beth D.,Yu, Violeta L.,Zhang, Maosheng,Gavva, Narender R.,Lehto, Sonya G.,Geuns-Meyer, Stephanie
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p. 2794 - 2809
(2016/04/10)
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- Reduction of benzylic alcohols and α-hydroxycarbonyl compounds by hydriodic acid in a biphasic reaction medium
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The synthetic protocol for the reduction of alcohols to hydrocarbons by using hydriodic acid, first described by Kiliani more than 140 years ago, was improved to be more applicable to organic synthesis. Instead of a strongly acidic, aqueous solution, a biphasic toluene-water reaction medium was used, which allowed the conversion of primary, secondary and tertiary benzylic alcohols, in good yields and short reaction times, into the corresponding hydrocarbons. Red phosphorous was used as the stoichiometric reducing agent. Keto, ester, amide or ether groups are tolerated, and catalytic amounts of hydriodic acid (0.2 equiv) in the presence of 0.6 equiv phosphorous are sufficient to achieve conversion.
- Dobmeier, Michael,Herrmann, Josef M.,Lenoir, Dieter,Koenig, Burkhard
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supporting information; experimental part
p. 330 - 336
(2012/05/20)
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- New application possibilities of Reformatzky reagent for synthesis of substituted acetic acid ethyl ester
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When generated in dichloromethane, the Reformatzky reagent from ethyl bromoacetate can react with diphenylchloromethane, 1-bromoadamantane and 1-phenylethyl chlorides to form the corresponding α-substituted ethyl acetates in excellent to good yields. The mechanism of these Reformatzky reactions is interpreted in terms of a carbocation as intermediate which originates from the interaction of the alkyl halide with the organozinc bromide.
- Bott
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p. 555 - 556
(2007/10/02)
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- Synthesis of 3-Phenoxybenzyl 3-Alkyl-3-phenyl-/p-substituted phenyl and 3-Phenoxybenzyl 2-Alkyl-3-phenyl-/p-substituted phenylpropionates
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Some 3-phenoxybenzyl 3-alkyl-3-phenyl-/p-substituted phenylpropionates (VII, XI, XV, XIX, XXIII, XXVII) which resemble structurally the 1,2-secopyrethroids, have been prepared employing simple reactions like alkylation, decarbethoxylation and transesterification.The synthesis of 3-phenoxybenzyl 2-alkyl-3-phenyl-/p-substituted phenyl-propionates (XXXI, XXXII, XXXIII, and XXXVI) bearing close structural resemblance to 2,3-secopyrethroids has also been described.
- Kelkar, S. V.,Joshi, G. S.,Kulkarni, G. H.,Mitra, R. B.
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