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A facile and convenient synthesis of 3-alkylamino-5-arylthiophenes with a variety of substituents at C-2 and studies of reaction mechanisms

Thioaroylketene S,N-acetals were treated with active methylene compounds including beta-keto ester, nitromethane, cyanoacetic acid, p- toluenesulfonylacetone, 4-nitrophenylacetic acid, and diethyl (2- oxopropyl)phosphonate in the presence of mercury(II) acetate in CH2Cl2 at room temperature. These reactions gave 3-alkylamino-5-arylthiophenes containing various substituents, which comprised, respectively, alkoxycarbonyl, nitro, cyano, p-toluenesulfonyl, 4-nitrophenyl, and diethylphosphono groups at C-2 in good yields. The reaction of 3-methylamino- 3-methylthio-1-phenylthioxopropene with malonic acid or Meldrum’s acid under the same conditions gave 3-methylamino-5-phenylthiophene. Similarly, treatment of 3-methylamino-3-methylthio-1-phenylthioxopropene with various enolizable cyclic ketones such as 4-hydroxy-6-methyl-2-pyrone, homophthalic anhydride, 2-hydroxy1,4-benzoquinone, and 1,3-diethyl-2-thiobarbituric acid gave thieno[3,2-b]pyridin-4-one, thieno[3,2c]isoquinolin-5-one, thieno[3,2- c]benzazepine-1,6-dione, and thieno[3,2-d]pyrimidine-2,4-dione, respectively.

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Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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Profiling the reactivity of cyclic C-nucleophiles towards electrophilic sulfur in cysteine sulfenic acid

Oxidation of a protein cysteine thiol to sulfenic acid, termed S-sulfenylation, is a reversible post-translational modification that plays a crucial role in regulating protein function and is correlated with disease states. The majority of reaction-based small molecule and immunochemical probes used for detecting sulfenic acids are based on the 5,5-dimethyl-1,3-cyclohexanedione (dimedone) scaffold, which is selective, but suffers from low reactivity. In addition, mechanistic details and features that diminish or enhance nucleophile reactivity remain largely unknown. A significant hurdle to resolving the aforementioned issues has been the chemically unstable nature of small-molecule sulfenic acid models. Herein, we report a facile mass spectrometry-based assay and repurposed dipeptide-based model to screen a library of cyclic C-nucleophiles for reactivity with sulfenic acid under aqueous conditions. Observed rate constants for ?100 cyclic C-nucleophiles were obtained and, from this collection, we have identified novel compounds with more than 200-fold enhanced reactivity, as compared to dimedone. The increase in reactivity and retention of selectivity of these C-nucleophiles were validated in secondary assays, including a protein model for sulfenic acid. Together, this work represents a significant step toward developing new chemical reporters for detecting protein S-sulfenylation with superior kinetic resolution. The enhanced rates and varied composition of the C-nucleophiles should enable more comprehensive analyses of the sulfenome and serve as the foundation for reversible or irreversible nucleophilic covalent inhibitors that target oxidized cysteine residues in therapeutically important proteins.

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Reference:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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Cutting-Edge and Time-Honored Strategies for Stereoselective Construction of C-N Bonds in Total Synthesis

The main objective of this review is to provide a comprehensive survey of methods used for stereoselective construction of carbon-nitrogen bonds during the total synthesis of nitrogen-containing natural products that have appeared in the literature since 2000. The material is organized by specific reaction in order of decreasing number of applications in natural product synthesis. About 800 total syntheses of natural products with stereogenic carbon-nitrogen bonds described since 2000 have been reviewed.

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Reference:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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A facile one pot C[sbnd]C and C[sbnd]N bond formation for the synthesis of spiro-benzodiazepines and their cytotoxicity

An efficient, multicomponent and environmentally benign protocol has been developed for the synthesis of spiro-benzodiazepines through C[sbnd]C and C[sbnd]N bond formations in a single step. This one-pot protocol proceeds via three component reaction of o-phenylenediamines, tetronic acid and isatins by using mild and inexpensive catalyst like sulphamic acid in water. A variety of spiro-benzodiazepine derivatives has been synthesized in excellent yields by using this protocol in a shorter reaction time. All the synthesized compounds were evaluated for their cytotoxic potential on different human cancer cell lines and most of the compounds exhibited moderate to good cytotoxic activity, while some of them like 4f, 4h, 4i, 4j and 4q showed promising cytotoxicity with IC50 values ranging between 1.14 and 1.69 muM.

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Reference:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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Lactic acid was used, for the first time, as a bio-based green solvent to promote some organic reactions, such as three-component reactions of styrenes, formaldehyde and an active phenolic compound or N,N-dialkylacetoacetamides, three-component reactions of diethyl acetylenedicarboxylate, anilines and aromatic aldehydes, aniline-catalyzed condensations between salicylaldehydes and diethyl acetylenedicarboxylate, and the synthesis of substituted quinolines through Friedlaender annulation between 2?-aminoacetophenone and 1,3-dicarbonyl compounds. In these reactions, lactic acid solvent exhibited many advantages including bio-based origin, superior synthetic efficiency, ease of isolating the product and good recyclability of the reaction medium. The concept of using lactic acid as a green solvent not only enriches the diversity and versatility of bio-based green solvents, but also offers us an effective means for designing environmentally benign synthetic systems.

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Reference:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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We aim to provide an overview of the objectives achieved by metabolomics in relation to plant-food intake, paying attention to the new biomarkers, the influence of the gut microbiota and the modifications of the human metabolome resulting. The information included will help the design and the production of further manufactured foods with interesting health effects, hence enhancing our capacity to modulate metabolic pathways through the diet.

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Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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A mild, efficient, and environmentally benign one-pot synthesis of functionalized chromeno[4,3-b]pyrrol-4(1H)-ones by a three-component domino reaction of 4-aminocoumarins, arylglyoxal monohydrates, and 1,3-dicarbonyl compounds in refluxing ethanol without the use of catalyst is reported. The present protocol features operational simplicity, short reaction time, good yields, and the absence of aqueous workup procedure and chromatographic separation.

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Reference:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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Iminium Carbonic Acid Derivative Salts. VIII [1]. Electrophilic Reactions of 2-Methylthio-5,6-dihydro-1,3-thiazinium Iodides, 2-Methylthio-5,6-dihydrothiazolium Iodides and 5-Methyl-2-methylthiothiazolium Iodides. Part II. with Active Methylene Compounds

The title compounds 1a-c and 2 were reacted with several doubly activated methylene components to yield the cyclic ketene S,N-acetals 3-10.

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Reference:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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Br°nsted acid-promoted synthesis of common heterocycles and related bio-active and functional molecules

Various heterocyclic systems based on natural and unnatural biologically active products were synthesized by Br°nsted acid-promoted cyclization. We have made an attempt to summarize the progress made in this area during the period 2005 to 2015. This article describes the synthetic routes of these heterocycles that involve a Br°nsted acid-promoted cyclization as a crucial step or Br°nsted acids as co-catalysts with other transition metals.

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Reference:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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Tautomerism in 3-nitrotetronic acids

The controversial structure of the title compounds has been established.The previously reported strong intramolecular hydrogen bond was found to be absent.

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Reference:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem