- S-methylation of 2-mercaptopyrazine in rat liver microsomes and cytosol
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1. 2-(Allylthio)pyrazine (2-AP) has been demonstrated to protect the liver against toxicants by inhibiting CYP2E1 activity. Since 2-mercaptopyrazine (2-MP) is presumed to be a metabolite of 2-AP, the experiments were performed to determine whether rat liver microsomal and/or cytosolic preparations could catalyse the S-methylation of 2-MP. 2. It was found that both rat liver microsomes and cytosol could catalyse the S-methylation of 2-MP. The microsomal activity displayed biphasic substrate kinetics, with apparent K(m) = 8.44 ± 2.68 and 417 ± 74 μM for the high- and low-affinity activities respectively. The high-affinity activity had an apparent K(m) for S-adenosyl-L-methionine (Ado-Met) of 3.52 μM. The cytosolic activity also displayed biphasic substrate kinetics, with apparent K(m) of 3.26 ± 0.62 and 91.6 ± 23.1 μM for the high- and low-affinity activities respectively. 3. The microsomal S-methylation of 2-MP was inhibited by 2,3-dichloro-α-methylbenzylamine (DCMB), SKF-525A and benzylamine, known microsomal thiol methyltransferase (TMT) inhibitors, whereas cytosolic activity was inhibited by anisic acid and 3-chlorobenzoate, which also inhibit cytosolic thiopurine methyltransferase (TPMT). Both activities were inhibited by S-adenosyl-L-homocysteine (Met-Hcy). 4. These results suggest that both TMT and TPMT may be involved in the in vivo methylation of 2-MP.
- Lee,Kim
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- BF3·SMe2 for Thiomethylation, Nitro Reduction and Tandem Reduction/SMe Insertion of Nitrogen Heterocycles
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Herein, a general, solvent-free and straightforward thiomethylation of electron deficient heterocycles using BF3·SMe2 as a dual thiomethyl source and Lewis acidic activator is presented. A range of heterocycles including pyrimidine, pyrazine, pyridazine, thiazole and purine derivatives were successfully substituted using this method. An unexpected reductive property of BF3·SMe2 towards nitropyridines was also discovered including an intriguing tandem reduction/SMe insertion process in certain substrates. Notable features of the present work include its convenience and use of a non-malodorous reagent while the discovery of novel chemical transformations using BF3·SMe2 provides fundamental new insights into the reactivity of this commonly employed reagent.
- S?derstr?m, Marcus,Zamaratski, Edouard,Odell, Luke R.
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p. 5402 - 5408
(2019/06/27)
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- A visible-light photocatalytic thiolation of aryl, heteroaryl and vinyl iodides
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The general catalytic synthesis of aryl and vinyl thioethers from readily available halides remains a challenge. Herein we report a unified method for the thiolation of aryl and vinyl iodides with dialkyl disulfides using visible light photoredox catalysis. A range of thioether products bearing diverse functional groups can be accessed in high yield and with excellent chemoselectivity. We demonstrate the versatility of this method through the expedient synthesis of a family of thioether-rich natural products. A detailed investigation of the photocatalytic mechanism is presented from both steady-state and time-resolved luminescent quenching as well as transient absorption spectroscopy experiments.
- Czyz,Weragoda,Monaghan,Connell,Brzozowski,Scully,Burton,Lupton,Polyzos
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supporting information
p. 1543 - 1551
(2018/03/08)
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- Room temperature cross-coupling of highly functionalized organozinc reagents with thiomethylated N-heterocycles by nickel catalysis
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Chemical Equation Presented A variety of thiomethyl-substituted N-heterocycles such as pyridines, isoquinolines, pyrimidines, pyrazines, pyridazines, quinazolines, triazines, benzothiazoles, or benzoxazoles undergo smooth Ni-catalyzed cross-coupling reactions with functionalized aryl-, heteroaryl-, alkyl-, and benzylic zinc reagents using an inexpensive Ni(acac)2/ DPE-Phos catalytic system at 25°C.
- Melzig, Laurin,Metzger, Albrecht,Knochel, Paul
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supporting information; experimental part
p. 2131 - 2133
(2010/06/12)
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- One-Pot Two-Step Synthesis of Aryl Sulfur Compounds by Photoinduced Reactions of Thiourea Anion with Aryl Halides
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(Equation presented) The photoinduced reactions of aryl halides with the thiourea anion afford arene thiolate ions in DMSO. These species without isolation, and by a subsequent aliphatic nucleophilic substitution, S RN1 reaction, oxidation, or protonation, yield aryl methyl sulfides, diaryl sulfides, diaryl disulfides, and aryl thiols with good yields (50-80%). This is a simple and convenient approach which involves the use of the commercially available and inexpensive thiourea in a one-pot two-step process for the synthesis of aromatic sulfur compounds.
- Argueello, Juan E.,Schmidt, Luciana C.,Penenory, Alicia B.
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p. 4133 - 4136
(2007/10/03)
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- Efficient nucleophilic substitution reactions of pyrimidyl and pyrazyl halides with nucleophiles under focused microwave irradiation
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Rapid nucleophilic displacement reactions of 2-chloropyrimidine, 2-bromopyrimidine, 5-bromopyrimidine and chloropyrazine with nucleophiles under microwave irradiation was complete within several minutes with yields up to 99%. The method using microwave irradiation is superior to the classical heating processes.
- Cherng, Yie-Jia
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p. 887 - 890
(2007/10/03)
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