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Modular Access to Chiral 2,3-Dihydrofurans and 3,4-Dihydro-2 H-pyrans by Stereospecific Activation of Formylcyclopropanes through Combination of Organocatalytic Reductive Coupling and Lewis-Acid-Catalyzed Annulative Ring-Opening Reactions

An organocatalytic reductive coupling and Lewis-acid-catalyzed annulative ring-opening strategy is developed as a two-step protocol for the stereoselective synthesis of dihydropyrans as the major products from the chiral formylcyclopropanes, CH acids, and Hantzsch ester. It is an efficient, catalytic, two-step protocol for the chiral synthesis of dihydropyrans and dihydrofurans. Structurally important and challenging functionally rich cyclopropanes containing cyclic-1,3-diones were synthesized in very good yields with excellent chemo-, enantio-, and diastereoselectivities from the readily available starting materials, chiral formylcyclopropanes, cyclic-1,3-diones, or CH acids and Hantzsch ester through an organocatalytic reductive coupling reaction at ambient conditions, especially without harming the cyclopropane ring. Chiral cyclopropanes containing cyclic-1,3-diones were stereospecifically transformed into dihydropyrans and dihydrofurans found in many bioactive natural products and drugs through an annulative ring-opening reaction by using Lewis-acid (BF3¡¤OEt2) or cesium carbonate (Cs2CO3) catalysis. Highly diastereo- and regioselective ring opening of cyclopropanes was explained through a stereospecific intimate ion pair pathway.

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

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Bioorganopromoted green Friedlaender synthesis: a versatile new malic acid promoted solvent free approach to multisubstituted quinolines

The discovery of a new, malic acid promoted, eco-friendly Friedlaender approach to varied multisubstituted quinolines is disclosed. To the best of our knowledge, this is the first report on the use of malic acid, classified as one of the 12 biobased hot molecules by the US Department of Energy, as an organopromoter in organic synthesis and includes many benefits like wide substrate scope, solvent free ambient reaction conditions, short reaction times, operational simplicity, cost effectiveness, high atom economy, good to excellent yields, and recylability of the organopromoter, making it a valuable green alternative to the existing methods. The versatility and practicability of the developed method was further established by its successful application towards the targeted synthesis of some important quinoline molecules and successful scale up.

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

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ANALOGS OF CYP-EICOSANOIDS FOR USE IN TREATING OR PREVENTING A DISORDER ASSOCIATED WITH NEOVASCULARIZATION AND/OR INFLAMMATION

The present invention relates to compounds according to general formula (I) which are metabolically robust analogues of bioactive lipid mediators derived from omega-3 polyunsaturated fatty acids (n-3 PUFAs) for use in treating or reducing the risk of developing or preventing: (i) neovascularization and/or (ii) inflammatory disorder, in particular, ophthalmic disorders associated with neovascularization and/or inflammation.

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

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Transition metal-free controlled synthesis of bis[(trifluoromethyl)sulfonyl]ethyl-decorated heterocycles

Several heterocycles reacted with shelf-stable 2-(2-fluoropyridinium-1-yl)-1,1-bis[(trifluoromethyl)sulfonyl] ethan-1-ide, a latent Tf2CCH2 source, to give rise in a mild and controllable way to adducts via direct C-H bis[(trifluoromethyl)sulfonyl]ethylation reactions. This metal- and irradiation-free protocol is convenient. Besides, the volatile side-product 2-fluoropyridine can be smoothly eliminated under vacuum, which facilitates purification. The substrate scope survey discloses that exquisite chemo- and regioselectivities are achieved in a variety of heterocyclic systems. Of particular interest are the late-stage structural modification of known pharmaceuticals, such as the marketed drugs Phenazone (Antipyrine) and Edaravone, and the development of a water soluble fluorescent dye.

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

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BICYCLIC ENAMINO(THIO)CARBONYL COMPOUNDS

The present invention relates to novel bicyclic enamino(thio)carbonyl compounds, to processes for their preparation and to their use for controlling animal pests, especially arthropods, in particular insects.

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Biased multicomponent reactions to develop novel bromodomain inhibitors

BET bromodomain inhibition has contributed new insights into gene regulation and emerged as a promising therapeutic strategy in cancer. Structural analogy of early methyl-triazolo BET inhibitors has prompted a need for structurally dissimilar ligands as probes of bromodomain function. Using fluorous-tagged multicomponent reactions, we developed a focused chemical library of bromodomain inhibitors around a 3,5-dimethylisoxazole biasing element with micromolar biochemical IC50. Iterative synthesis and biochemical assessment allowed optimization of novel BET bromodomain inhibitors based on an imidazo[1,2-a]pyrazine scaffold. Lead compound 32 (UMB-32) binds BRD4 with a Kd of 550 nM and 724 nM cellular potency in BRD4-dependent lines. Additionally, compound 32 shows potency against TAF1, a bromodomain-containing transcription factor previously unapproached by discovery chemistry. Compound 32 was cocrystallized with BRD4, yielding a 1.56 A resolution crystal structure. This research showcases new applications of fluorous and multicomponent chemical synthesis for the development of novel epigenetic inhibitors.

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Polyalkoxybenzenes from plants. 5. parsley seed extract in synthesis of azapodophyllotoxins featuring strong tubulin destabilizing activity in the sea urchin embryo and cell culture assays

A series of 4-azapodophyllotoxin derivatives with modified rings B and E have been synthesized using allylpolyalkoxybenzenes from parsley seed oil. The targeted molecules were evaluated in vivo in a phenotypic sea urchin embryo assay for antimitotic and tubulin destabilizing activity. The most active compounds identified by the in vivo sea urchin embryo assay featured myristicin-derived ring E (4e, 6e, and 8e). These molecules were determined to be more potent than podophyllotoxin. Cytotoxic effects of selected molecules were further confirmed and evaluated by conventional assays with A549 and Jurkat human leukemic T-cell lines including cell growth inhibition, cell cycle arrest, cellular microtubule disruption, and induction of apoptosis. The ring B modification yielded 6-OMe substituted molecule 8e as the most active compound. Finally, in Jurkat cells, compound 8e induced caspase-dependent apoptosis mediated by the apical caspases-2 and -9 and not caspase-8, implying the involvement of the intrinsic caspase-9-dependent apoptotic pathway.

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Tetrahydrofuran – Wikipedia,
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FURANONE COMPOUNDS AND LACTAM ANALOGUES THEREOF

The present invention provides a compound of formula I and a compound of formula II, methods of use and formulations thereof.

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Tetrahydrofuran – Wikipedia,
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Recent application of isocyanides in synthesis of heterocycles

The recent isocyanide-based synthesis of various types of heterocycles is reviewed. The report contains 98 references. 2011 Elsevier Ltd

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Tetrahydrofuran – Wikipedia,
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Synthesis of a terphenyl substituted 4-aza-2,3-didehydropodophyllotoxin analogues as inhibitors of tubulin polymerization and apoptosis inducers

A series of terphenyl based 4-aza-2,3-didehydropodophyllotoxin conjugates (8a-r) were synthesized by a straightforward one-step multicomponent synthesis that demonstrated anticancer activity against five human cancer cell lines (lung, colon, renal, prostate and cervical). All the tested compounds showed potent anticancer activity with IC50 values ranging from 0.87 to 16.59 muM. Among them compounds 8n and 8p showed significant anticancer activity in lung cancer cells with IC50 values 0.91 and 0.87 muM, respectively. Flow cytometric analysis revealed that these compounds induced cell cycle arrest in G2/M phase in A549 cell line leading to caspase-3 dependent apoptotic cell death. The tubulin polymerization assay and immunofluorescence analysis showed that these compounds effectively inhibit microtubule assembly at both molecular and cellular levels in A549 cells. Further, Hoechst staining, DNA fragmentation analysis also suggested that these compounds induced cell death by apoptosis. Overall, the current study demonstrated that the synthesis of terphenyl based 4-aza-2,3- didehydropodophyllotoxin conjugates as promising anticancer agents with G 2/M cell cycle arrest and apoptotic-inducing activities via targeting tubulin.

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Tetrahydrofuran – Wikipedia,
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