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Herein, we describe a Cu-catalyzed approach to directly accessing aromatic heterocyclic amines from cyclic amides. The most-reported methods for cyclic amide conversions to aromatic heterocyclic amines use an activating group, such as a halogen atom or a trifluoromethane sulfonyl group. However, subsequent elimination of activating groups during the amination process results in significant waste. This copper-catalyzed direct amination of cyclic amides in DMF forms aromatic heterocyclic amines with environmental friendliness and readily available reagents. A plausible radical mechanism has been proposed for the reaction. Meanwhile, the coordinating effect of the N1 atom is key to the success of this reaction, which provides assistance to the copper ions for the activation and amination of C–O bonds.
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Herein, we report an elemental sulfur-promoted switchable redox condensation reaction that can selectively prepare 2-aminofurans and 2-aminothiophenes from the corresponding enaminones and methylene nitriles, respectively. Mechanistic studies demonstrated that the enaminones, as dual nucleophiles, reacted with nitrile acetate to produce 2-aminofurans via 3,5-annulation under promotion by elemental sulfur. These reactions used readily available starting materials, transition metal-free, eco-friendly procedures, gram-scale syntheses, and wide functional group tolerance. The methodology may be useful for the construction of 2-aminofuran and 2-aminothiophene derivatives with potential biological activity.
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Herein, we report a green cascade approach to prepare a variety of diastereoselective polysubstituted cyclopentene derivatives through metal-free oxidative [2 + 1 + 1 + 1] annulation of aldehydes and methylene nitriles. Mechanistic studies demonstrated that the reaction underwent a four-step cascade reaction including air oxidation and Michael addition to obtain the final product. This reaction features readily available starting materials, transition metal-free, eco-friendly operations, gram-scale syntheses, and wide functional group tolerance. The methodology may be useful for the construction of polysubstituted cyano-cyclopentene heterocycles with potential biological activity.
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Herein, we have carried out a structural optimization campaign to discover the novel anti-tumor agents with our previously screened YQY-26 as the hit compound. A library of thirty-seven 6-amide-2-aryl benzoxazole/benzimidazole derivatives has been designed and synthesized based on the highly conserved active site of VEGFR-2. Several title compounds exhibited selective inhibitory activities against VEGFR-2 than EGFR kinases, which also displayed selective anti-proliferation potency against the HUVEC and HepG2 than the A549 and MDA-MB-231 cancer cell lines. The newly synthesized compounds were evaluated for anti-angiogenesis capability by chick chorioallantoic membrane (CAM) assay. Among them, compounds 9d showed the most potent anti-angiogenesis ability (79% inhibition at 10 nM/eggs), the efficient cytotoxic activities (in vitro against the HUVEC and HepG2 cell lines with IC50 values of 1.47 and 2.57 μM, respectively), and excellent VEGFR-2 kinase inhibition (IC50 = 0.051 μM). The molecular docking analysis revealed that compound 9d is a Type II inhibitor of VEGFR-2 kinase. These results indicated that the 6-amide-2-arylbenzoxazole and 6-amide-2-aryl benzimidazole derivatives are promising inhibitors of VEGFR-2 kinase for the potential treatment of anti-angiogenesis.
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本发明公开了一种多取代氢化苯并环醚衍生物及其制备方法，属于有机化学技术领域，包括Ⅰ类多取代氢化苯并环醚衍生物或Ⅱ类多取代氢苯并环醚衍生物；

A metal-free dual C(sp3)−H bond functionalization of saturated cyclic ethers via photooxidative singlet oxygenmediated ring opening and ring closing has been developed, providing a method for generating hydrobenzofurans/pyrans/dioxins. Mechanistic studies have confirmed that ring-opening intermediates were effectively generated by singlet oxygenmediated C(sp3)−H activation and efficiently reacted with aldehydes and activated methylene compounds to form a wide array of products with high diastereoselectivities (up to >95:5 dr).This study is a rare example of α,β-dual C(sp3)−H bond functionalization of ethers.
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Lawsones and indenopyrazoles are the prevalent structural motifs and building blocks in pharmaceuticals and bioactive molecules, but their synthesis has always remained challenging as no comprehensive protocol has been outlined to date. Herein, a metal-free, ring-expansion reaction of indantrione with diazomethanes, generated in situ from the N-tosylhydrazones, has been developed for the synthesis of lawsone and indenopyrazole derivatives in acetonitrile and alcohol solvents, respectively. It provides these valuable lawsone and pyrazole skeletons in good yields and high levels of diastereoselectivity from simple and readily available starting materials. DFT calculations were used to explore the mechanism in different solutions. The synthetic application example also showed the prospects of this method for the preparation of valuable compounds.
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