- Design and synthesis of sinomenine isoxazole derivatives via 1,3-dipolar cycloaddition reaction
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A novel structure of sinomenine isoxazole derivatives is synthesised from sinomenine hydrochloride and aromatic aldehydes and requires six steps. 19 target compounds have been obtained in good yields. The sinomenine hydrochloride transforms to 4-alkynyl sinomenine, which is a key intermediate product to synthesise the target sinomenine isoxazole compounds, after a neutralisation reaction with ammonia and substitution reaction with 3-chloropropyne. Another key intermediate product is 1,3-dipole, which can be obtained from aromatic aldehyde. After treatment with hydroxylamine hydrochloride and then sodium carbonate solution, aromatic aldehyde is converted to aldehyde oxime, which reacts with N-chlorosuccinimide (NCS) to afford aryl hydroximino chloride. 1,3-Dipole is eventually formed in situ while triethylamine (TEA) in DMF is added dropwise. Then 4-alkynyl sinomenine is added to provide the sinomenine isoxazole derivative via 1,3-dipolar cycloaddition reaction as the key step. All the target compounds are characterised by melting point, 1H NMR, 13C NMR, HRMS and FT-IR spectroscopy.
- Pan, Hongmei,Lu, Tong,Wu, Xuedan,Gu, Chengwen,Tao, Naili,Zhang, Biao,Wang, Ao,Chen, Guangmei,Zhang, Kehua,Cheng, Jie,Jin, Jie
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supporting information
p. 2360 - 2364
(2019/11/11)
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- Dibenzazepine-linked isoxazoles: New and potent class of α-glucosidase inhibitors
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α-Glucosidase inhibition is a valid approach for controlling hyperglycemia in diabetes. In the current study, new molecules as a hybrid of isoxazole and dibenzazepine scaffolds were designed, based on their literature as antidiabetic agents. For this, a series of dibenzazepine-linked isoxazoles (33–54) was prepared using Nitrile oxide-Alkyne cycloaddition (NOAC) reaction, and evaluated for their α-glucosidase inhibitory activities to explore new hits for treatment of diabetes. Most of the compounds showed potent inhibitory potency against α-glucosidase (EC 3.2.1.20) enzyme (IC50 = 35.62 ± 1.48 to 333.30 ± 1.67 μM) using acarbose as a reference drug (IC50 = 875.75 ± 2.08 μM). Structure-activity relationship, kinetics and molecular docking studies of active isoxazoles were also determined to study enzyme-inhibitor interactions. Compounds 33, 40, 41, 46, 48–50, and 54 showed binding interactions with critical amino acid residues of α-glucosidase enzyme, such as Lys156, Ser157, Asp242, and Gln353.
- Umm-E-Farwa,Ullah, Saeed,Khan, Maria Aqeel,Zafar, Humaira,Atia-tul-Wahab,Younus, Munisaa,Choudhary, M. Iqbal,Basha, Fatima Z.
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supporting information
(2021/05/10)
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- Electrochemical synthesis of 1,2,4-oxadiazoles from amidoximes through dehydrogenative cyclization
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A convenient and efficient method for the generation of the iminoxy radical through anodic oxidation was developed for the synthesis of 3,5-disubstituted 1,2,4-oxadiazoles fromN-benzyl amidoximes. The transformation proceeds through 1.5-Hydrogen Atom Transfer (1,5-HAT) and intramolecular cyclization. The process features simple operation, mild conditions, broad substrate scope and high functional group compatibility, and provides a facile and practical way for the preparation of 1,2,4-oxadiazoles.
- Hu, Aixi,Jiang, chan,Li, mingfang,Xu, Leitao,Ye, Jiao,Yi, Yangjie
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supporting information
p. 10611 - 10616
(2021/12/27)
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- N -Oxide-Controlled Chemoselective Reduction of Nitrofuroxans
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A facile and chemoselective SnCl 2 -mediated mild reduction of regioisomeric 3- and 4-nitrofuroxans for the synthesis of aminofurazans and aminofuroxans in good yields is developed. Reduction of 4-nitrofuroxans results in the selective formation of 4-aminofuroxans, while analogous reduction of 3-nitrofuroxans affords 3-aminofurazans as a result of simultaneous reduction of the nitro group and exocyclic N-O bond.
- Fershtat, Leonid L.,Bystrov, Dmitry M.,Zhilin, Egor S.,Makhova, Nina N.
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p. 747 - 756
(2019/01/23)
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- Betulinic acid derivatives: a new class of α-glucosidase inhibitors and LPS-stimulated nitric oxide production inhibition on mouse macrophage RAW 264.7 cells
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Chemical manipulation studies were conducted on betulinic acid (1), twenty-one new rationally designed analogues of 1 with modifications at C-28 were synthesized for their evaluation of inhibitory effects on α-glucosidase and LPS-stimulated nitric oxide production in mouse macrophage RAW 264.7 cells. Compound 2 (IC50 = 5.4 μM) exhibited an almost 1.4-fold increase in α-glucosidase inhibitory activity on yeast α-glucosidase while analogues 5 (IC50 16.4 μM) and 11 (IC50 16.6 μM) exhibited a 2-fold enhanced inhibitory activity on NO-production than betulinic acid.
- Gundoju, Narayanarao,Bokam, Ramesh,Yalavarthi, Nageswara Rao,Azad, Rajaram,Ponnapalli, Mangala Gowri
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supporting information
p. 2618 - 2622
(2018/04/30)
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- Iodine Promoted One-Pot Synthesis of 2-Aryl Benzoxazoles from Amidoximes via Oxidative Cyclization and Ring Contraction
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A molecular I2-promoted one-pot synthesis of 2-aryl benzoxazoles has been developed by using amidoximes rather than the limited 2-aminophenols or 2-haloamides as substrates. The amidoxime substrates provided unique and efficient strategies for converting readily available aniline and benzaldehyde precursors into valuable chemicals. This transformation proceeded smoothly under transition-metal-free conditions through a sequential oxidative cyclization and ring contraction, and provided a potential route for introducing certain groups at any site of the scaffold.
- Zhang, Yong,Ji, Min
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supporting information
p. 7506 - 7510
(2019/11/28)
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- Tandem Condensation/Rearrangement Reaction of 2-Aminohetarene N-Oxides for the Synthesis of Hetaryl Carbamates
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A new approach to hetaryl carbamates through a tandem condensation/rearrangement reaction of 2-aminohetarene N-oxides was developed. The developed reaction is suitable for both five- and six-membered heterocycles and proceeds through the condensation of 2
- Bystrov, Dmitry M.,Zhilin, Egor S.,Fershtat, Leonid L.,Romanova, Anna A.,Ananyev, Ivan V.,Makhova, Nina N.
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supporting information
p. 3157 - 3163
(2018/08/24)
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- Preparation technology for 3-aryl-4-nitro isoxazole compound
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The invention discloses a preparation technology for a 3-aryl-4-nitro isoxazole compound. The preparation technology comprises the following steps: synthesizing a compound shown as formula II through the nucleophilic addition of hydroxylamine hydrochloride and the compound shown as formula I used as the raw material; acquiring the compound shown as formula III through the substitution reaction of the compound shown as formula II and N-chlorosuccinimide; preparing 1-dimethyl amino-2-nitro ethylene through the reaction of N,N-dimethylformamide dimethyl acetal and nitromethane used as the raw material; and acquiring a target product 3-aryl-4-nitro isoxazole compound through the cyclization reaction of the compound shown as formula III and 1-dimethyl amino-2-nitro ethylene. The raw materials in the synthesis route are low in cost and easily acquired, the operation condition is mild and is easily controlled, the product is easily purified and the preparation technology is a new method for synthesizing the 3-aryl-4-nitro isoxazole compound.
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Paragraph 0038; 0039
(2018/03/01)
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- Dimeric isoxazolyl-1,4-dihydropyridines have enhanced binding at the multi-drug resistance transporter
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A series of dimeric isoxazolyl-1,4-dihydropyridines (IDHPs) were prepared by click chemistry and examined for their ability to bind the multi-drug resistance transporter (MDR-1), a member of the ATP-binding cassette superfamily (ABC). Eight compounds in t
- Steiger, Scott A.,Li, Chun,Backos, Donald S.,Reigan, Philip,Natale
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supporting information
p. 3223 - 3234
(2017/05/29)
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- Catalytic Enantioselective [3 + 2] Cycloaddition of α-Keto Ester Enolates and Nitrile Oxides
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An enantioselective [3 + 2] cycloaddition reaction between nitrile oxides and transiently generated enolates of α-keto esters has been developed. The catalyst system was found to be compatible with in situ nitrile oxide-generation conditions. A versatile array of nitrile oxides and α-keto esters could participate in the cycloaddition, providing novel 5-hydroxy-2-isoxazolines in high chemical yield with high levels of diastereo- and enantioselectivity. Notably, the optimal reaction conditions circumvented concurrent reactions via O-imidoylation and hetero-[3 + 2] pathways.
- Bartlett, Samuel L.,Sohtome, Yoshihiro,Hashizume, Daisuke,White, Peter S.,Sawamura, Miki,Johnson, Jeffrey S.,Sodeoka, Mikiko
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supporting information
p. 8661 - 8666
(2017/07/06)
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- Cu(I) catalyzed microwave assisted telescopic synthesis of 3,5-disubstituted isoxazoles in green media
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A facile and efficient microwave assisted telescopic synthesis of diverse isoxazoles was reported in green reaction medium. Initially, N-hydroxyl imidoyl chlorides were reacted with substituted alkynes in aqueous medium using 2 mol% of [Cu(phen)(PPh3
- Meena,Maiti, Barnali,Chanda, Kaushik
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p. 5514 - 5517
(2016/11/19)
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- PHENYLISOXAZOLINE COMPOUND HAVING HERBICIDAL PROPERTIES AND USE THEREOF
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Provided are an ortho-substituted phenylisoxazoline-based compound with 2,6-difluorobenzyloxymethyl represented by Formula 1, or a racemate or enantiomer thereof, a herbicide including the ortho-substituted phenylisoxazoline-based compound, or the racemate or enantiomer thereof as an active ingredient, and a method of selectively controlling grass weed comprising treating with the ortho-substituted phenylisoxazoline-based compound, or the racemate or enantiomer thereof before or after the grass weed emerges.
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Paragraph 0032
(2014/08/20)
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- Orthogonal aerobic conversion of N-benzyl amidoximes to 1,2,4-oxadiazoles or quinazolinones
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Concise synthesis of 1,2,4-oxadiazoles was achieved by heating N-benzyl amidoximes with K3PO4 in DMF at 60°C under an O 2 atmosphere via benzylic C-H oxygenation. On the other hand, aerobic treatment of N-benzyl amidoximes
- Zhang, Feng-Lian,Wang, Yi-Feng,Chiba, Shunsuke
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supporting information
p. 6003 - 6007
(2013/09/12)
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- Synthesis of benzisoxazoles by the [3 + 2] cycloaddition of in situ generated nitrile oxides and arynes
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"Chemical Equation Presented" A variety of substituted benzisoxazoles has been prepared by the [3 + 2] cycloaddition of nitrile oxides and arynes. Both components, being highly reactive intermediates, have been generated in situ by fluoride anion from readily prepared aryne precursors and chlorooximes, The reaction scope is quite general, affording a novel, direct route to functionalized benzisoxazoles under mild reaction conditions
- Dubrovskiy, Anton V.,Larock, Richard C.
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supporting information; experimental part
p. 1180 - 1183
(2010/05/02)
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- Concise synthesis and antimicrobial activities of new substituted 5-isoxazolpenicillins
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The synthesis of a series of new 5-isoxazolpenicillins is described, which were obtained by coupling substituted isoxazoles with 6-APA. Concise large-scale synthesis of 3,5-disubstituted isoxazoles by 1,3-dipolar cycloaddition using copper(I) as catalyst was also investigated. Representative compounds were assayed for antimicrobial activities, showing satisfactory antimicrobial activities against Gram-negative bacteria.
- Wang, Xi-Zhao,Jia, Jiong,Zhang, Yan,Xu, Wei-Ren,Liu, Wei,Shi, Fang-Niu,Wang, Jian-Wu
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p. 643 - 652
(2008/03/11)
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- Facile construction and divergent transformation of polycyclic isoxazoles: Direct access to polyketide architectures
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(Matrix presented) Base-promoted cyclocondensation of C-chloro oximes with cyclic 1,3-diketones affords functionalized isoxazoles in good yield and under convenient reaction conditions. This process enables the synthesis of highly substituted products wit
- Bode, Jeffrey W.,Hachisu, Yoshifumi,Matsuura, Tomoo,Suzuki, Keisuke
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p. 391 - 394
(2007/10/03)
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- Regioselectivity in the 1,3-Dipolar Cycloaddition of Nitrile Oxides to N-(3,5-Dichlorophenyl)itaconimide
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The regioselectivity of the nitrile oxide cycloaddition with 3,3-methylene-1-(3,5-dichlorophenyl)-2,5-pyrrolidindione (1) is discussed.Arylnitrile oxides add regioselectively to the carbon-carbon double bond of 1, giving exclusively spiro-isoxazolines 3a-
- Fisera, L.,Konopikova, M.,Ertl, P.,Pronayova, N.
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p. 301 - 312
(2007/10/02)
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- Heterocycles from Nitrile Oxides. I. 5-Imino-Δ2-1,4,2-Oxathiazolines
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The reaction of some arylnitrile oxides with potassium thiocyanate in acetone at ambient temperature, has been investigated.Those having para- or meta-halo (or nitro) substituents give 3-aryl-5-imino-Δ2-1,4,2-oxathiazolines as stable cycloadducts. ortho-Substitution, on the other hand, led directly to the corresponding 5-(carbamido)imino analogues.The structures of these new heterocycles are supported by elemental analyses and spectral data.
- Hussein, Ahmed Q.,El-Abadelah, Mustafa M.,Sabri, Wail S.
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p. 301 - 304
(2007/10/02)
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