- Expedient Pd-Catalyzed α-Arylation towards Dibenzoxepinones: Pivotal Manske's Ketone for the Formal Synthesis of Cularine Alkaloids
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The general synthesis of diversely substituted dibenzoxepinones by a combined Pd-catalyzed α-arylation and SNAr strategy is reported and applied to the synthesis of Manske's ketone, a key intermediate en route to the total synthesis of cularine alkaloids. In the course of this work, an unanticipated ring contraction reaction to a xanthone was observed and serves as a caveat for the conditions of the widely used α-arylation reaction.
- Deichert, Julie A.,Mizufune, Hideya,Patel, Jignesh J.,Hurst, Timothy E.,Maheta, Ashish,Kitching, Matthew O.,Ross, Avena C.,Snieckus, Victor
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p. 4693 - 4697
(2020/05/08)
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- Optimization of thiazole analogues of resveratrol for induction of NAD(P)H:quinone reductase 1 (QR1)
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NAD(P)H:quinone reductase 1 (QR1) belongs to a class of enzymes called cytoprotective enzymes. It exhibits its cancer protective activity mainly by inhibiting the formation of intracellular semiquinone radicals, and by generating α-tocopherolhydroquinone, which acts as a free radical scavenger. It is therefore believed that QR1 inducers can act as cancer chemopreventive agents. Resveratrol (1) is a naturally occurring stilbene derivative that requires a concentration of 21 μM to double QR1 activity (CD = 21 μM). The stilbene double bond of resveratrol was replaced with a thiadiazole ring and the phenols were eliminated to provide a more potent and selective derivative 2 (CD = 2.1 μM). Optimizing the substitution pattern of the two phenyl rings and the central heterocyclic linker led to a highly potent and selective QR1 inducer 9o with a CD value of 0.087 μM.
- Mayhoub, Abdelrahman S.,Marler, Laura,Kondratyuk, Tamara P.,Park, Eun-Jung,Pezzuto, John M.,Cushman, Mark
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p. 7030 - 7039
(2013/01/15)
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- Antibacterial alkoxybenzamide inhibitors of the essential bacterial cell division protein FtsZ
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3-Methoxybenzamide is a weak inhibitor of the essential bacterial cell division protein FtsZ. Exploration of the structure-activity relationships of 3-methoxybenzamide analogues led to the identification of potent anti-staphylococcal compounds.
- Czaplewski, Lloyd G.,Collins, Ian,Boyd, E. Andrew,Brown, David,East, Stephen P.,Gardiner, Mihaly,Fletcher, Rowena,Haydon, David J.,Henstock, Vincent,Ingram, Peter,Jones, Clare,Noula, Caterina,Kennison, Leanne,Rockley, Chris,Rose, Valerie,Thomaides-Brears, Helena B.,Ure, Rebecca,Whittaker, Mark,Stokes, Neil R.
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scheme or table
p. 524 - 527
(2011/02/28)
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- Synthesis of [1]Benzothieno[3,2-d]pyrimidines Substituted with Electron Donating Substituents on the Benzene Ring
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Various 2-fluorobenzonitriles were converted to the corresponding 3-amino[1]benzothiophenecarboxylic acid esters, which in turn were annulated with formamidine or various equivalents to produce the desired tricyclic benzothienopyrimidines. Various methoxy and nitro/amino substituants were placed on the phenyl ring, requiring several different strategies to prepare the desired benzothiophenes. Several different pyrimidone annulations were also required. The use of an electron rich 2-bromobenzonitrile in a four-step one-pot low temperature lithiation sequence to produce highly electron-rich amino[1]benzothiophenecarboxylate esters is also described. The synthesis of 7-amino-8-fluoro[1]benzothieno[3,2-d]pyrimid-4(3H)-one was relatively straightforward, but synthesis of the corresponding 7-amino-8-protio analogue proved to be very difficult, and required several approaches before a successful one was found.
- Bridges, Alexander J.,Zhou, Hairong
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p. 1163 - 1172
(2007/10/03)
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