- POLYCYCLIC AMIDES AS UBE2K MODULATORS FOR TREATING CANCER
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Provided are compounds of Formula (I) and pharmaceutically acceptable salts and compositions thereof, which are useful for treating conditions associated with modulation of UBE2K.
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Paragraph 0078-0080
(2021/07/10)
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- Antibacterial and Antiviral Activities of 1,3,4-Oxadiazole Thioether 4H-Chromen-4-one Derivatives
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Various 1,3,4-oxadiazole thioether 4H-chromen-4-one derivatives were conceived. The title compounds demonstrated striking inhibitory effects againstXac,Psa, andXoo. EC50data exhibited that A8 (19.7 μg/mL) had better antibacterial activity againstXoothan myricetin, BT, and TC. Simultaneously, the mechanism of action of A8 had been verified by SEM. The results of anti-tobacco mosaic virus indicated that A9 had the bestin vivoantiviral effect compared with ningnanmycin. From the data of MST, it could be seen that A9 (0.003 ± 0.001 μmol/L) exhibited a strong binding capacity, which was far superior to ningnanmycin (2.726 ± 1.301 μmol/L). This study shows that the 1,3,4-oxadiazole thioether 4H-chromen-4-one derivatives may become agricultural drugs with great potential.
- Cao, Xiao,Liu, Fang,Liu, Liwei,Liu, Tingting,Peng, Feng,Wang, Qifan,Xie, Chengwei,Xue, Wei,Yang, Jinsong
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p. 11085 - 11094
(2021/10/01)
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- Development of phenyltriazole thiol-based derivatives as highly potent inhibitors of DCN1-UBC12 interaction
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Defective in cullin neddylation 1(DCN1) is a co-E3 ligase that is important for cullin neddylation. Dysregulation of DCN1 highly correlates with the development of various cancers. Herein, from the initial high-throughput screening, a novel hit compound 5a containing a phenyltriazole thiol core (IC50 value of 0.95 μM for DCN1-UBC12 interaction) was discovered. Further structure-based optimization leads to the development of SK-464 (IC50 value of 26 nM). We found that SK-464 not only directly bound to DCN1 in vitro, but also engaged cellular DCN1, suppressed the neddylation of cullin3, and hindered the migration and invasion of two DCN1-overexpressed squamous carcinoma cell lines (KYSE70 and H2170). These findings indicate that SK-464 may be a novel lead compound targeting DCN1-UBC12 interaction.
- Zhou, Wenjuan,Xu, Chenhao,Dong, Guanjun,Qiao, Hui,Yang, Jing,Liu, Hongmin,Ding, Lina,Sun, Kai,Zhao, Wen
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- Ultrafine Copper Oxide Particles Dispersed on Nitrogen-Doped Hollow Carbon Nanospheres for Oxidative Esterification of Biomass-Derived 5-Hydroxymethylfurfural
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One-pot synthesis of furan-2,5-dimethylcarboxylate (FDMC) from 5-hydroxymethylfurfural (HMF) is highly demanding for the commercial production of polyethylene furanoate (PEF). Herein, a direct synthesis of FDMC is reported from oxidative esterification of HMF using ultrafine CuO particles dispersed on nitrogen-doped hollow carbon nanospheres (CuO/N?C?HNSs) as a catalyst and tert-butyl hydroperoxide (TBHP) as an oxidizing and methylating reagent. The CuO/N?C?HNSs was prepared through a template protection-sacrifice strategy using SiO2 as a sacrificial template and histidine as the precursor for N and C. N-doping facilitated a strong interaction between the support and copper species, affording formation of CuO nanoparticles of less than 10 nm in size. By virtue of the highly dispersed CuO nanoparticles and a high BET surface area 373 m2/g, the CuO/N?C?HNSsshows excellent catalytic performance in the selective conversion of HMF into FDMC affording 93 % yield of the desired product with a TON value of 49. Furthermore, the oxidative esterification involving SP3C?H bond functionalization is also demonstrated using the same catalyst.
- Gupta, Shyam Sunder R.,Vinu, Ajayan,Kantam, Mannepalli Lakshmi
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p. 259 - 269
(2021/03/01)
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- Oxidative esterification of alcohols by a single-side organically decorated Anderson-type chrome-based catalyst
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The direct esterification of alcohols with non-noble metal-based catalytic systems faces great challenges. Here, we report a new chrome-based catalyst stabilized by a single pentaerythritol decorated Anderson-type polyoxometalate, [N(C4H9)4]3[CrMo6O18(OH)3C{(OCH2)3CH2OH}], which can realize the efficient transformation from alcohols to esters by H2O2oxidation in good yields and high selectivity without extra organic ligands. A variety of alcohols with different functionalities including some natural products and pharmaceutical intermediates are tolerated in this system. The chrome-based catalyst can be recycled several times and still keep the original configuration and catalytic activity. We also propose a reasonable catalytic mechanism and prove the potential for industrial applications.
- Wang, Jingjing,Jiang, Feng,Tao, Chaofu,Yu, Han,Ruhlmann, Laurent,Wei, Yongge
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supporting information
p. 2652 - 2657
(2021/04/21)
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- Rh-Catalyzed Asymmetric Hydrogenation of α,β- and β,β-Disubstituted Unsaturated Boronate Esters
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A highly enantioselective hydrogenation of α,β-unsaturated boronate esters catalyzed by Rh-(S)-DTBM-Segphos complex has been developed. Both (Z)-α,β- and β,β-disubstituted substrates can be successfully hydrogenated to afford chiral boronates with excellent enantioselectivities, up to 98 % ee. Furthermore, the obtained chiral boronate esters, as important versatile synthetic intermediates are successfully transformed to the corresponding chiral alcohols, amines and other important derivatives with maintained enantioselectivities.
- Hou, Guohua,Shen, Xin,Yan, Qiaozhi,Zi, Guofu
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supporting information
(2020/05/08)
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- DHODH INHIBITORS AND THEIR USE AS ANTIVIRAL AGENTS
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The present invention relates to a compound, or a dimer or a pharmaceutically acceptable salt or solvate of said compound or dimer, for use in a method for the treatment of a disease, disorder or condition caused by an RNA virus, said compound having the general structure shown in Formula (I).
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Page/Page column 56
(2020/11/22)
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- Synthesis, biological evaluation of benzothiazole derivatives bearing a 1,3,4-oxadiazole moiety as potential anti-oxidant and anti-inflammatory agents
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Twenty benzothiazole derivatives bearing a 1,3,4-oxadiazole moiety were synthesized and evaluated for their anti-oxidant and anti-inflammatory activities. Among these compounds, 8h and 8l were appeared to have high radical scavenging efficacies as 0.05 ± 0.02 and 0.07 ± 0.03 mmol/L of IC50 values in ABTS+[rad] bioassay, respectively. In anti-inflammatory tests, compound 8h displayed good activity with 57.35% inhibition after intraperitoneal administration, which was more potent than the reference drug (indomethacin). Molecular modeling studies were performed to investigate the binding mode of the representative compound 8h into COX-2 enzyme. In vitro enzyme study implied that compound 8h exerted its anti-inflammatory activity through COX-2 inhibition.
- Bai, Xue-Qian,Cui, Ming-Yue,Li, Chun-Shi,Liang, Cheng-Wu,Song, Ze-Wen,Wang, Hui-Yan,Zhang, Tian-Yi,Zheng, Xian-Jing
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- Discovery of [1,2,4]triazole derivatives as new metallo-β-lactamase inhibitors
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The emergence and spread of metallo-β-lactamase (MBL)-mediated resistance to β-lactam antibacterials has already threatened the global public health. A clinically useful MBL inhibitor that can reverse β-lactam resistance has not been established yet. We here report a series of [1,2,4]triazole derivatives and analogs, which displayed inhibition to the clinically relevant subclass B1 (Verona integron-encoded MBL-2) VIM-2. 3-(4-Bromophenyl)-6,7-dihydro-5H-[1,2,4]triazolo [3,4-b][1,3]thiazine (5l) manifested the most potent inhibition with an IC50 (half-maximal inhibitory concentration) value of 38.36 μM. Investigations of 5l against other B1 MBLs and the serine β-lactamases (SBLs) revealed the selectivity to VIM-2. Molecular docking analyses suggested that 5l bound to the VIM-2 active site via the triazole involving zinc coordination and made hydrophobic interactions with the residues Phe61 and Tyr67 on the flexible L1 loop. This work provided new triazole-based MBL inhibitors and may aid efforts to develop new types of inhibitors combating MBL-mediated resistance.
- Yuan, Chen,Yan, Jie,Song, Chen,Yang, Fan,Li, Chao,Wang, Cheng,Su, Huiling,Chen, Wei,Wang, Lijiao,Wang, Zhouyu,Qian, Shan,Yang, Lingling
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- Visible-light-induced selective aerobic oxidation of sp3 C-H bonds catalyzed by a heterogeneous AgI/BiVO4 catalyst
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An efficient oxidation of sp3 C-H bonds to esters and ketones has been developed using AgI/BiVO4 as the photocatalyst and O2 as the oxidant in water. Various substrates can be transformed into the desired esters and ketones in moderate to good yields. The synthetic utility of this approach has been demonstrated by gram-level experiments and consecutive oxidation experiments. A plausible mechanism has been proposed.
- Jiang, Li-Ya,Ming, Jing-Jing,Wang, Lian-Yue,Jiang, Yuan-Yuan,Ren, Lan-Hui,Wang, Zi-Cheng,Cheng, Wen-Chen
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supporting information
p. 1156 - 1163
(2020/03/11)
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- Copper-catalyzed oxidative methyl-esterification of 5-hydroxymethylfurfural using TBHP as an oxidizing and methylating reagent: A new approach for the synthesis of furan-2,5-dimethylcarboxylate
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Catalytic conversion of 5-hydroxymethylfurfural (HMF) into furan-2,5-dimethylcarboxylate (FDMC) is of great significance in the production of polyethylene furanoate (PEF), a renewable biomass-derived polymer that can replace the fossil dependent polyethylene terephthalate (PET). Herein, for the first time, we report the synthesis of FDMC from oxidative methyl-esterification of HMF using tert-butyl hydroperoxide (TBHP) as an oxidizing and methylating reagent catalyzed by mesoporous alumina nanospheres-embedded with CuO nanoparticles (CuO/m-Al2O3). The CuO/m-Al2O3 catalysts with different copper contents were prepared by evaporation-induced self-assembly of a structure-directing agent (Pluronic P-123). The decomposition of P-123 during calcination in air results into the formation of a mesoporous structure with highly dispersed CuO nanoparticles. The as-prepared 6-CuO/m-Al2O3 exhibits excellent catalytic activity towards oxidative methyl-esterification of HMF into FDMC with 92% yield and turnover frequency (TOF) of 0.56 h?1. Furthermore, oxidative methyl-esterification of a range of substrates through SP3 C[sbnd]H bond functionalization has also been demonstrated using the same catalyst.
- Gupta, Shyam Sunder R.,Kantam, Mannepalli Lakshmi,Vinu, Ajayan
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p. 259 - 269
(2020/06/27)
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- Development of novel liver?X?receptor modulators based on a 1,2,4-triazole scaffold
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Liver X Receptor (LXR) agonists have been reported as a potential treatment for atherosclerosis, Alzheimer's disease and hepatitis C virus (HCV) infection. We have designed and synthesized a series of potent compounds based on a 1,2,4-triazole scaffold as novel LXR modulators. In cell-based cotransfection assays these compounds generally functioned as LXR agonists and we observed compounds with selectivity towards LXRα (7-fold) and LXRβ (7-fold) in terms of potency. Assessment of the effects of selected compounds on LXR target gene expression in HepG2 cells revealed that compounds 6a-b and 8a-b behaved as inverse agonists on FASN expression even though they were agonists in the LXRα and LXRβ cotransfection assays. Interestingly, these compounds had no effect on the expression of SREBP-1c confirming a unique LXR modulator pharmacology. Molecular docking studies and evaluation of ADME properties in-silico show that active compounds possess favorable binding modes and ADME profiles. Thus, these compounds may be useful for in vivo characterization of LXR modulators with unique profiles and determination of their potential clinical utility.
- Goher, Shaimaa S.,Griffett, Kristine,Hegazy, Lamees,Elagawany, Mohamed,Arief, Mohamed M.H.,Avdagic, Amer,Banerjee, Subhashis,Burris, Thomas P.,Elgendy, Bahaa
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supporting information
p. 449 - 453
(2019/01/04)
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- Electrochemical Reductive Smiles Rearrangement for C-N Bond Formation
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A conceptually new and synthetically valuable radical Smiles rearrangement reaction is reported under undivided electrolytic conditions. This protocol employs an entirely new strategy for the electrochemical radical Smiles rearrangement. Remarkably, an amidyl radical generated from the cleavage of the N-O bond under reductive electrolytic conditions plays a crucial role in this transformation. Various hydroxylamine derivatives bearing different substituents are suitable in this electrochemical transformation, furnishing the corresponding amides in up to 86% yield.
- Chang, Xihao,Zhang, Qinglin,Guo, Chang
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supporting information
p. 10 - 13
(2019/01/04)
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- Nickel-catalyzed regioselective C-H halogenation of electron-deficient arenes
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A straightforward Ni(ii)-catalyzed general strategy was developed for the ortho-halogenation of electron-deficient arenes with easily available halogenating reagents N-halosuccinimides (NXS; X = Br, Cl and I). The transformation was highly regioselective and a wide substrate scope and functional group tolerance were observed. This discovery could be of great significance for the selective halogenation of amides, benzoic esters and other substances with guiding groups. Mechanistic investigations were also described.
- Li, Ze-Lin,Wu, Peng-Yu,Cai, Chun
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supporting information
p. 3462 - 3468
(2019/02/25)
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- Efficient synthesis of esters through oxone-catalyzed dehydrogenation of carboxylic acids and alcohols
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Since esters are important organic synthesis intermediates, an environmentally friendly oxone catalyzed-esterification of carboxylic acids with alcohols has been developed. A series of carboxylic acid esters are obtained in high yield. This strategy requires mild reaction conditions, providing an attractive alternative for the construction of valuable carbonyl esters. Electron-rich and electron-deficient groups are compatible with the standard conditions and a variety of substrates are demonstrated. Moreover, the reaction could easily be adapted to typical prodrugs, drugs and gram-scale synthesis.
- Hou, Fei,Wang, Xi-Cun,Quan, Zheng-Jun
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supporting information
p. 9472 - 9476
(2019/01/03)
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- Exploration of Biaryl Carboxylic Acids as Proton Shuttles for the Selective Functionalization of Indole C-H Bonds
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A survey of diversely substituted 2-arylbenzoic acids were synthesized and tested for use as proton shuttle in the direct arylation of indoles with bromobenzenes. It was found that 3-ethoxy-2-phenylbenzoic acid gives superior yield and selectivity for this class of substrates.
- Pi, Jing-Jing,Lu, Xiao-Yu,Liu, Jing-Hui,Lu, Xi,Xiao, Bin,Fu, Yao,Guimond, Nicolas
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p. 5791 - 5800
(2018/05/14)
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- A biocatalytic method for the chemoselective aerobic oxidation of aldehydes to carboxylic acids
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Herein, we present a study on the oxidation of aldehydes to carboxylic acids using three recombinant aldehyde dehydrogenases (ALDHs). The ALDHs were used in purified form with a nicotinamide oxidase (NOx), which recycles the catalytic NAD+ at the expense of dioxygen (air at atmospheric pressure). The reaction was studied also with lyophilised whole cell as well as resting cell biocatalysts for more convenient practical application. The optimised biocatalytic oxidation runs in phosphate buffer at pH 8.5 and at 40 °C. From a set of sixty-one aliphatic, aryl-Aliphatic, benzylic, hetero-Aromatic and bicyclic aldehydes, fifty were converted with elevated yield (up to >99%). The exceptions were a few ortho-substituted benzaldehydes, bicyclic heteroaromatic aldehydes and 2-phenylpropanal. In all cases, the expected carboxylic acid was shown to be the only product (>99% chemoselectivity). Other oxidisable functionalities within the same molecule (e.g. hydroxyl, alkene, and heteroaromatic nitrogen or sulphur atoms) remained untouched. The reaction was scaled for the oxidation of 5-(hydroxymethyl)furfural (2 g), a bio-based starting material, to afford 5-(hydroxymethyl)furoic acid in 61% isolated yield. The new biocatalytic method avoids the use of toxic or unsafe oxidants, strong acids or bases, or undesired solvents. It shows applicability across a wide range of substrates, and retains perfect chemoselectivity. Alternative oxidisable groups were not converted, and other classical side-reactions (e.g. halogenation of unsaturated functionalities, Dakin-Type oxidation) did not occur. In comparison to other established enzymatic methods such as the use of oxidases (where the concomitant oxidation of alcohols and aldehydes is common), ALDHs offer greatly improved selectivity.
- Knaus, Tanja,Tseliou, Vasilis,Humphreys, Luke D.,Scrutton, Nigel S.,Mutti, Francesco G.
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p. 3931 - 3943
(2018/09/11)
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- Visible light mediated oxidation of benzylic sp3 C-H bonds using catalytic 1,4-hydroquinone, or its biorenewable glucoside, arbutin, as a pre-oxidant
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Benzylic ethers undergo a visible light induced C-H activation and oxygen insertion to give the corresponding benzoate esters in moderate to good yields. The conditions employ substoichiometric amounts of 1,4-hydroquinone with copper(ii) chloride dihydrate as an electron-transfer mediator, oxygen as the terminal oxidant and dimethyl carbonate as solvent under visible light irradiation. The naturally occurring glucoside, arbutin, which is commercially available or can be accessed via extraction of the leaves of bearberry (Arctostaphylos uva-ursi) or elephant ears (Bergenia crassifolia) can be used as a biorenewable source of 1,4-hydroquinone. The methodology exploits the increase in oxidizing ability of quinones upon irradiation with visible light, and offers a sustainable alternative for the late stage oxidative functionalization of benzylic C-H bonds. It is applicable to a range of cyclic benzylic ethers such as isochromans and phthalans, and simple benzyl alkyl ethers. It can also be applied in the oxidation of benzylic amines into amides, and of diarylmethanes into the corresponding ketones. Mechanistic studies suggest that the reaction proceeds by H-abstraction by the photo-excited triplet benzoquinone to give a benzylic radical that subsequently reacts with molecular oxygen.
- Finney, Laura C.,Mitchell, Lorna J.,Moody, Christopher J.
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supporting information
p. 2242 - 2249
(2018/05/28)
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- Fluorene-based organic compound and application thereof on OLED device
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The invention relates to a fluorene-based organic compound and application thereof on an OLED device. A structure of the compound is that fluorine is connected with a hexatomic ring structure of a benzo hexatomic ring through a carbon-carbon bond, so that material chemical stability is improved and active positions of a branch chain radical are prevented from being exposed through the carbon-carbon bond connection; the whole molecule is a relatively great rigid structure, and has relatively high triplet-state energy level (T1); moreover, steric hindrance is great, rotation is not liable to occur and the three-dimensional space structure is more stable, so that the compound has a relatively high glass transition temperature and relatively high molecule thermal stability; besides, distribution positions of HOMO and LUMO of the compound are separated from each other, so that the fluorene-based organic compound has proper HOMO and LUMO energy level; and after the compound is applied to theOLED device, light-emitting efficiency of the device can be effectively improved, and the service life of the device can be effectively prolonged.
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-
Paragraph 0082; 0084; 0085
(2018/03/26)
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- PROCESS FOR THE PREPARATION OF ORGANIC BROMIDES
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The present invention provides a process for the preparation of organic bromides, by a radical bromodecarboxylation of carboxylic acids with a bromoisocyanurate.
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Paragraph 00139; 00141; 00157
(2017/07/28)
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- HEPATITIS B CORE PROTEIN MODULATORS
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The present disclosure provides, in part, compounds having allosteric effector properties against Hepatitis B virus Cp. Also provided herein are methods of treating viral infections, such as hepatitis B, comprising administering to a patient in need thereof a disclosed compound.
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-
Paragraph 00091
(2017/04/11)
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- Design, synthesis, and negative inotropic evaluation of 4-phenyl-1H-1,2,4-triazol-5(4H)-one derivatives containing triazole or piperazine moieties
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In this study, four novel series of 4-phenyl-1H-1,2,4-triazol-5(4H)-one derivatives containing triazole or piperazine moieties were designed, synthesized, and evaluated for negative inotropic activity by measuring the left atrium stroke volume in isolated rabbit heart preparations. Almost all of the compounds showed an ability to moderate the cardiac workload by decreasing the heart rate and contractility. Among them, 7h was found to be the most potent with a change in stroke volume of ?48.22?±?0.36% at a concentration of 3?×?10?5?mol/L (metoprolol: ?9.74?±?0.14%). The cytotoxicity of these compounds was evaluated using the human cervical cancer cell line HeLa, the liver cancer cell line Hep3B, and the human normal hepatic cell line LO2. A preliminary study of the mechanism of action for the compound 7h on the regulation of atrial dynamics with ATP-sensitive K+ channel and L-type Ca2+ channel blockers glibenclamide and nifedipine was performed in the isolated perfused beating rabbit atria.
- Wei, Zhi-Yu,Cui, Bai-Ri,Cui, Xun,Wu, Yan-Ling,Fu, Yang,Liu, Li-Ping,Piao, Hu-Ri
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- Preparation of phthalates via carbonylation of o-dibromobenzenes in solutions of Pd catalysts and reactivity of Ar?Br bonds
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Carbonylation of o-dibromobenzene and its derivatives in the presence of palladium phosphine complexes with NaOAc or Et3N additive leads to the formation of phthalates in high yield under mild conditions. Correlation NMR spectroscopy data and s
- Elman,Perepukhov,Ovsyannikova,Maksimychev
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p. 2269 - 2275
(2017/11/24)
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- Oxalic acid as the: In situ carbon monoxide generator in palladium-catalyzed hydroxycarbonylation of arylhalides
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An efficient palladium-catalyzed hydroxycarbonylation reaction of arylhalides using oxalic acid as a CO source has been developed. The reaction features high safety, low catalyst loading, and a broad substrate scope, and provides a safe and tractable approach to access a variety of aromatic carboxylic acid compounds. Mechanistic studies revealed the decomposition pattern of oxalic acid.
- Shao, Changdong,Lu, Ailan,Wang, Xiaoling,Zhou, Bo,Guan, Xiaohong,Zhang, Yanghui
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p. 5033 - 5040
(2017/07/10)
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- Formation, Oxidation, and Fate of the Breslow Intermediate in the N-Heterocyclic Carbene-Catalyzed Aerobic Oxidation of Aldehydes
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The reaction paths and intermediate structures related to the formation of the Breslow intermediate and its oxidation along the oxidative/oxygenative lanes have been studied from a mechanistic point of view, with the support of gas-phase and computational studies. The results confirm the occurrence of a single-electron transfer from the Breslow intermediate to the molecular oxygen with formation of a radical couple that recombines either as a peroxide anion 7′ to afford the aldehyde-to-carboxylic acid product or as a hydroperoxy derivative 7″ that evolved into an electrophilic acyl azolium, opening to the aldehyde-to-ester conversion. Steric factors enter into determining the different reactivity. All of the intermediates of both catalytic paths have been observed and characterized under mass spectrometric conditions. In particular, for the imidazoline catalyst, the (+)ESI-MS/(MS) detection of the genuine Breslow intermediate was made possible in virtue of its limited reactivity. Mechanistic aspects of the N-heterocyclic carbenes catalyzed aerobic oxidation of aldehydes shares important similarities with that one of the recently revisited benzoin condensation.
- Bortolini, Olga,Chiappe, Cinzia,Fogagnolo, Marco,Massi, Alessandro,Pomelli, Christian Silvio
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p. 302 - 312
(2017/04/26)
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- Heterogeneous cobalt catalysts for selective oxygenation of alcohols to aldehydes, esters and nitriles
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Efficient and green oxygenation of alcohols to the corresponding aldehydes, esters and nitriles was developed with high selectivity. Functional alcohols, including some heterocyclic and allylic alcohols can be oxygenated to the corresponding aldehydes, esters and nitriles respectively. Moreover, the catalyst can be recycled and reused without significant deactivation. Noteworthy, the Co@NC (800-2h) catalyzed oxygenation of alcohols can be regulated easily by changing the reaction conditions, and then the corresponding aldehydes, esters and nitriles can be obtained in high yields respectively.
- Mao, Fei,Qi, Zhengliang,Fan, Haipeng,Sui, Dejun,Chen, Rizhi,Huang, Jun
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p. 1498 - 1503
(2017/01/18)
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- Copper-Catalyzed Amino Lactonization and Amino Oxygenation of Alkenes Using O-Benzoylhydroxylamines
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A copper-catalyzed amino lactonization of unsaturated carboxylic acids has been achieved as well as the analogous intermolecular three-component amino oxygenation of olefins. The transformation features mild conditions and a remarkably broad substrate sco
- Hemric, Brett N.,Shen, Kun,Wang, Qiu
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supporting information
p. 5813 - 5816
(2016/06/09)
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- Indium-Catalyzed Reductive Sulfidation of Esters by Using Thiols: An Approach to the Diverse Synthesis of Sulfides
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A new reductive preparation of unsymmetrical sulfides from esters and thiols in the presence of InI3 and either 1,1,3,3-tetramethyldisiloxane (TMDS) or PhSiH3 as the reductant was developed. This protocol was applied to not only benzoic acid esters that have a methoxy, methyl, chloro, bromo, iodo, or trifluoromethyl group on the aromatic ring but also aliphatic acid esters with either aromatic or aliphatic thiols. A reaction mechanism is proposed by using Hammett plot results and several control experiments. The reductive preparation of unsymmetrical sulfides from esters and thiols by using InI3 and either 1,1,3,3-tetramethyldisiloxane (TMDS) or PhSiH3 was developed. Several mechanistic studies support that the present transformation proceeds through O,S-and S,S-acetals as the reaction intermediates. TMDS = 1,1,3,3-tetramethyldisiloxane, R = aliphatic group.
- Miyazaki, Takahiro,Kasai, Shinsei,Ogiwara, Yohei,Sakai, Norio
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supporting information
p. 1043 - 1049
(2016/03/01)
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- Formation of substituted 1-naphthols and related products via dimerization of alkyl 3-(o-halo(het)aryl)-oxopropanoates based on a CuI-catalyzed domino C-arylation/condensation/aromatization process
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Substrates bearing both a β-ketoester moiety and a (het)aryl halide structure element were dimerized to 1-naphthols and related products in the presence of catalytic amounts of CuI in isopropanol. The reaction starts with an intermolecular C-arylation, which is followed by an intramolecular condensation. The final aromatization delivers the highly substituted products with yields up to 81%.
- Weischedel, Heike,Sudheendran, Kavitha,Mikhael, Alevtina,Conrad, Jürgen,Frey, Wolfgang,Beifuss, Uwe
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p. 3454 - 3467
(2016/06/06)
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- Design, synthesis and antibacterial activity of isatin derivatives as FtsZ inhibitors
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Seven isatin derivatives have been designed, and their chemical structures were characterized by single crystal X-ray diffraction studies, 1H NMR, MS, and elemental analysis. Structural stabilization followed by intramolecular as well as intermolecular H-bonds makes these molecules as perfect examples in molecular recognition with self-complementary donor and acceptor units within a single molecule. These compounds were evaluated for antimicrobial activities. Docking simulations have been performed to position compounds into the FtsZ active site to determine their probable binding models. All of the compounds exhibited better antibacterial activities. Interestingly, compound 5c and 5d exhibited better antibacterial activities with IC50 values of 0.03 and 0.05 μmol/mL against Staphylococcus aureus, respectively. Compound 5g displays antibacterial activity with IC50 values of 0.672 and 0.830 μmol/mL against Escherichia coli and Pseudomonas aeruginosa, respectively.
- Lian, Zhi-Min,Sun, Juan,Zhu, Hai-Liang
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-
- An enantioselective formal synthesis of montelukast sodium
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A formal synthesis of the antiasthma drug montelukast sodium is described, wherein the key chiral diol intermediate was accessed with greater convergence of the C-C bond-forming steps as compared to previous routes. Improved synthetic efficiency was achie
- Bollikonda, Satyanarayana,Mohanarangam, Saravanan,Jinna, Rajender Reddy,Kandirelli, Venkata Kiran Kumar,Makthala, Laxman,Sen, Saikat,Chaplin, David A.,Lloyd, Richard C.,Mahoney, Thomas,Dahanukar, Vilas Hareshwar,Oruganti, Srinivas,Fox, Martin E.
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p. 3891 - 3901
(2015/06/02)
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- NOVEL BIPHENYL DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, AND PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING INFLAMMATORY DISEASES OR AUTOIMMUNE DISEASES COMPRISING THE SAME AS ACTIVE INGREDIENT
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The present invention relates to a novel biphenyl derivative or a pharmaceutically acceptable salt thereof, a pharmaceutical composition for preventing or treating inflammatory diseases or autoimmune diseases comprising the same as an active ingredient, and methods for treating inflammatory disease or autoimmune diseases with the pharmaceutical composition. Novel biphenyl derivatives according to the present invention promote the phagocytosis of macrophages and inhibit the chemotaxis to exhibit excellent inflammation terminating and anti-inflammatory effects and thus can be effectively used as therapeutic agents for inflammatory diseases or autoimmune diseases.
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-
Paragraph 66
(2015/11/18)
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- Electronic effects on the substitution reactions of benzhydrols and fluorenyl alcohols. Determination of mechanism and effects of antiaromaticity
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A range of substituted benzhydrols and fluorenols were prepared and subjected to acid catalysed methanolysis. Analysis of the rates of each of these processes showed correlation with Hammett σ+ parameters as is consistent with the significant build-up of positive charge adjacent to the ring. In combination with the similarity of the electronic susceptibility of the processes, these data suggest that both reactions proceed through a unimolecular rate-determining step. This shows that the effect of fusion of the phenyl systems (and hence potentially introducing an antiaromatic carbocation intermediate) is only to slow the rate of reaction rather than change the mechanism of the process.
- George, Stephen R. D.,Elton, Timothy E.,Harper, Jason B.
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supporting information
p. 10745 - 10750
(2015/11/17)
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- Synthesis, anti-HIV activity and Molecular modeling study of 3-aryl-6-adamantylmethyl-[1,2,4] triazolo[3,4-b][1,3,4]thiadiazole derivatives
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A series of novel 3-aryl-6-adamantylmethyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles 6a-l were synthesized by a simple method with the aim of developing novel HIV non-nucleoside reverse transcriptase inhibitors. All the synthesized compounds were structurally confirmed by spectral analyses. The structure of 6a was unambiguously verified by X-ray structure determination. The synthesized compounds were evaluated for their anti-HIV activity and four analogs displayed moderate inhibitory activity with EC50 values ranging from 10.10 to 12.40 μg mL-1. Molecular docking of 6g with HIV-1 reverse transcriptase was studied to rationalize some structureactivity relationships (SARs).
- Khan, Mahmood-Ul-Hassan,Hameed, Shahid,Farman, Muhammad,Al-Masoudia, Najim A.,Stoeckli-Evans, Helen
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p. 609 - 616
(2016/02/18)
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- Nitrogen enriched mesoporous organic polymer anchored copper(ii) material: An efficient and reusable catalyst for the synthesis of esters and amides from aromatic systems
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A new copper-grafted mesoporous poly-melamine-formaldehyde (Cu-mPMF) has been synthesized from melamine and paraformaldehyde in DMSO medium, followed by grafting of Cu(ii) at its surface. Cu-mPMF has been characterized by elemental analysis, powder XRD, HR TEM, FE-SEM, N2 adsorption study, FT-IR, UV-vis DRS, TGA-DTA, EPR spectroscopy, Raman spectroscopy and X-ray photoelectron spectroscopy (XPS). The Cu-grafted mesoporous material showed very good catalytic activity in methyl esterification of benzylic alcohols and amidation of nitriles. Moreover, the catalyst is easily recoverable and can be reused seven times without appreciable loss of catalytic activity in the above reactions. The highly dispersed and strongly bound Cu(ii) sites in the Cu-grafted mesoporous polymer could be responsible for the observed high activities of the Cu-mPMF catalyst. Due to strong binding with the functional groups of the polymer, no evidence of leached copper from the catalyst during the course of reaction emerged, suggesting true heterogeneity in the catalytic process. This journal is
- Molla, Rostam Ali,Iqubal, Md. Asif,Ghosh, Kajari,Kamaluddin,Islam, Sk. Manirul
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p. 6546 - 6559
(2015/04/14)
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- Magnetic Co3O4/reduced graphene oxide nanocomposite as a superior heterogeneous catalyst for one-pot oxidative esterification of aldehydes to methyl esters
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A magnetically separable hybrid material consisting of Co3O4 nanoparticles supported on reduced graphene oxide (Co3O4/rGO) was synthesized through a simple co-reduction process of graphene oxide (GO) and cobalt chloride (CoCl2) using sodium borohydride (NaBH4). The Co3O4/rGO heterogeneous catalyst exhibited a high-performance for the oxidative esterification of aldehydes to the corresponding methyl esters using tert-butyl hydroperoxide (TBHP) as an oxidant. Owing to the synergistic effect of rGO support, the hybrid catalyst exhibited superior catalytic activity to the corresponding cobalt oxide catalyst. Importantly, the synthesized hybrid possesses good magnetic properties, which enable facile recovery of the catalyst by using an external magnet.
- Panwar, Vineeta,Al-Nafiey, Amer,Addad, Ahmed,Sieber, Brigitte,Roussel, Pascal,Boukherroub, Rabah,Jain, Suman L.
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p. 88567 - 88573
(2015/11/09)
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- Characterization of a novel multifunctional resveratrol derivative for the treatment of atrial fibrillation
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Background and Purpose Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with an increased risk for stroke, heart failure and cardiovascular-related mortality. Candidate targets for anti-AF drugs include a potassium channel Kv1.5, and the ionic currents I KACh and late INa, along with increased oxidative stress and activation of NFAT-mediated gene transcription. As pharmacological management of AF is currently suboptimal, we have designed and characterized a multifunctional small molecule, compound 1 (C1), to target these ion channels and pathways. Experimental Approach We made whole-cell patch-clamp recordings of recombinant ion channels, human atrial IKur, rat atrial I KACh, cellular recordings of contractility and calcium transient measurements in tsA201 cells, human atrial samples and rat myocytes. We also used a model of inducible AF in dogs. Key Results C1 inhibited human peak and late Kv1.5 currents, frequency-dependently, with IC50 of 0.36 and 0.11 μmol·L-1 respectively. C1 inhibited I KACh (IC50 of 1.9 μmol·L-1) and the Nav1.5 sodium channel current (IC50s of 3 and 1 μmol·L-1 for peak and late components respectively). C1 (1 μmol·L-1) significantly delayed contractile and calcium dysfunction in rat ventricular myocytes treated with 3 nmol·L -1 sea anemone toxin (ATX-II). C1 weakly inhibited the hERG channel and maintained antioxidant and NFAT-inhibitory properties comparable to the parent molecule, resveratrol. In a model of inducible AF in conscious dogs, C1 (1 mg·kg-1) reduced the average and total AF duration. Conclusion and Implications C1 behaved as a promising multifunctional small molecule targeting a number of key pathways involved in AF.
- Baczko, Istvan,Liknes, David,Yang, Wei,Hamming, Kevin C.,Searle, Gavin,Jaeger, Kristian,Husti, Zoltan,Juhasz, Viktor,Klausz, Gergely,Pap, Robert,Saghy, Laszlo,Varro, Andras,Dolinsky, Vernon,Wang, Shaohua,Rauniyar, Vivek,Hall, Dennis,Dyck, Jason R.B.,Light, Peter E.
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supporting information
p. 92 - 106
(2014/01/06)
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- RESVERATROL ANALOGS AND THERAPEUTIC USES THEREOF
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Resveratrol analogs and their use to inhibit Kv1.5 channels are provided. The resveratrol analogs are useful in the treatment of atrial arrhythmias, including atrial fibrillation (AF). Exemplary resveratrol analogs are compounds of general Formula (I):
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Paragraph 00184
(2014/12/12)
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- Ti/Ni-mediated inter- and intramolecular conjugate addition of aryl and alkenyl halides and triflates
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In this work, we show that the unique combination of a nickel catalyst and Cp2TiCl allows the direct conjugate addition of aryl and alkenyl iodides, bromides, and to a lesser extent, chlorides and triflates to α,β-unsaturated carbonyls at room temperature, without requiring the previous formation of an organometallic nucleophile. The reaction proceeds inter- and intramolecularly with good functional group compatibility, which is key for the development of free protecting group methodologies. Carbo- and heterocycles of five- and six-membered rings are obtained in good yields. Moreover, some insights about the mechanism involved have been obtained from cyclic voltammetry, UV-vis, and HRTEM measurements.
- Marquez, Irene R.,Miguel, Delia,Millan, Alba,Marcos, M. Luisa,De Cienfuegos, Luis Alvarez,Campana, Araceli G.,Cuerva, Juan M.
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p. 1529 - 1541
(2014/03/21)
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- Synthesis and evaluation of novel azoles as potent antifungal agents
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Using a rational approach to the design of antifungal agents, a series of azole agents with 1,3,4-oxadiazole side chains were designed and synthesized. The results of preliminary in vitro antifungal tests with eight human pathogenic compounds showed that all of the title compounds exhibited excellent activities against all of the tested fungi except Aspergillus fumigatus. Compounds 11e and 11f were found to be the most effective, with a minimum inhibitory concentration of 0.0039 μg/mL, followed by voriconazole, which has a MIC of 0.0625 μg/mL. The 1,3,4-oxadiazole side chain is not the major contributor but plays a role in eliciting the observed antifungal activity.
- Li, Liangjing,Ding, Hao,Wang, Baogang,Yu, Shichong,Zou, Yan,Chai, Xiaoyun,Wu, Qiuye
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supporting information
p. 192 - 194
(2014/01/17)
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- Methyl salicylate as a selective methylation agent for the esterification of carboxylic acids
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Methyl salicylate is a selective and inexpensive methylating agent for the esterification of carboxylic acids with a wide range of functional group tolerance. The intramolecular hydrogen bonds between the carboxylate and hydroxyl groups in methyl salicylate are essential for the transformation. Allyl, benzyl, methallyl, and propargyl salicylates can also be used as alkylating agents for the preparation of the corresponding alkyl carboxylates.
- Chen, Si,Jia, Lei,Li, Xiaonan,Luo, Meiming
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p. 263 - 268
(2014/03/21)
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- Copper-catalyzed decarboxylative methylation of aromatic carboxylic acids with PhI(OAc)2
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The copper-catalyzed decarboxylative methylation of aromatic carboxylic acids was developed by using PhI(OAc)2 to provide a new strategy for the methylation of aryl acids through the decarboxylation of alkyl acids. The mechanism and the roles of each reactant in the reaction were investigated extensively. Copyright
- Jiang, Yuyu,Pan, Shulei,Zhang, Yanghui,Yu, Jingxun,Liu, Hongqiang
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supporting information
p. 2027 - 2031
(2014/04/17)
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- An insight into the mechanism of the aerobic oxidation of aldehydes catalyzed by N-heterocyclic carbenes
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N-Heterocyclic carbene catalysis for the aerobic oxidation and esterification of aromatic aldehydes was monitored by ESI-MS (MS/MS) and the key intermediates were intercepted and characterized using the charge-tag strategy.
- Bortolini,Chiappe,Fogagnolo,Giovannini,Massi,Pomelli,Ragno
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supporting information
p. 2008 - 2011
(2014/03/21)
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- Copper-catalyzed methyl esterification of aromatic aldehydes and benzoic alcohols by TBHP as both oxidant and methyl source
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A copper-catalyzed synthesis of methyl esters from aromatic aldehydes in the presence of tert-butyl hydrogen peroxide (TBHP) was developed via a radical reaction mechanism. TBHP acts not only as an efficient oxidant, but also as a green methyl source in such transformation. Moreover, this method could also be efficiently extended to the methyl esterification of benzylic alcohols.
- Li, Pan,Zhao, Jingjing,Lang, Rui,Xia, Chungu,Li, Fuwei
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supporting information
p. 390 - 393
(2014/01/06)
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- Selective and efficient oxidation of benzylic alcohols to benzaldehydes and methyl benzoates by dibromo-5,5-dimethylhydantoin
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A selective and efficient method of oxidizing benzyl alcohols to benzaldehydes and methyl benzoates by using 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) as oxidant is developed. One-step conversion of benzyl alcohols to methyl benzoates in methanol at room temperature for 12 hours is achieved without any catalysts. Moreover, para-substituted benzyl alcohols are obtained in 86-98% yield. When dichloromethane is used as solvent, further oxidation of benzaldehydes to esters is well controlled, selectively affording benzaldehydes in 89-99% yield within 30 minutes.
- Li, Zhongzhou,Zhu, Wei,Bao, Jinlong,Zou, Xinzhuo
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supporting information
p. 1155 - 1164
(2014/04/03)
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- A general continuous flow method for palladium catalysed carbonylation reactions using single and multiple tube-in-tube gas-liquid microreactors
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A series of continuous flow chemistry processes that facilitate the palladium-catalysed carbonylation of aryl and vinyl iodides and aryl bromides with a range of alkoxy, hydroxy and amino nucleophiles is reported. Harnessing a semipermeable Teflon AF-2400 Tube-in-Tube assembly, these reactors permit the controlled transport of carbon monoxide into solution at elevated pressure to generate homogeneous flow streams, avoiding some potential issues associated with segmented flow gas-liquid reactors. As the volume of pressurised gas contained within the device is low, the hazards associated with this are potentially mitigated relative to comparable batch processes. We also show how the incorporation of a second in-line gas-flow reactor allows for the sequential introduction of two gases (carbon monoxide and a gaseous nucleophile) into the reaction stream. A Teflon AF-2400 Tube-in-Tube reactor facilitates the use of carbon monoxide in continuous-flow C-C bond forming reactions providing esters, amides, carboxylic acids, lactones and lactams. Two reactors can be used in series to permit the sequential addition of two reactive gases (CO and Me2NH) into the flow stream.
- Gross, Ulrike,Koos, Peter,O'brien, Matthew,Polyzos, Anastasios,Ley, Steven V.
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supporting information
p. 6418 - 6430
(2016/02/18)
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- Modified extra-large mesoporous silica supported Au-Ni as a highly efficient catalyst for oxidative coupling of aldehydes with methanol
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Herein, we report for the first time that a La-Mg composite oxide modified extra-large mesoporous FDU-12 supported Au-Ni bimetallic catalyst exhibits excellent performance for oxidative coupling of aldehydes (including benzyl and aliphatic aldehydes) with methanol to directly produce methyl esters.
- Han, Junxing,Zhang, Suojiang,Zhang, Juan,Yan, Ruiyi
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p. 58769 - 58772
(2015/02/19)
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- Synthesis, antibacterial activities, and 3d-qsar of sulfone derivatives containing 1, 3, 4-oxadiazole moiety
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A series of sulfone derivatives containing 1, 3, 4-oxadiazole moiety were prepared and evaluated for their antibacterial activities by the turbidimeter test. Most compounds inhibited growth of Ralstonia solanacearum (R. solanacearum) from tomato and tobacco bacterial wilt with high potency, among which compounds 5a and 5b exhibited the most potent inhibition against R. solanacearum from tomato and tobacco bacterial wilts with EC50 values of 19.77 and 8.29 μg/mL, respectively. Our results also demonstrated that 5a, 5b, and a number of other compounds were more potent than commercial bactericides Kocide 3000 and Thiodiazole Copper, which inhibited R. solanacearum from tomato bacterial wilt with EC50 values of 93.59 and 99.80 μg/mL and tobacco bacterial wilt with EC50 values of 45.91 and 216.70 μg/mL, respectively. The structure-activity relationship (SAR) of compounds was studied using three-dimensional quantitative structure-activity relationship (3D-QSAR) models created by comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) based on compound bioactivities against tomato and tobacco bacterial wilts. The 3D-QSAR models effectively predicted the correlation between inhibitory activity and steric-electrostatic properties of compounds.
- Li, Pei,Yin, Juan,Xu, Weiming,Wu, Jian,He, Ming,Hu, Deyu,Yang, Song,Song, Baoan
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p. 546 - 556
(2013/11/06)
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- Microwave assisted synthesis of biologically active 4-hydroxy-N′- (phenylcarbonyl)-2H-1,2-benzothiazine-3-carbohydrazide 1,1-dioxide derivatives
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Microwave assisted synthesis of a series of 4-hydroxy-N′- (phenylcarbonyl)-2H-1,2-benzothiazine-3-carbohydrazide 1,1-dioxides from sodium saccharin is reported. Sodium o-benzosulfimide was N-alkylated with ethyl chloroacetate followed by base catalyzed ring expansion to six membered 1,2-benzothiazine through Gabriel-Coleman type rearrangement yielding ethyl 4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide. It was later condensed with a series of benzohydrazides synthesized from various carboxylic acids to get the title compounds. All the synthesized compounds were subjected to preliminary evaluation for their biological activity against series of Gram positive, Gram negative bacteria and fungi. Some of the compounds showed marked activity against the selected microorganisms.
- Zaheer, Muhammad,Zia-Ur-Rehman, Muhammad,Rahman, Salma,Ahmed, Naveed,Chaudhary, Muhammad Nawaz
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p. 1492 - 1496
(2013/06/27)
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- Inhibition of tobacco bacterial wilt with sulfone derivatives containing an 1,3,4-oxadiazole moiety
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A series of new sulfone compounds containing the 1,3,4-oxadiazole moiety were designed and synthesized. Their structures were identified by 1H and 13C nuclear magnetic resonance and elemental analyses. Antibacterial bioassays indicated that most compounds exhibited promising in vitro antibacterial bioactivities against tobacco bacterial wilt at 200 μg/mL. The relationship between structure and antibacterial activity was also discussed. Among the title compounds, 5′c, 5′h, 5′i, and 5′j could inhibit mycelia growth of Ralstonia solanacearum in vitro by approximately 50% (EC50) at 39.8, 60.3, 47.9, and 32.1 μg/mL, respectively. Among them, compound 5′j was identified as the most promising candidate due to its stronger effect than that of Kocide 3000 [Cu(OH)2] within the same concentration range. Field trials demonstrated that the control effect of compound 5′j against tobacco bacterial wilt was better than that of the commercial bactericide Saisentong. For the first time, the present work demonstrated that sulfone derivatives containing 1,3,4-oxadiazole can be used to develop potential bactericides for plants.
- Xu, Wei-Ming,Han, Fei-Fei,He, Ming,Hu, De-Yu,He, Jiang,Yang, Song,Song, Bao-An
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scheme or table
p. 1036 - 1041
(2012/06/04)
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