- A Short, Atom-Economical Entry to Tetrahydroxanthenones
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A reaction that takes to water: The domino Michael addition/aldol condensation of salicylic aldehydes like 1 as the nucleophile and 2-cyclohexen-1-one (2) as the Michael acceptor provides 2,3,4,4a-tetrahydroxanthen-1-ones such as 3 in good yields. DABCO =
- Lesch, Bernhard,Braese, Stefan
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Read Online
- N-Type Doping of Organic Semiconductors: Immobilization via Covalent Anchoring
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Electrical doping is an important tool in the design of organic devices to modify charge carrier concentration in and Fermi level position of organic layers. The undesired diffusion of dopant molecules within common transport materials adversely affects b
- Reiser, Patrick,Benneckendorf, Frank S.,Barf, Marc-Michael,Müller, Lars,B?uerle, Rainer,Hillebrandt, Sabina,Beck, Sebastian,Lovrincic, Robert,Mankel, Eric,Freudenberg, Jan,J?nsch, Daniel,Kowalsky, Wolfgang,Pucci, Annemarie,Jaegermann, Wolfram,Bunz, Uwe H. F.,Müllen, Klaus
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Read Online
- Synthesis and antiviral activity of 1-hydroxy-2-(2-hydroxyphenyl)imidazoles against vaccinia virus
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2-(2-Hydroxyplienyl)imidazole derivatives were synthesized and tested for antiviral activity against vaccinia virus in Vero cell culture. 1-Methylimidazole 3-oxides, 1-methoxyimidazoles, and 1H-imidazoles showed no activity, whereas some 1-hydroxyimidazole derivatives hold promise, exhibiting antiviral activity and weak cytotoxicity.
- Nikitina,Bormotov,Shishkina,Tikhonov, A. Ya.,Perevalov
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Read Online
- Design and structural optimization of novel 2H-benzo[h]chromene derivatives that target AcrB and reverse bacterial multidrug resistance
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Drug efflux pumps have emerged as a new drug targets for the treatment of bacterial infections in view of its critical role in promoting multidrug resistance. Herein, novel chromanone and 2H-benzo[h]chromene derivatives were designed by means of integrated molecular design and structure-based pharmacophore modeling in an attempt to identify improved efflux pump inhibitors that target Escherichia coli AcrB. The compounds were tested for their efflux inhibitory activity, ability to inhibit efflux, and the effect on bacterial outer and inner membranes. Twenty-three novel structures were identified that synergized with antibacterials tested, inhibited Nile Red efflux, and acted specifically on the AcrB. Among them, WK2, WL7 and WL10 exhibiting broad-spectrum and high-efficiency efflux inhibitory activity were identified as potential ideal AcrB inhibitors. Molecular modeling further revealed that the strong π-π stacking interactions and hydrogen bond networks were the major contributors to tight binding of AcrB.
- Wang, Yinhu,Alenazy, Rawaf,Gu, Xinjie,Polyak, Steven W.,Zhang, Panpan,Sykes, Matthew J.,Zhang, Na,Venter, Henrietta,Ma, Shutao
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- Enantioselective Reduction of Ketones and Synthesis of 2-Methyl-2,3-dihydro-1-benzofuran Catalyzed by Chiral Spiroborate Ester
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Abstract: Asymmetric reduction of homobenzylic ketones was achieved through the use of chiral spiroborate ester catalyst. The catalyst is applicable for both analytical and industrial purposes since it is not sensitive to air and moisture. A rapid synthetic route has been developed for the preparation of (S)-2-methyl-2,3-dihydro-1-benzofuran via enantioselective reduction of homobenzylic ketone in the presence of a chiral spiroborate catalyst as the key step.
- Chopade, A. U.,Chopade, M. U.,Nikalje, M. D.,Patil, H. S.
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p. 611 - 618
(2021/06/02)
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- Improved Synthesis of MediPhos Ligands and Their Use in the Pd-Catalyzed Enantioselective N-Allylation of Glycine Esters
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A new class of chiral C2-symmetric diphosphines (MediPhos) was recently shown to give superior results in the Pd-catalyzed asymmetric N-allylation of amino acid esters. We here describe a new, improved protocol for the preparation of such ligands through bidirectional SN2-coupling of a tartrate-derived ditosylate with 6-alkyl-2-bromophenols followed by double lithiation/phosphanylation. This method gave access to a series of nine ligands with branched alkyl substituents, which were benchmarked in the enantioselective Pd-catalyzed N-allylation of tert-butyl glycinate with racemic (E)-2,8-dimethylnona-5-en-4-yl methyl carbonate (up to 95 % ee). In addition, the analogous transformation of tert-butyl glycinate with methyl (E)-nona-5-en-4-yl carbonate was optimized. The obtained allylic amines were then used in the stereoselective synthesis of the conformationally restricted proline-derived dipeptide analogs ProM-17 and ProM-21.
- Albat, Dominik,Neud?rfl, J?rg-Martin,Reiher, Martin,Schmalz, Hans-Günther
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supporting information
p. 4237 - 4242
(2021/08/24)
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- Tetrahydroquinazoline derivatives and pharmaceutical composition for preventing or treating psoriasis comprising the same
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The present invention relates to a tetrahydroquinazoline derivative and a pharmaceutical composition for preventing or treating psoriasis containing the same as an active ingredient. The compound provided in one aspect of the present invention has an effe
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Paragraph 0272-0276
(2020/11/06)
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- Catalyst-free photodecarbonylation ofortho-amino benzaldehyde
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It is almost a consensus that decarbonylation of the aldehyde group (-CHO) needs to not only be mediated by transition metal catalysts, but also requires severe reaction conditions (high temperature and long reaction time). In this work, inspired by the “conformational-selectivity-based” design strategy, we broke this consensus and discovered a catalyst-free photodecarbonylation of the aldehyde group. It revealed that decarbonylation can be easily achieved with visible light irradiation by introducing a tertiary amine into theortho-position of the aldehyde group. A diverse array of tertiary amines is tolerated by our photodecarbonylation under mild conditions. Furthermore, the (QM) computations of the mechanism and the experiments on well-designed special substrates revealed that our photodecarbonylation depends on the conformational specificity of the aldehyde group and tertiary amine, and occurs through an unusual [1,4]-H shift and a subsequent [1,3]-H shift.
- Li, Lamei,Wang, Songping,Wei, Wentao,Yan, Ming,Zhou, Jingwei
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supporting information
p. 3421 - 3426
(2020/06/25)
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- Design, synthesis and biological evaluation of dimethyl cardamonin (DMC) derivatives as P-glycoprotein-mediated multidrug resistance reversal agents
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Background: P-glycoprotein (P-gp) has been regarded as an important factor in the multidrug resistance (MDR) of tumor cells within the last decade, which can be solved by inhibiting P-gp to reverse MDR. Thus, it is an effective strategy to develop inhibitor of P-gp. Objective: In this study, the synthesis of a series of derivatives had been carried out by bioisosterism design on the basis of Dimethyl Cardamonin (DMC). Subsequently, we evaluated their reversal activities as potential P-glycoprotein (P-gp)-mediated Multidrug Resistance (MDR) agents. Methods: Dimethyl cardamonin derivatives were synthesized from acetophenones and the corresponding benzaldehydes in the presence of 40% KOH by Claisen-Schmidt reaction. Their cytotoxicity and reversal activities in vitro were assessed with MTT. Moreover, the compound B4 was evaluated by Doxorubicin (DOX) accumulation, Western blot and wound-healing assays deeply. Results and Discussion: The results showed that compounds B2, B4 and B6 had the potency of MDR reversers with little intrinsic cytotoxicity. Meanwhile, these compounds also demonstrated the capability to inhibit MCF-7 and MCF-7/DOX cells migration. Besides, the most compound B4 was selected for further study, which promoted the accumulation of DOX in MCF-7/DOX cells and inhibited the expressionof P-gp at protein levels. Conclusion: The above findings may provide new insights for the research and development of P-gp-mediated MDR reversal agents.
- Liu, Jianwen,Ma, Lei,Shi, Ximeng,Yin, Huanhuan,Zhao, Yuyu,Zhou, Licheng
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p. 1270 - 1282
(2020/10/06)
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- Potassium tert-Butoxide-Mediated Condensation Cascade Reaction: Transition Metal-Free Synthesis of Multisubstituted Aryl Indoles and Benzofurans
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An efficient and facile method to synthesize valuable disubstituted 2-aryl indoles and benzofurans in good yields has been demonstrated, based on a tert-butoxide-mediated condensation reaction involving a vinyl sulfoxide intermediate. Products are obtained from N- or O-benzyl benzaldehydes using dimethyl sulfoxide as a carbon source. The methodology features a wide functional group tolerance and transition metal-free environment. Preliminary mechanistic studies suggest that the reaction involves a tandem aldol reaction/Michael addition/dehydrosulfenylation/isomerization sequence through an ionic protocol.
- Yang, Pengfei,Xu, Weiyan,Wang, Rongchao,Zhang, Min,Xie, Chunsong,Zeng, Xiaofei,Wang, Min
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supporting information
p. 3658 - 3662
(2019/05/17)
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- Synthetic studies towards the penicisulfuranols: Synthesis of an advanced spirocyclic diketopiperazine intermediate
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The 2,5-diketopiperazine (DKP) moiety is a core feature of many natural products and medicinally relevant scaffolds. As part of our efforts directed towards a total synthesis of penicisulfuranol B, we have developed and report herein: (1) the preparation of an N-hydroxy diketopiperazine intermediate accessible via a molybdenum-mediated oxidation of a parent diketopiperazine, and (2) further synthetic studies leading to a novel spirocyclic dihydrobenzofuran-containing diketopiperazine.
- Gayler, Kevin M.,Lambert, Kyle M.,Wood, John L.
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supporting information
p. 3154 - 3159
(2019/01/29)
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- Phosphinous Acid Platinum Complex as Robust Catalyst for Oxidation: Comparison with Palladium and Mechanistic Investigations
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Secondary phosphine oxides proved to be effective preligands to stabilise a hydroxy-platinum based catalyst that allows the aerobic/anaerobic oxidation of challenging substrates. Kinetic comparisons showed that this system is more efficient and stable than previously reported similar palladium-based catalysts. A neutral platinum dimer bearing bridging hydroxy ligands has been isolated and fully characterised by X-ray diffraction and its involvement in the mechanism has been evidenced by mechanistic studies.
- Membrat, Romain,Vasseur, Alexandre,Martinez, Alexandre,Giordano, Laurent,Nuel, Didier
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supporting information
p. 5427 - 5434
(2018/10/20)
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- Benzo[h]chromene compounds, and application of same as AcrB efflux pump inhibitor to antibiosis
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The invention provides benzo[h]chromene compounds, and application of the same as an AcrB efflux pump inhibitor to antibiosis. The compounds have a structure as shown in a formula (I) which is described in the specification. The compounds have good antibiosis improving activity and efflux pump inhibiting activity.
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Paragraph 0121; 0122; 0123
(2018/11/27)
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- Preparation of acetals from aldehydes and alcohols under basic conditions
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A new, simple protocol for the synthesis of acetals under basic conditions from non-enolizable aldehydes and alcohols has been reported. Such reactivity is facilitated by a sodium alkoxide along with a corresponding trifluoroacetate ester, utilizing formation of sodium trifluoroacetate as a driving force for acetal formation. The usefulness of this protocol is demonstrated by its orthogonality with various acid-sensitive protecting groups and by good compatibility with functional groups, delivering synthetically useful acetals complementarily to the synthesis under acidic conditions from aldehydes and alcohols.
- Grabowski, Jakub,Granda, Jaros?aw M.,Jurczak, Janusz
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supporting information
p. 3114 - 3120
(2018/05/17)
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- Synthesis of five libraries of 6,5-fused heterocycles to establish the importance of the heterocyclic core for antiplasmodial activity
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Research has indicated that N-myristoyl transferase, an enzyme that catalyzes the addition of a myristate group to the N-terminal glycine residues of proteins, is involved in the myristoylation of more than 100 proteins. Genetic knockdown of the enzyme proved detrimental for the viability of the parasite P. knowlesi. A crystal structure of P. vivax N-myristoyl transferase (pvNMT), containing a 3-methyl benzofuran ligand has made it possible to assess key amino acid residue-ligand interactions. We synthesized five libraries of 6,5-fused heterocycles to establish the importance of the heterocycles as core scaffolds, as well as introduced various aromatic amides and esters to determine which carbonylic group affects the potency of each heterocyclic antiplasmodial agent.
- Jacobs, Leon,de Kock, Carmen,Taylor, Dale,Pelly, Stephen C.,Blackie, Margaret A.L.
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p. 5730 - 5741
(2018/11/06)
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- Novel leucine ureido derivatives as aminopeptidase N inhibitors using click chemistry
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The over-expression of aminopeptidase N on diverse malignant cells is associated with the tumor angiogenesis and metastasis. In this report, one new series of leucine ureido derivatives containing the triazole moiety was designed, synthesized and evaluated as APN inhibitors. Among them, compound 13v showed the best APN inhibition with an IC50 value of 0.089 ± 0.007 μM, which was two orders of magnitude lower than that of bestatin (IC50 = 9.4 ± 0.5 μM). Compound 13v also showed dose-dependent anti-angiogenesis activities. Even at the lower concentration (10 μM), compound 13v presented similar anti-angiogenesis activity compared with bestatin at 100 μM in both the human umbilical vein endothelial cells (HUVECs) capillary tube formation assay and the rat thoracic aorta rings test. Moreover, compared with bestatin, 13v exhibited comparable, if not better in vivo anti-metastasis activity in a mouse H22 pulmonary metastasis model.
- Cao, Jiangying,Ma, Chunhua,Zang, Jie,Gao, Shuai,Gao, Qianwen,Kong, Xiujie,Yan, Yugang,Liang, Xuewu,Ding, Qin'ge,Zhao, Chunlong,Wang, Binghe,Xu, Wenfang,Zhang, Yingjie
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p. 3145 - 3157
(2018/06/01)
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- Discovery and optimization of selective inhibitors of protein arginine methyltransferase 5 by docking-based virtual screening
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Protein arginine methyltransferase 5 (PRMT5) is a type II PRMT enzyme critical for diverse cellular processes and different types of cancers. Many efforts have been made to discover novel scaffold PRMT5 inhibitors. Herein, we report the discovery of DC-P33 as a hit compound of PRMT5 inhibitor, identified by molecular docking based virtual screening and 3H-labeled radioactive methylation assays. Structure-activity relationship (SAR) analysis was performed on the analogs of DC-P33 and then structural modifications were done to improve its activity. Among the derivatives, the compound DC-C01 displayed an IC50 value of 2.8 μM, and good selectivity toward PRMT1, EZH2 and DNMT3A. Moreover, DC-C01 exhibited anti-proliferation activities against Z-138, Maver-1, and Jeko-1 cancer cells with EC50 values of 12 μM, 12 μM, and 10.5 μM, respectively. Taken together, these results contribute to the development of specific inhibitors against PRMT5 and cancer therapy.
- Ye, Yan,Zhang, Bidong,Mao, Ruifeng,Zhang, Chenhua,Wang, Yulan,Xing, Jing,Liu, Yu-Chih,Luo, Xiaomin,Ding, Hong,Yang, Yaxi,Zhou, Bing,Jiang, Hualiang,Chen, Kaixian,Luo, Cheng,Zheng, Mingyue
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p. 3648 - 3661
(2017/07/11)
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- Natural α-methylenelactam analogues: Design, synthesis and evaluation of α-alkenyl-γ and δ-lactams as potential antifungal agents against Colletotrichum orbiculare
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In our continued efforts to improve the potential utility of the α-methylene-γ-lactone scaffold, 62 new and 59 known natural α-methylenelactam analogues including α-methylene-γ-lactams, α-arylidene-γ and δ-lactams, and 3-arylideneindolin-2-ones were synthesized as the bioisosteric analogues of the α-methylenelactone scaffold. The results of antifungal and cytotoxic activity indicated that among these derivatives compound (E)-1-(2, 6-dichlorobenzyl)-3-(2-fluorobenzylidene) pyrrolidin-2-one (Py51) possessed good selectivity with the highest antifungal activity against Colletotrichum orbiculare with IC50?=?10.4?μM but less cytotoxic activity with IC50?=?141.2?μM (against HepG2 cell line) and 161.2?μM (against human hepatic L02?cell line). Ultrastructural change studies performed by transmission electron microscope showed that Py51 could cause important cell morphological changes in C.?orbiculare, such as plasma membrane detached from cell wall, cell wall thickening, mitochondria disruption, a dramatic increase in vacuolation, and eventually a complete loss in the integrity of organelles. Significantly, mitochondria appeared one of the primary targets, as confirmed by their remarkably aberrant morphological changes. Analysis of structure–activity relationships revealed that incorporation of the aryl group into the α-exo-methylene and the N-benzyl substitution increased the activity. Meanwhile, the α-arylidene-γ-lactams have superiority in selectivity over the 3-arylideneindolin-2-ones. Based on the results, the N-benzyl substituted α-(2-fluorophenyl)-γ-lactam was identified as the most promising natural-based scaffold for further discovering and developing improved crop-protection agents.
- Delong, Wang,Lanying, Wang,Yongling, Wu,Shuang, Song,Juntao, Feng,Xing, Zhang
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p. 286 - 307
(2017/03/09)
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- Synthetic method of 1,3-substituted diphenylpropenes
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The present invention relates to a method for efficiently synthesizing a natural 1,3-substituted diphenylpropene compound having biological activity. The effective method synthesizes 1,3-substituted diphenylpropene compound 5 to 8 by using Friedel-Crafts
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Paragraph 0020; 0022
(2017/07/23)
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- Heterocyclic acene propanoic derivative as well as preparation method and application thereof
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The invention relates to a heterocyclic acene propanoic derivative as well as a preparation method and application thereof. A structural formula of the derivative is shown in the description. The heterocyclic acene propanoic derivative shows agonist activ
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Paragraph 0220; 0222; 0223; 0224
(2018/01/09)
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- Design and synthesis of neolamellarin a derivatives targeting heat shock protein 90
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In this study, we designed and synthesized a novel family of neolamellarin A derivatives that showed high inhibitory activity toward heat shock protein 90 (Hsp90), a kinase associated with cell proliferation. The 3,4-bis(catechol)pyrrole scaffold and the benzyl group with methoxy modification at N position of pyrrole are essential to the Hsp90 inhibitory activity and cytotoxicity of these compounds. Western blot analysis demonstrated that these compounds induced dramatic depletion of the examined client proteins of Hsp90, and accelerated cancer cell apoptosis. Docking simulations suggested that the binding mode of 9p was similar to that of the VER49009, a potent inhibitor of Hsp90. Further molecular dynamics simulation indicated that the hydrophobic interactions as well as the hydrogen bonds contributed to the high affinity of 9p to Hsp90.
- Jiang, Long,Yin, Ruijuan,Wang, Xueting,Dai, Jiajia,Li, Jing,Jiang, Tao,Yu, Rilei
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supporting information
p. 24 - 33
(2017/04/21)
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- A convenient approach to an advanced intermediate toward the naturally occurring, bioactive 6-substituted 5-hydroxy-4-aryl-1H-quinolin-2-ones
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5-Hydroxy-4-aryl-3,4-dihydro-1H-quinolin-2-ones are a small family of natural products isolated from fungal strains of Penicillium and Aspergillus. Most of its members, which are insecticides and anthelmintics, carry an isoprenoid C-6 side chain. The synthesis of a 6-propenyl-substituted advanced intermediate for the total synthesis of these natural products is presented in this paper. This was achieved through the stereoselective construction of a β,β-diarylacrylate derivative from 6-nitrosalicylaldehyde, using a Wittig olefination and a Heck-Matsuda arylation, followed by a selective Fe0-mediated reductive cyclization. Installation of the 6-propenyl side chain was performed by 5-O-allylation of the heterocycle, followed by Claisen rearrangement and conjugative migration of the allyl double bond, as the key steps. The Grubbs II-catalyzed olefin cross metathesis of the 6-allyl moiety with 2-methylbut-2-ene to afford a precursor of peniprequinolone is also reported.
- Simonetti, Sebastián O.,Larghi, Enrique L.,Kaufman, Teodoro S.
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supporting information
p. 2625 - 2636
(2016/03/05)
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- Novel Total Synthesis of Mansouramycin B
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A novel total synthesis of Mansouramycin B (1) was performed via 10 steps in 28% overall yield starting from the readily available and cheap salicylaldehyde. Two key steps of this total synthesis are noteworthy. The first one is base-promoted one-pot aerobic aromatization of N-tosyltetrahydroisoquinoline 6, the second one is oxidation of 5-hydroxy-3-methyl-isoquinoline 8 with iodobenzene diacetate [PhI(OAc)2].
- Zhang, Yi,Shi, Xiaoxin,Meng, Tianzhuo,Fan, Qiqi,Lu, Xia
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p. 683 - 688
(2016/07/22)
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- Solvent responsive catalyst improves NMR sensitivity: Via efficient magnetisation transfer
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A bidentate iridium carbene complex, Ir(κC,O-L1)(COD), has been synthesised which contains a strongly electron donating carbene ligand that is functionalised by a cis-spanning phenolate group. This complex acts as a precursor to effective magne
- Ruddlesden, Amy J.,Duckett, Simon B.
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supporting information
p. 8467 - 8470
(2016/07/07)
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- Synthesis of 2,3-Disubstituted Indoles and Benzofurans by the Tandem Reaction of Rhodium(II)-Catalyzed Intramolecular C-H Insertion and Oxygen-Mediated Oxidation
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A highly effective and straightforward method to construct a wide range of functionalized 2,3-disubstituted indoles has been developed. The method involves the tandem reaction of rhodium(II)-catalyzed denitrogenative annulation of triazole-based benzyl an
- Shen, Hongjuan,Fu, Junkai,Yuan, Hao,Gong, Jianxian,Yang, Zhen
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p. 10180 - 10192
(2016/11/17)
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- Cobalt-Catalyzed Annulation of Salicylaldehydes and Alkynes to Form Chromones and 4-Chromanones
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A unique cobalt(I)-diphosphine catalytic system has been identified for the coupling of salicylaldehyde (SA) and an internal alkyne affording a dehydrogenative annulation product (chromone) or a reductive annulation product (4-chromanone) depending on the alkyne substituents. Distinct from related rhodium(I)- and rhodium(III)-catalyzed reactions of SA and alkynes, these annulation reactions feature aldehyde C-H oxidative addition of SA and subsequent hydrometalation of the C=O bond of another SA molecule as common key steps. The reductive annulation to 4-chromanones also involves the action of Zn as a stoichiometric reductant. In addition to these mechanistic features, the CoI catalysis described herein is complementary to the RhI- and RhIII-catalyzed reactions of SA and internal alkynes, particularly in the context of chromone synthesis.
- Yang, Junfeng,Yoshikai, Naohiko
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supporting information
p. 2870 - 2874
(2016/02/27)
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- Highly Active Multidentate Ligand-Based Alkyne Metathesis Catalysts
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Alkyne metathesis catalysts composed of molybdenum(VI) propylidyne and multidentate tris(2-hydroxylbenzyl)methane ligands have been developed, which exhibit excellent stability (remains active in solution for months at room temperature), high activity, an
- Du, Ya,Yang, Haishen,Zhu, Chengpu,Ortiz, Michael,Okochi, Kenji D.,Shoemaker, Richard,Jin, Yinghua,Zhang, Wei
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supporting information
p. 7959 - 7963
(2016/06/09)
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- Syntheses and anti-inflammatory activity of natural 1,3-diarylpropenes
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First syntheses of five natural 1,3-diarylpropenes (cinnamylphenols) 2-4, 7, and 8 along with synthesis of two other natural 1,3-diarylpropenes 1 and 5 and E-isomer of mucronulastyrene (6) were achieved by Friedel- Crafts alkylation as a key step. Subsequ
- Jung, Jong-Woon,Kim, Jin-Kyung,Jun, Jong-Gab
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p. 632 - 637
(2016/06/09)
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- Synthesis and study of prototropic tautomerism of 2-(2-hydroxyphenyl)-1-hydroxyimidazoles
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Novel 2-(2-hydroxyphenyl) substituted imidazoles have been synthesized. A prototropic tautomerism of the 1-hydroxyimidazole derivatives has been studied. X-ray diffraction analysis and IR-spectroscopy have revealed that in the solid state the title compounds exist as the N-hydroxy tautomers. The 1H and 13C NMR spectra of the new imidazole derivatives are discussed. It has been shown that in chloroform solutions 5-carbonyl substituted 2-(2-hydroxyphenyl)-1-hydroxyimidazoles exist in the N-hydroxy tautomeric form. A transition to DMSO results in the existence of the 1-hydroxyimidazoles under study as the N-oxide tautomers.
- Nikitina, Polina A.,Peregudov, Aleksandr S.,Koldaeva, Tatiana Yu.,Kuz'Mina, Ludmila G.,Adiulin, Evgeniy I.,Tkach, Iosif I.,Perevalov, Valery P.
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p. 5217 - 5228
(2015/07/15)
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- Synthesis of 5-arylisoxazole-3-carboxylates derived from salicylaldehyde
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A procedure has been developed for the synthesis of 5-arylisoxazole-3-carboxylates on the basis of phenols and oximes derived from salicylaldehyde. Selective reduction of 4-(2-ethoxybenzylideneaminophenyl) 5-arylisoxazole-3-carboxylates afforded the corresponding amines.
- Petkevich, S. K.,Dikusar, E. A.,Potkin, V. I.,Mikhei, I. V.
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- Pd(OAc)2/S=PPh3 accelerated activation of gem-dichloroalkenes for the construction of 3-arylchromones
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The Pd-catalyzed regioselective intramolecular nucleophilic substitution of gem-dichloroalkene derivatives with salicylaldehydes leading to the synthesis of 3-arylchromones has been developed. Pd(OAc)2/S=PPh3 could activate gem-dichloroalkenes and undergo nucleophilic substitution by salicylaldehydes with the aid of a base.
- Liu, Jianming,Song, Weiwei,Yue, Yuanyuan,Liu, Ren,Yi, Hong,Zhuo, Kelei,Lei, Aiwen
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supporting information
p. 17576 - 17579
(2015/12/08)
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- Synthesis and Biological Evaluation of Nitrated 7-, 8-, 9-, and 10-Hydroxyindenoisoquinolines as Potential Dual Topoisomerase i (Top1)-Tyrosyl-DNA Phosphodiesterase i (TDP1) Inhibitors
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The structure-activity relationships and hit-to-lead optimization of dual Top1-TDP1 inhibitors in the indenoisoquinoline drug class were investigated. A series of nitrated 7-, 8-, 9-, and 10-hydroxyindenoisoquinolines were synthesized and evaluated. Several compounds displayed potent dual Top1-TDP1 inhibition. The 9-hydroxy series exhibited potencies and cytotoxicities vs Top1 that surpassed those of camptothecin (CPT), the natural alkaloid that is being used as a standard in the Top1-mediated DNA cleavage assay. One member of this series was a more potent Top1 inhibitor at a concentration of 5 nM and produced a more stable ternary drug-DNA-Top1 cleavage complex than CPT. (Chemical Equation Presented).
- Nguyen, Trung Xuan,Abdelmalak, Monica,Marchand, Christophe,Agama, Keli,Pommier, Yves,Cushman, Mark
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p. 3188 - 3208
(2015/04/27)
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- SULFAMATE DERIVATIVE COMPOUNDS FOR USE IN TREATING OR ALLEVIATING PAIN
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The present invention relates to sulfamate derivative compounds and a composition for treating and/or alleviating pain containing the sulfamate derivative compounds or a pharmaceutically acceptable salt thereof as an active ingredient. More specifically,
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Page/Page column 23-24
(2015/06/25)
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- The flavan-isoflavan rearrangement: Bioinspired synthetic access to isoflavonoids via 1,2-shift-alkylation sequence
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An approach to 2-substituted isoflavonoids is reported based on the 1,2-shift of the aryl group in the catechin skeleton followed by the in situ alkylation. Synthesis of (-)-equol, a natural isoflavan with estrogenic activities, was achieved.
- Nakamura, Kayo,Ohmori, Ken,Suzuki, Keisuke
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supporting information
p. 7012 - 7014
(2015/04/22)
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- HUMAN PLASMA KALLIKREIN INHIBITORS
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Disclosed are compounds of formula (I), as described herein, and pharmaceutically acceptable salts thereof. The compounds are inhibitors of plasma kallikrein. Also provided are pharmaceutical compositions comprising at least one compound of the invention, and methods involving use of the compounds and compositions of the invention in the treatment and prevention of diseases and conditions characterized by unwanted plasma kallikrein activity.
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Page/Page column 252; 253
(2015/11/02)
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- Synthesis and evaluation of 3-hydroxy-3-phenylpropanoate ester-AZT conjugates as potential dual-action HIV-1 Integrase and Reverse Transcriptase inhibitors
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Novel 3-hydroxy-3-phenylpropanoate ester-azidothymidine (AZT) conjugates have been prepared using Baylis-Hillman methodology, and their potential as dual-action HIV-1 Integrase and Reverse Transcriptase inhibitors has been explored using enzyme inhibition
- Manyeruke, Meloddy H.,Olomola, Temitope O.,Majumder, Swarup,Abrahams, Shaakira,Isaacs, Michelle,Mautsa, Nicodemus,Mosebi, Salerwe,Mnkandhla, Dumisani,Hewer, Raymond,Hoppe, Heinrich C.,Klein, Rosalyn,Kaye, Perry T.
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p. 7521 - 7528
(2015/12/18)
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- Coumarin moiety can enhance abilities of chalcones to inhibit DNA oxidation and to scavenge radicals
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Coumarin and chalcone are naturally occurring compounds, and coumarin as a functional group was combined with chalcone in this work, aiming to test the inhibitory effects of coumarin-substituted chalcones on the oxidation of DNA and on scavenging radicals. It was found that the antioxidant activity of hydroxyl group attaching to coumarin can be increased by hydroxyl groups attaching to chalcone. The double hydroxyl groups at adjacent position exhibited high abilities to inhibit Cu2+/glutathione-induced oxidation of DNA and to trap 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS+) as well as 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH). Especially, the double hydroxyl groups in chalcone were able to protect DNA against 2,2′-azobis(2-amidinopropanehydrochloride) (AAPH)-induced oxidation significantly. On the other hand, the hydroxyl group attaching to coumarin exhibited high ability to inhibit OH-induced oxidation of DNA. Therefore, coumarin-appended chalcones exhibited higher antioxidant effectiveness with only single or double phenolic hydroxyl groups contained.
- Xi, Gao-Lei,Liu, Zai-Qun
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p. 8397 - 8404
(2015/03/04)
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- A novel series of 6-substituted 3-(pyrrolidin-1-ylmethyl)chromen-2-ones as selective monoamine oxidase (MAO) A inhibitors
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A series of 6-substituted 3-(pyrrolidin-1-ylmethyl)chromen-2-ones (coumarins) have been synthesized and their inhibitory activity to human monoamine oxidase A (MAO A) and B (MAO B) determined. Incorporation of a basic amino function in the C3 position together with substitution at the C6 position produced novel coumarin compounds with selectivity for the MAO A subtype. Substitution in the C6 position with small hydrophilic groups such as hydroxy (19, IC50 = 1.46 μM) or amino (18, IC50 = 3.77 μM) gave the most potent and selective compounds for MAO A. These compounds also showed excellent aqueous solubility properties. Compound 18 [6-amino-3- (pyrrolidin-1-ylmethyl)chromen-2-one] administrated in vivo induced in rat brain a neurotransmitter metabolite profile typical of MAO A inhibition: decreased 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) but increased 3-methoxytyramine (3-MT) levels.
- Mattsson, Cecilia,Svensson, Peder,Sonesson, Clas
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p. 177 - 186
(2014/01/23)
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- Evaluation of Baylis-Hillman Routes to 3-(Aminomethyl)coumarin Derivatives
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The relative merits of two different Baylis-Hillman approaches toward the preparation of coumarin derivatives, containing peptide-like side chains, have been explored. In one approach, use of methyl acrylate as the activated alkene requires a protecting group strategy, an approach that is not necessary when using tert-butyl acrylate. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications for the following free supplemental resource(s): Full experimental and spectral details.]
- Olasupo, Idris,Rose, Nathan R.,Klein, Rosalyn,Adams, Luqman A.,Familoni, Oluwole B.,Kaye, Perry T.
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p. 251 - 258
(2013/12/04)
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- Synthesis of cinnamate ester-AZT conjugates as potential dual-action HIV-1 integrase and reverse transcriptase inhibitors
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Synthetic approaches to a series of novel cinnamate ester-AZT conjugates have been explored and a successful pathway has finally been developed. α-(Halomethyl)cinnamate esters, obtained in high yield by treating benzyl-protected salicylaldehde-derived Bay
- Olomola, Temitope O.,Klein, Rosalyn,Kaye, Perry T.
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p. 9449 - 9455
(2015/03/03)
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- Diaryl-1,2,4-oxadiazole antioxidants: Synthesis and properties of inhibiting the oxidation of DNA and scavenging radicals
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Six 1,2,4-oxadiazole derivatives were prepared in order to compare their abilities to protect DNA against radical-mediated oxidation and to scavenge radicals. These derivatives had a structure based on disubstituted 1,2,4-oxadiazole, in which a vanillin group (A ring) and a substituted benzene group (B ring) were the substituents. The functional group at B ring was assigned as ortho- or meta-hydroxylbenzene group, ortho-chlorobenzene group, no group contained, and pyridine group or vanillin group at B ring. It was found that the compound with two vanillin groups attaching to oxadiazole can trap 2.05 radicals in protecting DNA against 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH)-induced oxidation, and the compound with an ortho-hydroxylbenzene group at B ring can trap 1.78 radicals. The compound with an ortho-chlorobenzene group at B ring exhibited the highest ability to inhibit ·OH-induced oxidation of DNA, while the compound with a meta-hydroxylbenzene group at B ring inhibited Cu2+/glutathione (GSH)-induced oxidation of DNA efficiently. The ortho- and para-hydroxylbenzene groups at B ring made the compounds possess the highest rate constant (k) in scavenging 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS+.) and 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH). Therefore, only a few hydroxyl groups can markedly enhance the activity of the core-branched antioxidant, which may be a novel structural feature in designing antioxidant.
- Zhao, Chao,Liu, Zai-Qun
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p. 842 - 849
(2013/04/24)
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- Antioxidant effectiveness generated by one or two phenolic hydroxyl groups in coumarin-substituted dihydropyrazoles
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A cascade operation was designed to synthesize nine coumarin-substituted dihydropyrazoles with only one or two phenolic hydroxyl groups contained. Antioxidant abilities of the obtained compounds were evaluated by inhibiting 2,2′-azobis(2-amidinopropanehydrochloride) (AAPH)-, Cu2+/ glutathione (GSH)-, and .OH-induced oxidation of DNA. It was found that less phenolic hydroxyl groups can enhance the abilities of coumarin-substituted dihydropyrazoles to protect DNA against the oxidation. Moreover, these coumarin-substituted dihydropyrazoles were employed to scavenge 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS+.), 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH), and galvinoxyl radical, respectively. It was found that double phenolic hydroxyl groups were more beneficial for enhancing the abilities of coumarin-substituted dihydropyrazoles to quench the aforementioned radicals. Therefore, dihydropyrazole linked with coumarin exhibited powerful antioxidant effectiveness even in the case of less phenolic hydroxyl groups involved.
- Xi, Gao-Lei,Liu, Zai-Qun
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p. 385 - 393
(2013/10/01)
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- The homo-PADAM protocol: Stereoselective and operationally simple synthesis of α-oxo- or α-hydroxy-γ-acylaminoamides and chromanes
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A straightforward and fully stereoselective synthesis of a new class of peptidomimetics, that is α-oxo-γ-acylaminoamides, was achieved starting from various benzaldehydes by a sequence of 1) an asymmetric organocatalytic Mannich reaction, 2) a Passerini multicomponent reaction, 3) an amine deprotection-acyl migration protocol, and 4) a final oxidation. The whole sequence can be performed without purification of the intermediates and represents the first example of a homo-Passerini-amine deprotection-acyl migration (PADAM) strategy. Highly stereoselective reduction of the α-oxo-γ-acylaminoamides afforded α-hydroxy-γ- acylaminoamides as well. In some cases both diastereomers were obtained by simply changing the reducing agent. Finally, starting from protected salicylaldehyde, the same sequence, followed by a Mitsunobu cyclization, afforded highly substituted chromanes. Copyright
- Morana, Fabio,Basso, Andrea,Riva, Renata,Rocca, Valeria,Banfi, Luca
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supporting information
p. 4563 - 4569
(2013/04/24)
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- Synthesis and cytotoxic activities of novel hybrid 2-phenyl-3- alkylbenzofuran and imidazole/triazole compounds
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A series of novel hybrid compounds of 2-phenyl-3-alkylbenzofuran and imidazole or triazole were prepared and evaluated in vitro against a panel of human tumor cell lines. The results suggest that the 2-ethyl-imidazole ring, and substitution of the imidazo
- Chen, Wen,Deng, Xiao-Yan,Li, Yan,Yang, Li-Juan,Wan, Wei-Chao,Wang, Xue-Quan,Zhang, Hong-Bin,Yang, Xiao-Dong
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supporting information
p. 4297 - 4302
(2013/07/26)
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- Practical asymmetric catalytic synthesis of spiroketals and chiral diphosphine ligands
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A practical procedure has been developed for efficient synthesis of chiral aromatic spiroketals and the relevant diphosphine ligands. The procedure includes first asymmetric hydrogenation of readily available α, α'-bis(2-benzyloxyarylidene) ketones cat-al
- Wang, Xiaoming,Wang, Xubin,Guo, Peihua,Wang, Zheng,Ding, Kuiling
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supporting information
p. 2900 - 2907
(2014/03/21)
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- Highly Active Multidentate Catalysts for Efficient Alkyne Metathesis
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The invention relates to highly active and selective catalysts for alkyne metathesis. In one aspect, the invention includes a multidentate organic ligand wherein one substrate-binding site of the metal center is blocked. In another aspect, the invention includes N-quaternized or silane-based multidentate organic ligands, capable of binding to metals. In yet another aspect, the invention includes N-quaternized or silane-based multidentate catalysts. The catalysts of the invention show high robustness, strong resistance to small alkyne polymerization and significantly enhanced catalytic activity compared to their corresponding non-quaternized or non-silane-based multidentate catalyst analogues.
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Paragraph 0174
(2013/10/08)
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- The synthesis and SAR study of phenylalanine-derived (Z)-5-arylmethylidene rhodanines as anti-methicillin-resistant Staphylococcus aureus (MRSA) compounds
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A focused library of rhodanine compounds containing novel substituents at the C5-position was synthesized and tested in vitro against a panel of clinically relevant MRSA strains. The present SAR study was based on our lead compound 1 (MIC = 1.95 μg/mL), with a focus on identifying optimal C5-arylidene substituents. In order to obtain this objective, we condensed several unique aromatic aldehydes with phenylalanine-derived rhodanine intermediates to obtain C5-substituted target rhodanine compounds for evaluation as anti-MRSA compounds. These efforts produced three compounds with significant efficacy: 23, 32 and 44, with MIC values ranging from 0.98 to 1.95 μg/mL against all tested MRSA strains as compared to the reference antibiotics penicillin G (MIC = 15.60-250.0 μg/mL) and ciprofloxacin (MIC = 7.80-62.50 μg/mL) and comparable to that of vancomycin (MIC = 0.48 μg/mL). In addition, compounds 24, 28, 37, 41, 46 and 48 (MIC = 1.95-3.90 μg/mL) were efficacious against all MRSA strains. The majority of the synthesized compounds had bactericidal activity at concentrations only two to fourfold higher than their MIC. Overall, the results suggest that compounds 23, 32 and 44 may be of potential use in the treatment of MRSA infections.
- Patel, Bhargav A.,Ashby Jr., Charles R.,Hardej, Diane,Talele, Tanaji T.
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supporting information
p. 5523 - 5527
(2013/10/01)
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- Amino acids derived benzoxazepines: Design, synthesis and antitumor activity
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Two series of new benzoxazepines substituted with different alkyl amino ethyl chains were synthesized comprising synthetic steps of inter and intramolecular Mitsunobu reaction, lithium aluminium hydride (LAH) reduction, debenzylation, bimolecular nucleophilic substitution (SN2) reaction. The present study investigates the effect of a tyrosine-based benzoxazepine derivative in human breast cancer cells MCF-7 and MDA-MB-231 and in breast cancer animal model. The anti-proliferative effect of 15a on MCF-7 cells was associated with G1 cell-cycle arrest. This G1 growth arrest was followed by apoptosis as 15a dose dependently increased phosphatidylserine exposure, PARP cleavage and DNA fragmentation that are hallmarks of apoptotic cell death. Interestingly, 15a activated components of both intrinsic and extrinsic pathways of apoptosis characterized by activation of caspase-8 and -9, mitochondrial membrane depolarization and increase in Bax/Bcl2 ratio. However, use of selective caspase inhibitors revealed that the caspase-8-dependent pathway is the major contributor to 15a-induced apoptosis. Compound 15a also significantly reduced the growth of MCF-7 xenograft tumors in athymic nude mice. Together, 15a could serve as a base for the development of a new group of effective breast cancer therapeutics.
- Dwivedi, Shailendra Kumar Dhar,Samanta, Krishnananda,Yadav, Manisha,Jana, Amit Kumar,Singh, Abhishek Kumar,Chakravarti, Bandana,Mondal, Sankalan,Konwar, Rituraj,Trivedi, Arun Kumar,Chattopadhyay, Naibedya,Sanyal, Sabyasachi,Panda, Gautam
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supporting information
p. 6816 - 6821
(2014/01/06)
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- Intramolecular thermal transformations of N-phthalimidoaziridines: 1,3-dipolar cycloaddition and rearrangements
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The intramolecular thermal cycloaddition of N-phthalimidoaziridines at multiple bonds of substituents with the intermediate formation of azomethine ylides leads to condensed pyrrole derivatives, in which the five-membered ring is adjacent to a five-, six-, or seven-membered ring. Rearrangements, which sometimes become the predominant reactions, compete with cycloaddition. Thus, aziridines with aryl substituents readily isomerize to give imines with a 1,2-shift of the phthalimide group to one of the carbon atoms. Aziridines with one electron-withdrawing substituent probably do not open to give 1,3-dipoles but rather undergo a Cope-type rearrangement involving the three-membered ring and C=O bond of the second substituent. Even in intramolecular reactions, very low activity is found for the cyano group triple bond and aromatic ring bonds as dipolarophiles.
- Kuznetsov,Pan'Kova,Voronin,Vlasenko
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p. 1353 - 1366
(2014/07/21)
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- Highly activatable and environment-insensitive optical highlighters for selective spatiotemporal imaging of target proteins
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Optical highlighters are photoactivatable fluorescent molecules that exhibit pronounced changes in their spectral properties in response to irradiation with light of a specific wavelength and intensity. Here, we present a novel design strategy for a new class of caged BODIPY (4,4-difluoro-4-bora-3a, 4a-diaza-s-indacene) fluorophores, based on the use of photoremovable protecting groups (PRPGs) with high reduction potentials that serve as both a photosensitive unit and a fluorescence quencher via photoinduced electron transfer (PeT). 2,6-Dinitrobenzyl (DNB)-caged BODIPY was efficiently photoactivated, with activation ratios exceeding 600-fold in aqueous solutions. We then combined this photoactivatable fluorophore with a SNAP (mutant of O 6-alkylguanine DNA alkyltransferase) ligand to obtain a small-molecule-based optical highlighter for visualization of protein dynamics, using the well-established SNAP tag technology. As proof of concept, we demonstrate spatiotemporal imaging of the fusion protein of epidermal growth factor receptor (EGFR) with SNAP tag in living cells. We also demonstrate highlighting of cells of interest in live zebrafish embryos, using the fusion protein of histone 2A with SNAP tag.
- Kobayashi, Tomonori,Komatsu, Toru,Kamiya, Mako,Campos, Claudia,Gonzalez-Gaitan, Marcos,Terai, Takuya,Hanaoka, Kenjiro,Nagano, Tetsuo,Urano, Yasuteru
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supporting information; experimental part
p. 11153 - 11160
(2012/09/22)
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- Highly active multidentate alkyne metathesis catalysts: Ligand-activity relationship and their applications in efficient synthesis of porphyrin-based aryleneethynylene polymers
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A series of tris(arylmethyl)ammonium-coordinated molybdenum(VI) propylidyne catalysts was synthesized. Such N-quarternized multidentate catalysts showed high robustness, strong resistance to small alkyne polymerization and significantly enhanced catalytic activity compared to their corresponding tris(arylmethyl)amine-based analogues. The high activity of these new catalysts also enabled the efficient synthesis of ethynylene-bridged porphyrin-based arylene ethynylene polymers via alkyne metathesis, which represents a highly efficient, defect-free, viable approach for the synthesis of this class of intriguing polymers. Copyright
- Jyothish, Kuthanapillil,Wang, Qi,Zhang, Wei
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supporting information
p. 2073 - 2078,6
(2020/09/02)
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