- Remarkably Efficient Iridium Catalysts for Directed C(sp2)-H and C(sp3)-H Borylation of Diverse Classes of Substrates
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Here we describe the discovery of a new class of C-H borylation catalysts and their use for regioselective C-H borylation of aromatic, heteroaromatic, and aliphatic systems. The new catalysts have Ir-C(thienyl) or Ir-C(furyl) anionic ligands instead of the diamine-type neutral chelating ligands used in the standard C-H borylation conditions. It is reported that the employment of these newly discovered catalysts show excellent reactivity and ortho-selectivity for diverse classes of aromatic substrates with high isolated yields. Moreover, the catalysts proved to be efficient for a wide number of aliphatic substrates for selective C(sp3)-H bond borylations. Heterocyclic molecules are selectively borylated using the inherently elevated reactivity of the C-H bonds. A number of late-stage C-H functionalization have been described using the same catalysts. Furthermore, we show that one of the catalysts could be used even in open air for the C(sp2)-H and C(sp3)-H borylations enabling the method more general. Preliminary mechanistic studies suggest that the active catalytic intermediate is the Ir(bis)boryl complex, and the attached ligand acts as bidentate ligand. Collectively, this study underlines the discovery of new class of C-H borylation catalysts that should find wide application in the context of C-H functionalization chemistry.
- Chattopadhyay, Buddhadeb,Hassan, Mirja Md Mahamudul,Hoque, Md Emdadul
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supporting information
p. 5022 - 5037
(2021/05/04)
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- Ru-Catalyzed C(sp2)?H Bond Arylation of Benzamides Bearing a Novel 4-Aminoantipyrine as a Directing Group
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A novel design-based removable N,O-bidentate directing group based on cheap and commercially available 4-aminoantipyrine (AAP) is reported. Aromatic AP amides bearing 4-aminoantipyrine underwent efficient Ru-catalyzed C(sp2)?H arylation using [RuCl2(PPh3)3] as a catalyst and aryl bromides as electrophiles. The novel bidentate directing group enabled the C?H functionalization reaction with good scope, good functional group tolerance and in decent yields.
- Al Mamari, Hamad H.,Al Kiumi, Diana,Al Rashdi, Tamadher,Al Quraini, Huda,Al Rashdi, Malak,Al Sheraiqi, Sumayya,Al Harmali, Sara,Al Lamki, Mohammed,Al Sheidi, Ahmed,Al Zadjali, Asma
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supporting information
p. 3598 - 3603
(2021/07/22)
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- Hybrids of aurantiamide acetate and isopropylated genipin as potential anti-inflammatory agents: The design, synthesis, and biological evaluation
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A novel series of hybrids designed on the basis of aurantiamide acetate and isopropylated genipin were synthesized and biologically evaluated as anti-inflammatory agents. Among them, compound 7o exhibited the best inhibitory activity against TNF-α secretion (IC50?=?16.90?μM) and was selected for further in vitro and in vivo functional study. The results demonstrated that 7o was capable of suppressing the expression of LPS-induced iNOS and COX-2, as well as reducing the production of NO at the concentration of 5?μM, which may be resulted from its regulation of NF-κB signaling and MAPK signaling. Moreover, compound 7o exhibited favorable in vivo anti-inflammatory activity with an inhibition rate of 53.32% against xylene-induced ear swelling in mice at the dose of 5?mg/kg.
- Wang, Hongwei,Gao, Sufan,Li, Jiaming,Ma, Xiaodong,Liu, Wandong,Qian, Shihu
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p. 797 - 808
(2020/12/03)
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- 4-PHENYL-N-(PHENYL)THIAZOL-2-AMINE DERIVATIVES AND RELATED COMPOUNDS AS ARYL HYDROCARBON RECEPTOR (AHR) AGONISTS FOR THE TREATMENT OF E.G. ANGIOGENESIS IMPLICATED OR INFLAMMATORY DISORDERS
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4-phenyl-N-(phenyl)thiazol-2-amine and 4-(pyridin-3-yl)-N-( phenyl) thiazol-2-amine derivatives and the corresponding thiadiazole, thiophene, oxazole, oxadiazole, imidazole and triazole derivatives and related compounds as aryl hydrocarbon receptor (AHR) agonists for the treatment of angiogenesis implicated disorders, such as e.g. retinopathy, psoriasis, rheumatoid arthritis, obesity and cancer, or inflammatory disorders.
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Paragraph 00221; 00229
(2021/06/26)
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- NOVEL HETEROCYCLIC COMPOUND AND ORGANIC LIGHT EMITTING DEVICE COMPRISING THE SAME
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Provided is a heterocyclic compound Chemical Formula 1 or 2: and an organic light emitting device comprising the same.
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Paragraph 0094-0096
(2020/02/19)
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- Light-Switchable Antagonists for the Histamine H1 Receptor at the Isolated Guinea Pig Ileum
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The histamine H1 G protein-coupled receptor (GPCR) plays an important role in allergy and inflammation. Existing drugs that address the H1 receptor differ in their chemical structure, pharmacology, and side effects. Light-controllable spatial and temporal activity regulation of photochromic H1 ligands may contribute to a better mechanistic understanding and the development of improved correlations between ligand structure and pharmacologic effects. We report photochromic H1 receptor ligands, which were investigated in an organ-pharmacological assay. Initially, five photochromic azobenzene derivatives of reported dual H1–H4 receptor antagonists were designed, synthesized, photochemically characterized, and organ-pharmacologically tested on the isolated guinea pig ileum. Among them, one compound [trans-19: (Z)-1-(4-chlorophenyl)-1-(4-methylpiperazin-1-yl)-N-(4-((E)-phenyldiazenyl)phenyl)methanimine] retained the antagonistic activity of its non-photochromic lead, and trans–cis isomerization by irradiation induced a fourfold difference in the pharmacological response. Further structural optimization resulted in two bathochromically shifted derivatives of 19 [NO2-substituted 35 {(Z)-1-(4-chlorophenyl)-1-(4-methylpiperazin-1-yl)-N-(4-((E)-(4-nitrophenyl)diazenyl)phenyl)methanimine} and SO3?-substituted 41 {4-((E)-(4-(((Z)-(4-chlorophenyl)(4-methylpiperazin-1-yl)methylene)amino)phenyl)diazenyl)benzenesulfonate}], which do not require the use of UV light for photoisomerization and which also have improved solubility and show reduced tissue impairment. The trans isomers of both compounds showed a remarkable increase in antagonistic activity relative to their lead trans-19; furthermore, a 46-fold difference in activity on the isolated guinea pig ileum was observed between trans- and cis-35.
- Rustler, Karin,Pockes, Steffen,K?nig, Burkhard
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p. 636 - 644
(2019/02/14)
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- Visible light-induced transformation of aldehydes to esters, carboxylic anhydrides and amides
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A transition metal- and organophotocatalyst free synthesis of esters, carboxylic anhydrides and amides from aldehydes induced by visible-light has been reported. The proposed methodology can be carried out by the use of sunlight or artificial visible light as a blue LED source. The methodology has a very broad applicability and the desired products are obtained in very satisfactory yields.
- Gaspa, Silvia,Raposo, Inês,Pereira, Leonor,Mulas, Gabriele,Ricci, Pier Carlo,Porcheddu, Andrea,De Luca, Lidia
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supporting information
p. 10711 - 10715
(2019/07/15)
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- 4,5-Diaryl 3(2H)Furanones: Anti-inflammatory activity and influence on cancer growth
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Apart from their anti-inflammatory action, COX inhibitors have gathered the interest of many scientists due to their potential use for the treatment and prevention of cancer. It has been shown that cyclooxygenase inhibitors restrict cancer cell growth and are able to interact with known antitumor drugs, enhancing their in vitro and in vivo cytotoxicity. The permutation of hydrophilic and hydrophobic aryl groups in COX inhibitors leads to cardinal changes in the biological activity of the compounds. In the present study, thirteen heterocyclic coxib-like 4,5-diarylfuran-3(2H)-ones and their annelated derivatives-phenanthro[9,10-b]furan-3-ones-were synthesized and studied for anti-inflammatory and COX-1/2 inhibitory action and for their cytotoxic activity on the breast cancer (MCF-7) and squamous cell carcinoma (HSC-3) cell lines. The F-derivative of the -SOMe substituted furan-3(2H)-ones exhibited the best activity (COX-1 IC50 = 2.8 μM, anti-inflammatory activity (by carrageenan paw edema model) of 54% (dose 0.01 mmol/kg), and MCF-7 and HSC-3 cytotoxicity with IC50 values of 10 μM and 7.5 μM, respectively). A cytotoxic effect related to the COX-1 inhibitory action was observed and a synergistic effect with the anti-neoplastic drugs gefitinib and 5-fluorouracil was found. A phenanthrene derivative exhibited the best synergistic effect with gefitinib.
- Semenok, Dmitrii,Medvedev, Jury,Giassafaki, Lefki-P.,Lavdas, Iason,Vizirianakis, Ioannis S.,Eleftheriou, Phaedra,Gavalas, Antonis,Petrou, Anthi,Geronikaki, Athina
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-
- COMPOUND AND ORGANIC LIGHT EMITTING DEVICE COMPRISING THE SAME
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The specification of the formula 1 compound and organic light emitting number including [...] substrate. (by machine translation)
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-
Paragraph 0138; 0139; 0140; 0141
(2018/06/26)
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- An Efficient Synthesis of New 2-Aryl-5-phenylazenyl-1,3,4-oxadiazole Derivatives from N, N' -Diarylcarbonohydrazides
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A series of new 1,3,4-oxadiazoles conjugated to aromatic substituents by an azo linker was synthesized in a four-step reaction sequence, involving cyclodehydration of a N, N' -diacylhydrazine fragment and dehydrogenation of the neighboring hydrazine fragm
- Kedzia, Anna,Jasiak, Karolina,Kudelko, Agnieszka
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supporting information
p. 1745 - 1748
(2018/06/26)
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- Selective mono-alkylation of N-methoxybenzamides
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We report our latest discovery of norbornene derivative modulated highly mono-selective ortho-C-H activation alkylation reactions on arenes bearing simple mono-dentate coordinating groups. The reaction features the use of readily available benzamides and alkyl halides. During the study, we prepared 30 mono-alkylated aryl amides in good yields with good mono-selectivity. We have also demonstrated that structurally rigid alkenes such as norbornene and its derivatives are a good class of ligand and could be used for future direct C-H functionalizations. The utilization of norbornene type ligands for assistance in C-H activation processes has opened a new window for future molecular design using direct C-H functionalization strategies.
- Chen, Zenghua,Hu, Le'an,Zeng, Fanyun,Zhu, Ranran,Zheng, Shasha,Yu, Qingzhen,Huang, Jianhui
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supporting information
p. 4258 - 4261
(2017/04/21)
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- Palladium-catalysed cross-coupling as a key step in the synthesis of pyridyl-benzamides, -benzylamines and -sulfonamides
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Novel N-, O- and S-substituted pyridyl-benzamides, -benzylamines and -sulfonamides were prepared by means of palladium-catalysed cross-coupling reactions. The synthetic approach, using Pd2(dba)3as palladium source and rac-BINAP as supporting ligand, proved to be successful for C[sbnd]N, C[sbnd]O and C[sbnd]S cross-coupling reactions. One of the substrates underwent an unexpected nucleophilic aromatic substitution of fluorine, rather than the expected C[sbnd]N cross-coupling reaction.
- Changunda, Charles R.K.,Basson, Adriaan E.,van Vuuren, Sandy F.,Rousseau, Amanda L.,Bode, Moira L.
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p. 137 - 147
(2016/12/26)
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- Piperlongumine derived cyclic sulfonamides (sultams): Synthesis and in?vitro exploration for therapeutic potential against HeLa cancer cell lines
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A novel modification of piperlongumine is designed, bearing a cyclic sulphonamide (sultam) and its synthesis is described. For the first time herein we report the synthesis and biological evaluation of the natural product derived cyclic sulfonamides using Grubbs second generation catalyst (Grubbs II) via ring closing metathesis approach. Synthesis of a series of piperlongumine derived sultams is done in a moderate to good yield using Wittig reaction, Ring-Closing Metathesis (RCM) and, amide synthesis by using mixed anhydride, approach. All synthesized compounds were evaluated for anticancer activity and some demonstrated dose dependent reduction in HeLa cell growth. Of these 7, 10 and 14 significantly reduced the cell growth. Consequently their calculated GI50values were found to be 0.1 or 0.1?μM.
- Lad, Nitin P.,Kulkarni, Sarang,Sharma, Rajiv,Mascarenhas, Malcolm,Kulkarni, Mahesh R.,Pandit, Shivaji S.
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p. 870 - 878
(2016/12/18)
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- Metal-free oxidative self-coupling of aldehydes or alcohols to symmetric carboxylic anhydrides
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A metal-free synthesis of symmetrical anhydrides has been developed starting from aldehydes, both aliphatic and aromatic or primary benzylic alcohols. The reaction occurs at room temperature and makes use of trichloroisocyanuric acid (TCCA) as an oxidant providing the desired carboxylic anhydrides in satisfactory yields.
- Gaspa, Silvia,Porcheddu, Andrea,De Luca, Lidia
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supporting information
p. 2533 - 2536
(2017/06/13)
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- Anhydrides from aldehydes or alcohols via oxidative cross-coupling
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A novel type of metal-free oxidative cross-coupling for the synthesis of symmetrical and mixed anhydrides from aldehydes or benzylic alcohols has been developed. The aldehydes or alcohols were converted in situ into their corresponding acyl chlorides, which were then reacted with an array of carboxylic acids. The methodology has a general applicability, and was successfully employed to prepare either aromatic or aliphatic symmetrical anhydrides and mixed anhydrides, which are very unstable compounds.
- Gaspa, Silvia,Amura, Ida,Porcheddu, Andrea,De Luca, Lidia
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supporting information
p. 931 - 939
(2017/02/10)
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- From Lead to Drug Candidate: Optimization of 3-(Phenylethynyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine Derivatives as Agents for the Treatment of Triple Negative Breast Cancer
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Herein we report the sophisticated process of structural optimization toward a previously disclosed Src inhibitor, compound 1, which showed high potency in the treatment of triple negative breast cancer (TNBC) both in vitro and in vivo but had considerable toxicity. A series of 3-(phenylethynyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine derivatives were synthesized. In vitro cell-based phenotypic screening together with in vivo assays and structure-activity relationship (SAR) studies finally led to the discovery of N-(3-((4-amino-1-(trans-4-hydroxycyclohexyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)ethynyl)-4-methylphenyl)-4-methyl-3-(trifluoromethyl)benzamide (13an). 13an is a multikinase inhibitor, which potently inhibited Src (IC50 = 0.003 μM), KDR (IC50 = 0.032 μM), and several kinases involved in the MAPK signal transduction. This compound showed potent anti-TNBC activities both in vitro and in vivo, and good pharmacokinetic properties and low toxicity. Mechanisms of action of anti-TNBC were also investigated. Collectively, the data obtained in this study indicate that 13an could be a promising drug candidate for the treatment of TNBC and hence merits further studies.
- Zhang, Chun-Hui,Chen, Kai,Jiao, Yan,Li, Lin-Li,Li, Ya-Ping,Zhang, Rong-Jie,Zheng, Ming-Wu,Zhong, Lei,Huang, Shen-Zhen,Song, Chun-Li,Lin, Wan-Ting,Yang, Jiao,Xiang, Rong,Peng, Bing,Han, Jun-Hong,Lu, Guang-Wen,Wei, Yu-Quan,Yang, Sheng-Yong
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supporting information
p. 9788 - 9805
(2016/11/19)
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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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- Conformations, equilibrium thermodynamics and rotational barriers of secondary thiobenzanilides
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The article deals with conformational behaviour of 2-methoxy-2′-hydroxythiobenzanilides. The CS-NH group of these compounds preferentially adopts the Z-conformation. Entropy favours the Z-conformer over the E-conformer, whereas enthalpy slightly favours the E-conformer over the Z-conformer. The rotational barrier about the CS-NH bond was determined to be (81.5±0.4) kJ/mol. No significant rotational barrier was found on the Ar-CS and Ar-NH bonds. All experimental outcomes are compared with the results of quantum-chemical calculations.
- Kozic, Ján,Novák, Zdeněk,?ímal, Václav,Profant, Václav,Kune?, Ji?í,Vin?ová, Jarmila
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p. 2072 - 2083
(2016/04/09)
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- Transition-Metal-Free Synthesis of N-Aryl Hydroxamic Acids via Insertion of Arynes
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An efficient and transition-metal-free N-arylation of amides via the insertion of arynes into the N-H bonds in the N-alkoxy amides is described. A variety of the reactive functional groups including the reactive aldehyde carbonyl group, furan ring, carbon-carbon double bonds, and free N-H bond of indole are found to be compatible with this process. In particular, the protocol is applicable in the synthesis of structurally diverse N-aryl hydroxamates and hydroxamic acids derived from N-protecting amino acids and peptides. In the presence of multiple amide N-H bonds, the N-arylation reaction can proceed selectively in the N-H bonds of terminal N-OBn amides giving rise to the desired N-aryl hydroxamates.
- Zhang, Lanlan,Geng, Yu,Jin, Zhong
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p. 3542 - 3552
(2016/05/24)
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- Design, synthesis and fungicidal activity of N-substituted benzoyl-1,2,3,4-tetrahydroquinolyl-1-carboxamide
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To find a new lead compound with high biological activity, a series of N-substituted benzoyl-1,2,3,4-tetrahydroquinolyl-1-carboxamide were designed using linking active substructures method. The target compounds were synthesized from substituted benzoic acid by four steps and their structures were confirmed by 1H NMR, IR spectrum and elemental analysis. The in vitro bioassay results indicated that some target compounds exhibited excellent fungicidal activities, and the position of the substituents played an important role in fungicidal activities. Especially, compound 5n, exhibited better fungicidal activities than the commercial fungicide flutolanil against two tested fungi Valsa Mali and Sclerotinia sclerotiorum, with EC50 values of 3.44 and 2.63 mg/L, respectively. And it also displayed good in vivo fungicidal activity against S. sclerotiorum with the EC50 value of 29.52 mg/L.
- Lei, Peng,Xu, Yan,Du, Juan,Yang, Xin-Ling,Yuan, Hui-Zhu,Xu, Gao-Fei,Ling, Yun
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supporting information
p. 2544 - 2546
(2016/07/07)
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- Rh-Catalyzed annulations of: N -methoxybenzamides with ketenimines: Synthesis of 3-aminoisoindolinones and 3-diarylmethyleneisoindolinones with strong aggregation induced emission properties
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Rhodium-catalyzed C-H activation/annulation reactions of ketenimines with N-methoxybenzamides furnished 3-aminoisoindolin-1-ones and 3-(diarylmethylene)isoindolin-1-ones. The synthesized 3-(diarylmethylene)isoindolin-1-ones exhibited aggregation induced emissions in aqueous tetrahydrofuran solution and strong green-yellow emissions in solids.
- Zhou, Xiaorong,Peng, Zhixing,Zhao, Hongyang,Zhang, Zhiyin,Lu, Ping,Wang, Yanguang
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supporting information
p. 10676 - 10679
(2016/09/02)
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- Synthesis and biological activity of novel N-(3-furan-2-yl-1-phenyl-1H-pyrazol-5-yl) amides derivatives
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A series of novel N-(3-furan-2-yl-1-phenyl-1H-pyrazol-5-yl) amides derivatives were designed and synthesized. Their structures were confirmed by1H NMR,13C NMR and HRMS. All title compounds were evaluated for their herbicidal and antifungal activities. Preliminary bioassay results indicated that the title compounds showed good to moderate herbicidal activity at 1000?mg/L. Compound 6q presented the best activity against Digitaria sanguinalis (L) Scop., Amaranthus retroflexus L. and Arabidopsis thaliana with an inhibition degree of five. Compound 6d also showed an inhibition degree of five against D. sanguinalis. In addition, at 50?mg/L, most compounds exhibited good in vitro antifungal activity against Sclerotinia sclerotiorum, with compound 6c showing over 90% antifungal activity against S. sclerotiorum and Pellicularia sasakii.
- Huo, Jing-Qian,Ma, Liu-Yong,Zhang, Zhe,Fan, Zhi-Jin,Zhang, Jin-Lin,Beryozkina, Tetyana V,Bakulev, Vasiliy A
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p. 1547 - 1550
(2016/09/23)
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- Insights into the Pummerer synthesis of oxazolines
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A rapid and simple method to access unnatural 2-substituted 5-thio oxazolines has been developed. This methodology is based on a Pummerer reaction followed by an intramolecular nucleophilic substitution, which changes the paradigm for the normal use of a base in Pummerer chemistry. We also provide a useful two-step method for the synthesis of the starting material and a mechanistic proposal based on experimental observations, which contests the previously proposed reaction pathway. The reaction proved to be general, and different substituents, such as alkyl, aryl, alkenyl and functionalized groups, can be used without a significant decrease in efficiency.
- Becerra-Cely, Laura,Rueda-Espinosa, Juan,Ojeda-Porras, Andrea,Gamba-Sánchez, Diego
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p. 8474 - 8485
(2016/09/28)
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- Design and synthesis of N-benzoyl amino acid derivatives as DNA methylation inhibitors
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The inhibition of human DNA Methyl Transferases (DNMT) is a novel promising approach to address the epigenetic dysregulation of gene expression in different diseases. Inspired by the validated virtual screening hit NSC137546, a series of N-benzoyl amino acid analogues was synthesized and obtained compounds were assessed for their ability to inhibit DNMT-dependent DNA methylation in vitro. The biological screening allowed the definition of a set of preliminary structure–activity relationships and the identification of compounds promising for further development. Among the synthesized compounds, L-glutamic acid derivatives 22, 23, and 24 showed the highest ability to prevent DNA methylation in a total cell lysate. Compound 22 inhibited DNMT1 and DNMT3A activity in a concentration-dependent manner in the micromolar range. In addition, compound 22 proved to be stable in human serum and it was thus selected as a starting point for further biological studies.
- Garella, Davide,Atlante, Sandra,Borretto, Emily,Cocco, Mattia,Giorgis, Marta,Costale, Annalisa,Stevanato, Livio,Miglio, Gianluca,Cencioni, Chiara,Fernández-de Gortari, Eli,Medina-Franco, José L.,Spallotta, Francesco,Gaetano, Carlo,Bertinaria, Massimo
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p. 664 - 676
(2016/10/25)
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- Solution-phase microwave assisted parallel synthesis, biological evaluation and in silico docking studies of N,N′-disubstituted thioureas derived from 3-chlorobenzoic acid
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A facile and robust microwave-assisted solution phase parallel synthesis protocol was exercised for the development of a 38-member library of N,N′-disubstituted thiourea analogues (1–38) by using an identical set of conditions. The reaction time for synthesis of N,N′-disubstituted thiourea analogues was drastically reduced from a reported duration of 8–12 h for conventional methods to only 1.5–2.0 min. All the derivatives (1–38) were characterized by physico-analytical techniques such as elemental analysis in combination with FT-IR,1H,13C NMR and by single crystal XRD analysis have also been performed. These compounds were screened for their in vitro urease inhibition activities. Majority of compounds exhibited potent urease inhibition activities, however, the most significant activity was found for 16, with an IC50value of 1.23 ± 0.1 μM. Furthermore, the synthesized compounds were screened for their cytotoxic potential against lungs cancer cell lines. Cell culture studies demonstrated significant toxicity of the compounds on the cell lines, and the levels of toxicity were altered in the presence of various side groups. The molecular docking studies of the most potent inhibitors were performed to identify the probable binding modes in the active site of the urease enzymes. These compounds have a great potential and significance for further investigations.
- Rauf, Muhammad Khawar,Zaib, Sumera,Talib, Ammara,Ebihara, Masahiro,Badshah, Amin,Bolte, Michael,Iqbal, Jamshed
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p. 4452 - 4463
(2016/08/23)
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- Access to Atropisomerically En-riched Biaryls by the Coupling of Aryllithiums with Arynes under Control by Homochiral Oxazolines
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We report the preparation of axially stereoenriched biphenyls by the coupling of in situ generated aryllithiums and arynes using chiral oxazoline auxiliaries. The design of the aryne precursors, the choice of oxazoline and the reaction conditions were key to accessing the desired, highly substituted, atropisomerically enriched biarylic products. In one case, the two atropo-diastereomers could be obtained in isomerically pure form by column chromatographic separation and their absolute configurations established by X-ray crystallography. The stereoselectivity of the reaction seems to be governed by subtle parameters.
- Yalcouye, Boubacar,Berthelot-Bréhier, Ana?s,Augros, David,Panossian, Armen,Choppin, Sabine,Chessé, Matthieu,Colobert, Fran?oise,Leroux, Frédéric R.
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supporting information
p. 725 - 732
(2017/01/18)
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- Bis-arylalkenylalkyl acid compound, and preparation method and application thereof
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The invention relates to a bis-arylalkenylalkyl acid compound, and a preparation method and an application thereof. The structure of the compound is represented by the formula I. the definitions of *, R1, R2, R3, n1 and m are as in the specifications and the claims. The bis-arylalkenylalkyl acid compound provided by the invention has relatively high inhibition activity against sensitive strains and resistant strains, and can be used for preparing antibacterial drugs.
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-
Paragraph 0122; 0123; 0124; 0125; 0126; 0127; 0128
(2016/10/07)
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- Metal-Free Oxidative Cross Esterification of Alcohols via Acyl Chloride Formation
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A novel metal-free oxidative cross esterification of alcohols has been achieved using trichloroisocyanuric acid as an oxidant. The alcohols were converted in situ into their corresponding acyl chlorides, which were then reacted with primary and secondary aliphatic, benzylic and allylic alcohols and phenols. A wide variety of esters was obtained in satisfactory yields.
- Gaspa, Silvia,Porcheddu, Andrea,De Luca, Lidia
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supporting information
p. 154 - 158
(2016/01/25)
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- Rhodium(iii)-catalyzed C-H/C-C activation sequence: Vinylcyclopropanes as versatile synthons in direct C-H allylation reactions
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Succession of C-H activation and C-C activation was achieved by using a single rhodium(iii) catalyst. Vinylcyclopropanes were used as versatile coupling partners. Mechanistic studies suggest that the olefin insertion step is rate-determining and a facile β-carbon elimination is involved, which represents a novel ring opening mode of vinylcyclopropanes. This journal is
- Wu, Jia-Qiang,Qiu, Zhi-Ping,Zhang, Shang-Shi,Liu, Jing-Gong,Lao, Ye-Xing,Gu, Lian-Quan,Huang, Zhi-Shu,Li, Juan,Wang, Honggen
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supporting information
p. 77 - 80
(2015/01/09)
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- Ligand-promoted ortho-C-H amination with Pd catalysts
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2,4,6-Trimethoxypyridine is identified as an efficient ligand for promoting a Pd-catalyzed ortho-C-H amination of both benzamides and triflyl-protected benzylamines. This finding provides guidance for the development of ligands that can improve or enable PdII-catalyzed Csp2-H activation reactions directed by weakly coordinating functional groups.
- Zhu, Dajian,Yang, Guoqiang,He, Jian,Chu, Ling,Chen, Gang,Gong, Wei,Chen, Ke,Eastgate, Martin D.,Yu, Jin-Quan
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supporting information
p. 2497 - 2500
(2015/02/19)
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- Identification of anthranilamide derivatives as potential factor Xa inhibitors: Drug design, synthesis and biological evaluation
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The coagulation enzyme factor Xa (fXa) plays a crucial role in the blood coagulation cascade. In this study, three-dimensional fragment based drug design (FBDD) combined with structure-based pharmacophore (SBP) model and structural consensus docking were employed to identify novel fXa inhibitors. After a multi-stage virtual screening (VS) workflow, two hit compounds 3780 and 319 having persistent high performance were identified. Then, these two hit compounds and several analogs were synthesized and screened for in-vitro inhibition of fXa. The experimental data showed that most of the designed compounds displayed significant in vitro potency against fXa. Among them, compound 9b displayed the greatest in vitro potency against fXa with the IC50 value of 23 nM and excellent selectivity versus thrombin (IC50 Combining double low line 40 μM). Moreover, the prolongation of the prothrombin time (PT) was measured for compound 9b to evaluate its in vitro anticoagulant activity. As a result, compound 9b exhibited pronounced anticoagulant activity with the 2 × PT value of 8.7 μM.
- Xing, Junhao,Yang, Lingyun,Li, Hui,Li, Qing,Zhao, Leilei,Wang, Xinning,Zhang, Yuan,Zhou, Muxing,Zhou, Jinpei,Zhang, Huibin
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supporting information
p. 388 - 399
(2015/04/14)
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- Nickel-catalyzed directed sulfenylation of sp2 and sp3 C-H bonds
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Directed sulfenylation of both sp2 and sp3 C-H bonds was achieved through nickel catalyzed directed C-S bond formation, giving the desired product in good to excellent yield (up to 90%). Other metal cations, including Cu, Fe, Pd, Rh, Ru and Co, gave almost no reaction under identical conditions, which highlighted the unique reactivity of this Ni system.
- Ye, Xiaohan,Petersen, Jeffrey L.,Shi, Xiaodong
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supporting information
p. 7863 - 7866
(2015/05/13)
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- Carboxylate Assisted Ni-Catalyzed C-H Bond Allylation of Benzamides
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A one-step synthetic method was developed for allylation of benzamides using Ni(COD)2/RCO2H and [Ni(μ-H2O)(OOCCMe3)2(HOOCCMe3)2]2 (A′) catalytic system. Efficient, well-defined, air and moisture-stable Ni-pivalate complex was isolated and employed in catalytic allylation. The influence of solvent on product selectivity was also investigated. Nickel-back: A one-step synthetic method was developed for the allylation of benzamides using in situ formed nickel carboxylate Ni(COD)2/RCO2H catalyst (see scheme). The air and moisture stable Ni-pivalate complex was isolated and employed in catalytic allylation. The influence of solvent on product selectivity is discussed.
- Barsu, Nagaraju,Kalsi, Deepti,Sundararaju, Basker
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supporting information
p. 9364 - 9368
(2015/06/30)
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- Synthesis and biological evaluation of acetylenic chalcones as novel anti-inflammatory agents
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37 acetylenic chalcones were designed, synthesized by the Pd/Cu catalyzed Sonogashira coupling reaction, and evaluated for anti-inflammatory activities. A majority of these compounds showed remarkable inhibitions of the expression of inflammatory cytokine
- Zhao, Chengguang,Feng, Jianpeng,Zuo, Mingming,Zhang, Ying,Zhao, Jianfeng,Xu, Shanmei,Zheng, Suqing,Zhang, Yali,Tang, Qinqin,Lu, Zhongqiu,Liang, Guang,Zhou, Jianmin
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p. 567 - 572
(2015/08/18)
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- HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK
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Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.
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Paragraph 0146
(2014/05/24)
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- Design, synthesis, molecular docking studies and in vitro screening of ethyl 4-(3-benzoylthioureido) benzoates as urease inhibitors
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Thioureas are exceptionally versatile building blocks towards the synthesis of wide variety of heterocyclic systems, which also possess extensive range of pharmacological activities. The substituted benzoic acids were converted into corresponding acid chlorides, these acid chlorides were then treated with potassium thiocyanate in acetone and then the reaction mixture was refluxed for 1-2 h afford ethyl 4-(3-benzoylthioureido)benzoates thioureas in good yields. All the newly synthesized compounds were evaluated for their urease inhibitory activities and were found to be potent inhibitors of urease enzyme. Compounds 1f and 1g were identified as the most potent urease inhibitors (IC50 0.21 and 0.13 μM, respectively), and was 100-fold more potent than the standard inhibitors. Further molecular docking studies were carried out using the crystal structure of urease to find out the binding mode of the inhibitors with the enzyme.
- Saeed, Aamer,Khan, Muhammad Siraj,Rafique, Hummera,Shahid, Mohammad,Iqbal, Jamshed
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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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- Syntheses, third-order optical nonlinearity and DFT studies on benzoylferrocene derivatives
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A series of benzoylferrocene derivatives were synthesized and their third-order nonlinear optical (NLO) properties were evaluated in N,N-dimethyl-formamide at 800 nm using femtosecond degenerate four-wave mixing. The third-order NLO susceptibilities of synthesized compounds were 3.065-7.859 × 10-13 esu, with the response times in 49-70 fs. The second-order hyperpolarizabilities of the molecules of the compounds were 1.018-2.611 × 10-31 esu. The Density Functional Theory was used to calculate these benzoylferrocene derivatives. The theoretical study showed that the third-order NLO properties were increased with the increasing electron-withdrawing ability, which is accordance with the decreasing energy gap between the highest occupied and the lowest unoccupied molecular orbital. With the increasing of electron-withdrawing ability, the transferred charge to the substituent was increased and the affection on the electronic reallocate was increased. The experiment and theoretical results showed that the benzoylferrocene derivatives had potential nonlinear optical applications.
- Jia, Jianhong,Cui, Yanhong,Han, Liang,Sheng, Weijian,Li, Yujin,Gao, Jianrong
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p. 137 - 145
(2014/02/14)
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- Palladium(II)-catalyzed ortho-C-H arylation/alkylation of N-benzoyl α-amino ester derivatives
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The palladium-catalyzed arylation/alkylation of ortho-C-H bonds in N-benzoyl α-amino ester derivatives is described. In such a system both the NH-amido and the CO2R groups in the α-amino ester moieties play a role in successful C-H activation/C-C bond formation using iodoaryl coupling partners. A wide variety of functional groups and electron-rich/ deficient iodoarenes are tolerated. The yields obtained range from 20 to 95 %. C-H activation: The transformation of N-benzoyl amino acid ester derivatives (Gly, Asp) has been studied, in which the ortho-C-H activation/C-C bond formation was achieved by using the synergistic system Pd(OAc)2/AgOAc and halide compounds as coupling partners in t-Amyl-OH under air (see scheme).
- Misal Castro, Luis C.,Chatani, Naoto
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supporting information
p. 4548 - 4553
(2014/05/06)
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- Synthesis and antibacterial activity of novel levofloxacin analogues
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To search for new fluoroquinolones with better biological activities, twenty-six levofloxacin analogues were designed, synthesized and evaluated for antimicrobial activity against Gram-positive and Gram-negative bacterias. The results indicated that most compounds tested in this study exhibited comparable or better antimicrobial activity than levofloxacin as reference drug. Among these compounds, ZY6a was the most active compound against Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa, its activity was found to be 2 to 16 times better than levofloxacin.
- Zhang, Tong-Xin,Zhang, Wei-Xi,Zhu, Hua-Jun,Liang, Long,Cheng, Zhi-Peng,Luo, Mei-Ming
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p. 2344 - 2350
(2014/06/09)
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- Discovery of aroyl piperazine derivatives as IKr & I Ks dual inhibitors for cardiac arrhythmia treatment
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Combined blockade of IKr and IKs potassium channels is considered to be a promising therapeutic strategy for arrhythmia. In this study, we designed and synthesized 15 derivatives through modifying the hit compound 7 that was discovered by screening in-house database by whole-patch clamp technique. All of the compounds were evaluated on CHO and HEK 293 cell lines stably expressing hERG (IKr) and hKCNQ1/KCNE1 (IKs) potassium channels, and half of them exhibited improved dual IKr and IKs inhibitory effects compared to the hit compound. Compounds 7a and 7b with potent dual inhibitory activities were selected for further in vivo evaluations. Due to the preferable pharmacological behaviors, compound 7a deserved further optimization as a promising lead compound.
- Guo, Xiaoke,Sun, Haopeng,Du, Lvpei,Huang, Lu,Xu, Jing,Zhu, Yingying,Yu, Peng,Zhang, Xiaojin,Tang, Yiqun,You, Qidong
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p. 497 - 505
(2014/06/23)
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- Copper-mediated hydroxylation of arenes and heteroarenes directed by a removable bidentate auxiliary
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A copper-mediated C-H hydroxylation of arenes and heteroarenes using our newly developed PIP directing group has been developed. This procedure is scalable and compatible with a wide range of functional groups and heteroarenes, providing an operationally simple protocol for the synthesis of o-hydroxybenzamides. The hydroxylation of nicotinamides gave 4-oxo-1,4-dihydropyridine-3-carboxamides selectively. Preliminary mechanistic studies implicate that a basic ligand-enabled, irreversible, rate-determining CMD step is most likely involved in this process.
- Li, Xin,Liu, Yan-Hua,Gu, Wen-Jia,Li, Bo,Chen, Fa-Jie,Shi, Bing-Feng
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supporting information
p. 3904 - 3907
(2014/08/18)
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- Cu(II)-mediated ortho C-H alkynylation of (hetero)arenes with terminal alkynes
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Cu(II)-promoted ortho alkynylation of arenes and heteroarenes with terminal alkynes has been developed to prepare aryl alkynes. A variety of arenes and terminal alkynes bearing different substituents are compatible with this reaction, thus providing an alternative disconnection to Sonogashira coupling.
- Shang, Ming,Wang, Hong-Li,Sun, Shang-Zheng,Dai, Hui-Xiong,Yu, Jin-Quan
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supporting information
p. 11590 - 11593
(2014/10/15)
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- Direct allylation of aromatic and α,β-unsaturated carboxamides under ruthenium catalysis
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The ruthenium-catalyzed oxidative allylation of aromatic and α,β-unsaturated carboxamides with allylic carbonates is described. These transformations proceed readily with complete linear γ-selectivity of substituted allylic carbonates. the Partner Organisations 2014.
- Kim, Mirim,Sharma, Satyasheel,Mishra, Neeraj Kumar,Han, Sangil,Park, Jihye,Kim, Minyoung,Shin, Youngmi,Kwak, Jong Hwan,Han, Sang Hoon,Kim, In Su
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supporting information
p. 11303 - 11306
(2014/11/07)
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- Ni(II)-catalyzed oxidative coupling between C(sp2)-H in benzamides and C(sp3)-H in toluene derivatives
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Oxidative coupling between C(sp2)-H bonds and C(sp3)-H bonds is achieved by the Ni(II)-catalyzed reaction of benzamides containing an 8-aminoquinoline moiety as the directing group with toluene derivatives in the presence of heptafluoroisopropyl iodide as the oxidant. The method has a broad scope and shows high functional group compatibility. Toluene derivatives can be used as the coupling partner in an unreactive solvent.
- Aihara, Yoshinori,Tobisu, Mamoru,Fukumoto, Yoshiya,Chatani, Naoto
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supporting information
p. 15509 - 15512
(2014/12/11)
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- Mild rhodium(III)-catalyzed C-H allylation with 4-vinyl-1,3-dioxolan-2-ones: Direct and stereoselective synthesis of (E)-allylic alcohols
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A rhodium(III)-catalyzed C-H direct allylation reaction with 4-vinyl-1,3-dioxolan-2-ones has been developed. The reaction provides a facile and stereoselective access to substituted-(E)-allylic alcohols under mild and redox-neutral reaction conditions. Olefinic C-H activation is applicable, giving multifunctionalized skipped dienes in good yields. Minimal double-bond migration was observed.
- Zhang, Shang-Shi,Wu, Jia-Qiang,Lao, Ye-Xing,Liu, Xu-Ge,Liu, Yao,Lv, Wen-Xin,Tan, Dong-Hang,Zeng, Yao-Fu,Wang, Honggen
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supporting information
p. 6412 - 6415
(2015/01/09)
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- Copper-catalyzed phosphorylation of sp2 C-H bonds
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The phosphorylation of the ortho C-H bonds in benzamides containing an 8-aminoquinoline moiety as a bidentate directing group with H-phosphonates using copper as a catalyst under mild temperature conditions is described. This method shows high functional group compatibility and selectively gives mono-substituted products. This journal is
- Wang, Shan,Guo, Rui,Wang, Gao,Chen, Shan-Yong,Yu, Xiao-Qi
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supporting information
p. 12718 - 12721
(2015/05/20)
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- Cu(II)-mediated C-H amidation and amination of arenes: Exceptional compatibility with heterocycles
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A Cu(OAc)2-mediated C-H amidation and amination of arenes and heteroarenes has been developed using a readily removable directing group. A wide range of sulfonamides, amides, and anilines function as amine donors in this reaction. Heterocycles present in both reactants are tolerated, making this a broadly applicable method for the synthesis of a family of inhibitors including 2-benzamidobenzoic acids and N-phenylaminobenzoates.
- Shang, Ming,Sun, Shang-Zheng,Dai, Hui-Xiong,Yu, Jin-Quan
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supporting information
p. 3354 - 3357
(2014/03/21)
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- Nickel-catalyzed direct alkylation of C-H bonds in benzamides and acrylamides with functionalized alkyl halides via bidentate-chelation assistance
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The alkylation of the ortho C-H bonds in benzamides and acrylamides containing an 8-aminoquinoline moiety as a bidentate directing group with unactivated alkyl halides using nickel complexes as catalysts is described. The reaction shows high functional group compatibility. In reactions of meta-substituted aromatic amides, the reaction proceeds in a highly selective manner at the less hindered C-H bond.
- Aihara, Yoshinori,Chatani, Naoto
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supporting information
p. 5308 - 5311
(2013/05/21)
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- Synthesis and luminescence properties of 2-(benzylcarbamoyl)phenyl derivatives and their europium complexes
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Six novel 2-(benzylcarbamoyl)phenyl derivatives were synthesized and characterized by 1H-NMR, mass spectrometry, infrared spectra and elemental analysis. Their europium complexes were prepared and characterized by elemental analysis, EDTA titri
- Guo, Dongcai,He, Wei,Liu, Bang,Gou, Lining,Li, Ruixia
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p. 280 - 286
(2013/07/11)
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