The Oxime Ethers with Heterocyclic,Alicyclic and Aromatic Moiety as Potential Anti-Cancer Agents

Chemotherapy is one of the most commonly used methods of cancer disease treatment. Due to the acquisition of drug resistance and the possibility of cancer recurrence, there is an urgent need to search for new molecules that would be more effective in destroying cancer cells. In this study, 1-(benzofuran-2-yl)ethan-1-one oxime and 26 oxime ethers containing heterocyclic, alicyclic or aromatic moiety were screened for their cytotoxicity against HeLa cancer cell line. The most promising derivatives with potential antitumor activity were 2-(cyclohexylideneaminoxy)acetic acid (18) and (E)-acetophenone O-2-morpholinoethyl oxime (22), which reduced the viability of HeLa cells below 20% of control at concentrations of 100–250 μg/mL. Some oxime ethers, namely thiazole and benzothiophene derivatives (24–27), also reduced HeLa cell viability at similar concentrations but with lower efficiency. Further cytotoxicity evaluation confirmed the specific toxicity of (E)-acetophenone O-2-morpholinoethyl oxime (22) against A-549, Caco-2, and HeLa cancer cells, with an EC50 around 7 μg/mL (30 μM). The most potent and specific compound was (E)-1-(benzothiophene-2-yl)ethanone O-4-methoxybenzyl oxime (27), which was selective for Caco-2 (with EC50 116 μg/mL) and HeLa (with EC50 28 μg/mL) cells. Considering the bioavailability parameters, the tested derivatives meet the criteria for good absorption and permeation. The presented results allow us to conclude that oxime ethers deserve more scientific attention and further research on their chemotherapeutic activity.     

Direct Dimesitylborylation of Benzofuran Derivatives by an Iridium-Catalyzed C−H Activation with Silyldimesitylborane

Direct dimesitylborylation of benzofuran derivatives by a C−H activation catalyzed by an iridium(I)/N-heterocyclic carbene (NHC) complex in the presence of Ph₂MeSi-BMes₂ afforded the corresponding dimesitylborylation products in good to high yield with excellent regioselectivity. This method provides a straightforward route to donor–(π-spacer)–acceptor systems with intriguing solvatochromic luminescence properties.     

Cobalt(III)‐Catalyzed Intramolecular Cross‐Dehydrogenative C−H/X−H Coupling: Efficient Synthesis of Indoles and Benzofurans

An efficient cobalt(III)‐catalyzed intramolecular cross‐dehydrogenative C?H/N?H coupling of ortho‐alkenylanilines has been developed utilizing O₂ as a terminal oxidant. The developed reaction tolerates various reactive functional groups and allows the synthesis of diverse indole derivatives in good to excellent yields. The method was successfully extended to the synthesis of benzofurans through the intramolecular cross‐dehydrogenative C?H/O?H coupling of ortho‐alkenylphenols.     

Synthesis,Molecular Docking,and Biofilm Formation Inhibitory Activity of Bis(Indolyl)Pyridines Analogues of the Marine Alkaloid Nortopsentin

An efficient and simple protocol for the synthesis of a new class of diverse bis(indolyl)pyridines analogues of the marine alkaloid nortopsentin has been reported. A one-pot four-component condensation of 3-cyanocarbomethylindole, various aldehyde, 3-acetylindole, and ammonium acetate in glacial acetic acid led to the formation of 2,6-bis(1H-indol-3-yl)-4-(substituted-phenyl)pyridine-5-carbonitriles. Additionally, 2,6-bis(1H-indol-3-yl)-4-(benzofuran) pyridine-5-carbonitriles were prepared via a one-pot four-component condensation of 3-cyanocarbomethylindole, various N-substituted-indole-3-aldehydes, 2-acetylbenzofuran, and ammonium acetate. The synthesized compounds were evaluated for their ability to inhibit biofilm formation against the Gram-positive bacterial reference strains Staphylococcus aureus ATCC 6538 and the Gram-negative strain Escherichia coli ATCC 25922. Some of the new compounds showed a marked selectivity against the Gram-positive and Gram-negative strains. Remarkably, five compounds 4b, 7a, 7c, 7d and 8e demonstrated good antibiofilm formation against S. aureus and E. coli. On the other hand, the release of reducing sugars and proteins from the treated bacterial strains over the untreated strains was considered to explain the disruption effect of the selected compound on the contact cells of S. aureus and E. coli. Out of all studied compounds, the binding energies and binding mode of bis-indole derivatives 7c and 7d were theoretically the best thymidylate kinase, DNA gyrase B and DNA topoisomerase IV subunit B inhibitors.     

Quantum chemical study on the mechanism of intramolecular cyclization of 2‐benzyloxyphenyl trimethylsilyl ketone to give the benzofuran derivatives

Quantum chemical calculations have been performed to explore the mechanism of intramolecular cyclization of 2‐benzyloxyphenyl trimethylsilyl ketone (acylsilane) to give the benzofuran derivatives stereoselectively. This reaction involves a formation of siloxycarbene intermediate and a C–H bond insertion of siloxycarbene. The comparative studies on three possible insertion of siloxycarbene show that the concerted insertion of siloxycarbene into C–H bond (pathway a), which needs overcoming an energy barrier of 45.1 kcal/mol, is the most unlikely pathway, and the stepwise insertion of siloxycarbene without spin multiplicity change (pathway c) is energetically more favorable than the stepwise insertion of siloxycarbene with spin multiplicity change (pathway b). More importantly, this work can provide an insight into the stereoselectivity in this reaction in atomic molecular level. The formation of siloxycarbene is calculated to be endergonic by 22.9 kcal/mol with an energy barrier of 30.2 kcal/mol, being the rate‐determining step of the whole process. Copyright © 2011 John Wiley & Sons, Ltd.     

An efficient solid‐phase synthesis of substituted benzofuran using selenium‐bound resin

A very efficient solid‐phase synthesis of substituted benzofuran using polymer‐supported selenium resin is described. The advantages of the new method are good yields, high purity, straightforward operations, broad range and high diversity of products, lack of odor, and good stability of the resins. The easy work‐up procedure makes the method suitable for building parallel libraries. Copyright © 2012 John Wiley & Sons, Ltd.     

芳并呋喃类化合物的—锅化合成法

本文报道用KF/Al_2O_3作为碱催化剂,由水杨醛或2-羟基-1-萘醛分别和α-溴代乙酸酯、α-溴代苯乙酮、苄基氯、4,4’-二氯甲基联苯和1,5-二氯甲基萘等进行一锅化缩合反应,以38～89％的产率合成了14种芳并呋喃化合物。     

微波促进下1-芳甲酰基-4-(2′-苯并呋喃甲酰基)氨基硫脲及其衍生物的合成

微波辐射条件下 ,首先由 2 苯并呋喃甲酰氯在相转移条件下依次与硫氰酸铵和芳甲酰肼反应合成了一系列 1 芳甲酰基 4 ( 2′ 苯并呋喃甲酰基 )氨基硫脲 .进一步在微波辐射的条件下由这些氨基硫脲分别与碘酸钾、醋酸或醋酸汞等试剂作用高产率地制得了 1 芳甲酰基 4 ( 2′ 苯并呋喃甲酰基 )氨基脲、2 芳基 5 ( 2′ 苯并呋喃甲酰胺基 ) 1,3 ,4 噻二唑和 2 芳基 5 ( 2′ 苯并呋喃甲酰胺基 ) 1,3 ,4 二唑 .     

Synthesis of Optically Enriched Spirocyclic Benzofuran‐2‐ones by Bifunctional Thiourea‐Base Catalyzed Double‐Michael Addition of Benzofuran‐2‐ones to Dienones

A highly enantioselective catalytic double‐Michael addition reaction of substituted benzofuran‐2‐ones with divinyl ketones promoted by readily accessible tertiary amine–thiourea Cinchona alkaloids has been developed. A number of optically enriched spirocyclic benzofuran‐2‐ones were prepared in very good yields (up to 99 %), diastereoselectivities (up to 19:1 d.r.), and very good enantioselectivities (up to 92 % ee). Density functional theory (DFT) calculations were performed to investigate the origin of stereoselectivity.     

Benzoxocin, benzoxepin and benzofuran frameworks from 5-glyco-4-nitrocyclohex-1-enes through Nef reaction and intramolecular cyclization

By treatment of sodium nitronate salts of 5-glyco-4-nitrocyclohexenes with hydrochloric acid, five new bicyclic ethers with six-membered rings fused to five-, seven-, or eight-membered rings have been synthesized; also a mechanism for their formation is proposed. Structural elucidation of the new compounds is based on spectroscopic data, as well as on their comparison with those of closely related substances.