- Cationic Alkynyl Heck Reaction toward Substituted Allenes Using BobCat: A New Hybrid Pd(0)-Catalyst Incorporating a Water-Soluble dba Ligand
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The cationic alkynyl Heck reaction between aryl triflates and alkynes to give substituted allenes is described. Key to the success of this method was the discovery and development of a new hybrid Pd(0)-catalyst, BobCat, that incorporates a water-soluble dba-ligand and biaryl phosphine ligand to provide substituted allenes in good yields under mild reaction conditions.
- Neff, Robynne K.,Frantz, Doug E.
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Read Online
- Semi-rigid (Aminomethyl) piperidine-based pentadentate ligands for Mn(II) complexation
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Two pentadentate ligands built on the 2-aminomethylpiperidine structure and bearing two tertiary amino and three oxygen donors (three carboxylates in the case of AMPTA and two carboxylates and one phenolate for AMPDA-HB) were developed for Mn(II) complexation. Equilibrium studies on the ligands and the Mn(II) complexes were carried out using pH potentiometry,1H-NMR spectroscopy and UV-vis spectrophotometry. The Mn complexes that were formed by the two ligands were more stable than the Mn complexes of other pentadentate ligands but with a lower pMn than Mn(EDTA) and Mn(CDTA) (pMn for Mn(AMPTA) = 7.89 and for Mn(AMPDA-HB) = 7.07).1H and17O-NMR relaxometric studies showed that the two Mn-complexes were q = 1 with a relaxivity value of 3.3 mM?1 s?1 for Mn(AMPTA) and 3.4 mM?1 s?1 for Mn(AMPDA-HB) at 20 MHz and 298 K. Finally, the geometries of the two complexes were optimized at the DFT level, finding an octahedral coordination environment around the Mn2+ ion, and MD simulations were performed to monitor the distance between the Mn2+ ion and the oxygen of the coordinated water molecule to estimate its residence time, which was in good agreement with that determined using the17O NMR data.
- Baranyai, Zsolt,Callegari, Edoardo,Cossi, Maurizio,Fraccarollo, Alberto,Martinelli, Jonathan,Tei, Lorenzo
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- 68Ga-Labelled Tropane Analogues for the Visualization of the Dopaminergic System
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The development of radiometal-labelled pharmaceuticals for neuroimaging could offer great potential due to easier handling during labelling and availability through radionuclide generator systems. Nonetheless, to date, no such tracers are available for positron emission tomography, primarily owing to the challenge of crossing the blood–brain barrier (BBB) and loss of affinity through chelator attachment. We have prepared a variety of 68Ga-labelled phenyltropanes showing that, through a simple hydrocarbon-linker, it is possible to introduce a chelator onto the lead structure while maintaining its high affinity for hDAT (human dopamine transporter) and simultaneously achieving adequate lipophilicity. One of the candidates, [68Ga]Ga-HBED-hexadiyne-tropane, showed an IC50 value of 66 nM, together with a log D7.4 of 0.96. A μPET study in a hemi-parkinsonian rat model showed a fast wash-out of the tracer, and no specific uptake in the brain, thus implying an inability to penetrate the BBB.
- H?seli, Sascha,Holy, Marion,Joksch, Markus,Bergner, Carina,Wree, Andreas,Kurth, Jens,Cankaya, Aylin,Piel, Markus,Krause, Bernd J.,Sitte, Harald H.,R?sch, Frank
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supporting information
p. 804 - 808
(2020/12/15)
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- Metal-free annulative hydrosulfonation of propiolate esters: synthesis of 4-sulfonates of coumarins and butenolides
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An efficient metal-free and cost-effective method for the synthesis of coumarin and butenolide 4-sulfonates (46 examples) has been developed. The reaction involves addition of sulfonic acids to ethyl propiolates followed by lactonization, resulting in direct formation of coumarin and butenolide 4-sulfonates. This methodology has been elaborated to Sonogashira and Suzuki coupling including the synthesis of rac-tolterodine.
- Fernandes, Rodney A.,Gangani, Ashvin J.,Kunkalkar, Rupesh A.
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p. 3970 - 3984
(2020/03/19)
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- Facile Synthesis of 2-Fluorobenzofurans: 5-endo-trig Cyclization of β,β-Difluoro-o-hydroxystyrenes
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Efficient synthetic methods were established for obtaining 2-fluorobenzofurans involving various substituents. Upon being treated with 1,8-diazabicyclo[5.4.0]undec-7-ene under microwave irradiation, the α-unsubstituted β,β-difluoro-o-hydroxystyrenes under
- Morioka, Ryutaro,Fujita, Takeshi,Ichikawa, Junji
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- COMBINATION TREATMENT OF BACTERIAL INFECTION
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The present invention resides in the discovery that combined use of kuraridin (or any one of its analogs) and epicatechin gallate (ECG) can provide heightened level of antimicrobial activity, especially for the suppression of bacteria of the Staphylococcus aureus and Staphylococcal species. Compositions, kits, and methods for the combination use are disclosed.
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Paragraph 0147; 0148
(2020/06/08)
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- Design, synthesis, and evaluation of a water soluble C5-monoketone type curcumin analogue as a potent amyloid β aggregation inhibitor
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A structure activity relationship study of curcumin analogues for the inhibition of amyloid β aggregation is described. Optimization of the o-phenol and olefin spacer resulted in the identification of the C5-monoketone type curcumin analogue AY1319, which
- Hotsumi, Mayumi,Tajiri, Misato,Nikaido, Yuri,Sato, Taki,Makabe, Koki,Konno, Hiroyuki
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supporting information
p. 2157 - 2161
(2019/07/03)
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- Sequential Energy Transfer Catalysis: A Cascade Synthesis of Angularly-Fused Dihydrocoumarins
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An operationally simple one-pot protocol has been developed to enable the conversion of diversely substituted cinnamic acid derivatives into angularly-fused dihydrocoumarins (up to 94%). Inspired by coumarin biosynthesis, this reaction cascade harnesses photochemical E → Z alkene isomerization enabled by energy transfer catalysis using inexpensive thioxanthen-9-one (TX) under irradiation at 402 nm. Subsequent lactonization generates the heterocyclic core prior to a second photosensitization event to induce a [2 + 2] cycloaddition, again mediated by TX. The tetracyclic products are generated efficiently, and proof of the structure was established by X-ray crystallography. Mechanistic investigations, including structural probes and NMR reaction monitoring, support the postulated order of events. The study underscores the synthetic value of inexpensive small-molecule organic photocatalysts in the generation of structural complexity via sequential ?€-bond activation.
- Nevesely, Tomá?,Daniliuc, Constantin G.,Gilmour, Ryan
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supporting information
p. 9724 - 9728
(2019/11/29)
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- 5′-Chloro-2,2′-dihydroxychalcone and related flavanoids as treatments for prostate cancer
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Several flavonoids and their biosynthetic precursor chalcones were designed and synthesized to improve the biological effects of the lead compound 2′-hydroxyflavonone against androgen receptor (AR)-dependent transcriptional stimulation. Newly synthesized chalcones 19 and 26 suppressed AR-dependent transcription as well as DHT-dependent growth stimulation at a low micromolar level. These compounds were also effective against ligand-independent constitutively active mutant AR derived from castration-resistant PCa (CRPC). Compounds 19 and 26 showed broad spectrum antiproliferative activity at 5–10 μM against multiple tumor cell lines including androgen-independent and taxane-resistant prostate cancer as well as a multidrug-resistant subline. Mode of action studies suggested that 19 induced sub-G1 accumulation in PC-3 cells by disrupting the microtubule network without affecting cell cycle progression. Furthermore, the in vivo effectiveness of chalcone 19 was confirmed in a xenograft model antitumor assay. Thus, chalcone 19 has the potential to be a bifunctional lead for treatment of AR-dependent PCa at lower doses as well as AR-independent PCa, including CRPC, at higher doses.
- Saito, Yohei,Mizokami, Atsushi,Tsurimoto, Hiroyuki,Izumi, Kouji,Goto, Masuo,Nakagawa-Goto, Kyoko
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supporting information
p. 1143 - 1152
(2018/09/10)
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- Synthesis and SAR study of new hydroxy and chloro-substituted 2,4-diphenyl 5H-chromeno[4,3-b]pyridines as selective topoisomerase IIα-targeting anticancer agents
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As part of our effort to develop potential topoisomerase IIα (topo IIα) targeting anticancer agents, we systematically designed a new series of hydroxy and chloro-substituted 2,4-diphenyl 5H-chromeno[4,3-b]pyridines. Total eighteen compounds were synthesi
- Magar, Til Bahadur Thapa,Seo, Seung Hee,Kadayat, Tara Man,Jo, Hyunji,Shrestha, Aarajana,Bist, Ganesh,Katila, Pramila,Kwon, Youngjoo,Lee, Eung-Seok
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p. 1909 - 1919
(2018/03/07)
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- Expanding the Reactivity of Donor-Acceptor Cyclopropanes: Synthesis of Benzannulated Five-Membered Heterocycles via Intramolecular Attack of a Pendant Nucleophilic Group
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Lewis-acid-induced domino transformations of donor-acceptor cyclopropanes, possessing a nucleophilic center embedded in a donor group, into functionalized 2,3-dihydrobenzo[b]furans and 2,3-dihydrobenzo[b]thiophenes are reported herein. An unusual switch o
- Ivanova, Olga A.,Andronov, Vladimir A.,Vasin, Vladimir S.,Shumsky, Alexey N.,Rybakov, Victor B.,Voskressensky, Leonid G.,Trushkov, Igor V.
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supporting information
p. 7947 - 7952
(2019/01/04)
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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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- Bioinspired Diastereoconvergent Synthesis of the Tricyclic Core of Palodesangrens via Diels-Alder Reaction, LiAlH4-Mediated Isomerization, and Acid-Mediated Cyclization
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The cyclohexene moiety of the tricyclic 6,7-diaryl-tetrahydro-6H-benzo[c]chromene core of palodesangrens could be assembled in a biomimetic and step-economical fashion by the Diels-Alder reaction between the electron-rich (E)-1,3-butadienylarenes as the diene and the electron-deficient chalcones as the dienophile. During the reduction of ketone to the corresponding alcohol by LiAlH4, the mixture of endo and exo isomers underwent a novel diastereoconvergent LiAlH4-mediated isomerization to install the desired stereochemistry at C10a. Subsequent pyran ring closure under acidic conditions installed the stereochemistry at the remaining C6. Overall, the tricyclic core of palodesangrens could be prepared in three steps and up to 38% yield.
- Songthammawat, Poramate,Wangngae, Sirilak,Matsumoto, Koki,Duangkamol, Chuthamat,Ruchirawat, Somsak,Ploypradith, Poonsakdi
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p. 5225 - 5241
(2018/05/07)
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- COMPOSITIONS FOR INHIBITING ANDROGEN DEPENDENT OR INDEPENDENT PROSTATE CANCER CELLS AND PHARMACEUTICAL FORMULATIONS OF PROSTATE CANCER CONTAINING THE SAME
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PROBLEM TO BE SOLVED: To provide compositions for inhibiting androgen dependent or independent prostate cancer cells which are used for prostate cancer, inhibit activation of androgen receptors, are effective for inhibiting the proliferation of androgen dependent or independent prostate cancer, inhibit the action even if AR-V7 has expressed, and are effective also to anticancer drug resistant cell lines; and to provide pharmaceutical formulations of prostate cancer using the same. SOLUTION: A composition for inhibiting androgen dependent or independent prostate cancer cells comprises an α,β-saturated or unsaturated ketone derivative represented by the following chemical formula (1) or a pharmaceutically acceptable salt thereof. (X- represents a hydrocarbon aromatic ring group or an aromatic heterocyclic group, both or either of Y1- and Y2- are a hydrocarbon aromatic ring group or an aromatic heterocyclic group and the other is a hydrogen atom, Z= represents an atom or a functional group which forms or generates a ketone group, a thioketone group, an imino group, or an oxime group together with a bonding carbon atom, Y3- is a hydrogen atom, a perhalogeno hydrocarbon group or the like.) The pharmaceutical formulation of prostate cancer contains this composition. SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT
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Paragraph 0062
(2018/06/30)
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- Hydrazone–Cu-Catalyzed Suzuki–Miyaura-Type Reactions of Dibromoalkenes with Arylboronic Acids
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We have found that Suzuki–Miyaura-type reactions of dibromoalkenes with arylboronic acids using a hydrazone–Cu catalyst system proceeded smoothly under mild conditions to afford the corresponding internal alkyne derivatives in good yields. Furthermore, we also succeeded in the synthesis of o-allyloxy(ethynyl)benzene derivatives, which are known to be effective precursors of various heterocyclic compounds, through this reaction.
- Watanabe, Kohei,Mino, Takashi,Hatta, Chikako,Ishikawa, Eri,Yoshida, Yasushi,Sakamoto, Masami
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supporting information
p. 3612 - 3619
(2017/07/22)
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- Design, synthesis, and evaluation of curcumin derivatives as Nrf2 activators and cytoprotectors against oxidative death
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Activation of nuclear factor erythroid-2-related factor 2 (Nrf2) has been proven to be an effective means to prevent the development of cancer, and natural curcumin stands out as a potent Nrf2 activator and cancer chemopreventive agent. In this study, we synthesized a series of curcumin analogs by introducing the geminal dimethyl substituents on the active methylene group to find more potent Nrf2 activators and cytoprotectors against oxidative death. The geminally dimethylated and catechol-type curcumin analog (compound 3) was identified as a promising lead molecule in terms of its increased stability and cytoprotective activity against the tert-butyl hydroperoxide (t-BHP)-induced death of HepG2 cells. Mechanism studies indicate that its cytoprotective effects are mediated by activating the Nrf2 signaling pathway in the Michael acceptor- and catechol-dependent manners. Additionally, we verified by using copper and iron ion chelators that the two metal ion-mediated oxidations of compound 3 to its corresponding electrophilic o-quinone, contribute significantly to its Nrf2-dependent cytoprotection. This work provides an example of successfully designing natural curcumin-directed Nrf2 activators by a stability-increasing and proelectrophilic strategy.
- Tu, Zhi-Shan,Wang, Qi,Sun, Dan-Dan,Dai, Fang,Zhou, Bo
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- Compound having acyl coa:cholesterol acyltransferase inhibitory and composition for prevention or treatment of cardiovascular disease comprising thereof
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The present invention relates to: a compound denoted by chemical formula 1 or pharmaceutically acceptable salt thereof; and a composition for preventing or treating cardiovascular diseases containing the same as an effective component. The compound or the
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Paragraph 0072-0074
(2017/08/08)
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- A 2 - [2 - (3-methoxy-phenyl)-ethyl]-phenol synthesis method
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The invention discloses a synthetic method for 2-[2-(3-methoxyphenyl)ethyl]phenol. The method comprises: firstly synthesizing diethyl 3-methoxybenzylphosphonate and 2,2-dimethoxybenzaldehyde, then successively synthesizing 1-(2,2-dimethoxyphenyl)-2-(3-methoxyphenyl)ethylene, 1-(2-phenoxy)-2-(3-methoxyphenyl)ethylene, 1-(2-acetoxphenyl)-2-(3-methoxyphenyl)ethylene and 1-(2-acetoxphenyl)-2-(3-methoxyphenyl)ethane, and finally synthesizing the product 2-[2-(3-methoxyphenyl)ethyl]phenol. The prepared 2-[2-(3-methoxyphenyl)ethyl]phenol product is good in quality and high in yield.
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Paragraph 0019-0020
(2017/01/12)
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- PIPERIDINE-DIONE DERIVATIVES
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The invention provides novel compounds having the general formula (I) and tautomers and pharmaceutically acceptable salts thereof, wherein A1, A2, A3, A4, R1, R4, R5, R6, R7 and R8 are as defined herein, compositions including the compounds and methods of using the compounds.
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Page/Page column 142
(2015/11/10)
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- Design and synthesis of conformationally constrained hydroxylated 4-phenyl-2-aryl chromenopyridines as novel and selective topoisomerase II-targeted antiproliferative agents
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To develop novel selective topoisomerase II inhibitors, we designed and synthesized a series of conformationally constrained hydroxylated 4-phenyl-2-aryl chromenopyridines and evaluated their topoisomerase inhibitory activity and cytotoxicity against thre
- Thapa, Pritam,Jun, Kyu-Yeon,Kadayat, Tara Man,Park, Chanmi,Zheng, Zhi,Thapa Magar, Til Bahadur,Bist, Ganesh,Shrestha, Aarajana,Na, Younghwa,Kwon, Youngjoo,Lee, Eung-Seok
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p. 6454 - 6466
(2015/10/05)
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- First total synthesis of (±)-latifolin and its antioxidant mechanism
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The first total synthesis of (±)-latifolin has been accomplished in six steps and 47.8% overall yield. To understand the relative importance of phenolic O-H and benzhydryl C-H hydrogen on the antioxidant activity of latifolin, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and density functional theory (DFT) studies were carried out. On scavenging DPPH radical in ethanol, the activity of latifolin (1) bearing phenolic hydrogen is remarkably higher than analogue 10 bearing no phenolic hydrogen. Therefore, Phenolic hydrogen is responsible for latifolin's antioxidant activity rather than benzhydryl C-H hydrogen. Furthermore, the 5-OH BDE is lower than 2′-OH and 7-CH BDEs by a DFT calculation, respectively. Based on theoretical results it is definitely concluded that the phenolic 5-OH plays a major role in the antioxidant activity of latifolin. The first total synthesis of (±)-latifolin has been accomplished in six steps and 47.8% overall yield. Based on DPPH-scavenging assay and density functional theory (DFT) studies, the H-atom abstraction of latifolin should take place in the phenolic 5-OH rather than benzhydryl 7-CH.
- Dai, Yihua,Liu, Qiaoling,Li, Zhifang,Chen, Weifeng,Liu, Zhongli
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p. 1287 - 1292
(2015/11/27)
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- Design, synthesis, and evaluation of orally available clioquinol-moracin M hybrids as multitarget-directed ligands for cognitive improvement in a rat model of neurodegeneration in Alzheimer's disease
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A novel series of clioquinol-moracin hybrids were designed and synthesized by fusing the pharmacophores of clioquinol and moracin M, and their activities as multitarget-directed ligands against Alzheimer's disease were evaluated. Biological activity results demonstrated that these hybrids possessed significant inhibitory activities against phosphodiesterase 4D (PDE4D) and Aβ aggregation as well as remarkable antioxidant effects and excellent blood-brain barrier permeability. The optimal compound, 18d (WBQ5187), exhibited excellent PDE4D inhibitory potency (IC50 = 0.32 μM), significant antioxidant effects, appropriate biometal chelating functions, and interesting properties that modulated self- and metal-induced Aβ aggregation. Two-dimensional NMR studies revealed that 18d had significant interactions with Aβ1-42 at the R5, H6, H14, Q15, and F20 residues. Furthermore, this typical hybrid possessed preeminent neuroprotective effects against inflammation in microglial cells. Most importantly, oral administration of 18d·HCl demonstrated marked improvements in cognitive and spatial memory in a rat model of Alzheimer's disease and protected hippocampal neurons from necrosis.
- Wang, Zhiren,Wang, Yali,Wang, Bo,Li, Wenrui,Huang, Ling,Li, Xingshu
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p. 8616 - 8637
(2015/11/25)
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- Synthesis and Characterization of 5-Hydroxy-2-(2-phenylethyl)chromone (5-HPEC) and Its Analogues as Non-nitrogenous 5-HT2B Ligands
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The involvement of the neurotransmitter serotonin (5-HT) in numerous physiological functions is often attributed to the diversity of receptors with which it interacts. Ligands targeting serotonin receptor 2B (5-HT2B) have received renewed interest for their potential to help understand the role of 5-HT2B in migraines, drug abuse, neurodegenerative diseases, and irritable bowel syndrome. To date, most of the ligands targeting 5-HT2B have been nitrogen-containing compounds. The natural product 5-hydroxy-2-(2-phenylethyl)chromone (5-HPEC, 5) has been shown previously to act as a non-nitrogenous antagonist for the 5-HT2B receptor (pKi = 5.6). This report describes further progress on the study of the structure-activity relationship of both naturally occurring and synthetic compounds bearing the 2-(2-phenylethyl)chromone scaffold at the 5-HT2B receptor. The inhibitory activity of the newly synthesized compounds (at 10 μM) was tested against each of the 5-HT2 receptors. Following this assay, the binding affinity and antagonism of the most promising compounds were then evaluated at 5-HT2B. Among all the analogues, 5-hydroxy-2-(2-phenylpropyl)chromone (5-HPPC, 22h) emerged as a new lead compound, showing a 10-fold improvement in affinity (pKi = 6.6) over 5-HPEC with reasonable antagonist properties at 5-HT2B. Additionally, ligand docking studies have identified a putative binding pocket for 5-HPPC and have helped understand its improved affinity. (Figure Presented).
- Williams, Dwight A.,Zaidi, Saheem A.,Zhang, Yan
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p. 1859 - 1867
(2015/09/08)
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- 2-SUBSTITUTED-5-HYDROXY-4H-CHROMEN-4-ONES AS NOVEL LIGANDS FOR THE SEROTONIN RECEPTOR 2B (5-HT2B)
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A family of compounds which function as selective ligands for the serotonin receptor 2B (5-HT2B) is identified. Some of the compounds are synthetic non-natural ligands which have a relatively strong interaction with 5-HT2B compared to naturally occurring compounds (some of which are identified for the first time herein as ligands for 5-HT2B). Because the compounds, both naturally occurring and synthetically produced, function as ligands for 5-HT2B they will have application in, for example, the treatment and/or prevention of nervous system disorders such as Alzheimer's disease.
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Page/Page column 31; 32
(2015/09/22)
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- Stereospecific inhibition of nitric oxide production in macrophage cells by flavanonols: Synthesis and the structure-activity relationship
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To explore the structure-activity relationships on the inhibitory activity of flavanonols against nitric oxide (NO) production in inflammatory cells, we synthesized 19 flavanonols which shared a common 3,5,7-trihydroxychroman scaffold. A range of substitutions was included in the B ring in order to investigate the structure-activity relationship. We also succeeded in isolating stereoisomers from 16 of the flavanonols using chiral column chromatography. The inhibitory effects of these compounds on NO production were examined in RAW 264.7 cells (a murine macrophage-like cell line), which were activated by lipopolysaccharide (LPS). We only observed inhibitory activity against NO production in (2R,3R) stereoisomers, while the inhibitory activities of (2S,3S) stereoisomers were significantly weaker. We also evaluated the free radical scavenging potential of the flavanonols using 1,1-diphenyl-2-picrylhydrazyl (DPPH). Each stereoisomer indicated the equivalent DPPH scavenging potential as expected. The radical scavenging activity was not correlated with the inhibitory activity against NO. The inhibition of NO production by flavanonols is stereospecific and cannot simply be explained by their radical scavenging activity. We propose the possible existence of a 'target' molecule for flavanonols which is involved in the production and/or regulation of NO in RAW 264.7 cells.
- Jiang, Wen-Jun,Ishiuchi, Kan'Ichiro,Furukawa, Megumi,Takamiya, Tomoko,Kitanaka, Susumu,Iijima, Hiroshi
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p. 6922 - 6929
(2015/11/11)
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- Total Synthesis of (-)-Isoamericanin A and (+)-Isoamericanol A
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The enantioselective total synthesis of the biologically active 1,4-benzodioxane lignans isoamericanin A (2) and isoamericanol A (3) has been achieved in 11 and 12 steps, respectively. These benzodioxane lignan natural products, and others that contain 9-hydroxymethyl group, show a wide range of biological properties. The 1,4-benzodioxane ring was formed by an acid-catalysed cyclisation, which gave the desired trans isomer exclusively. This method will allow the synthesis of a number of benzodioxane compounds containing a 9-hydroxymethyl group The total syntheses of (-)-isoamericanin A and (+)-isoamericanol A are described. The key steps were a Mitsunobu etherification and the acid-catalysed formation of the 1,4-benzodioxane moiety with exclusive formation of the desired trans isomer.
- Pilkington, Lisa I.,Barker, David
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p. 1037 - 1046
(2015/10/05)
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- Total synthesis of (-)-isoamericanin A and (+)-isoamericanol A
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The enantioselective total synthesis of the biologically active 1,4-benzodioxane lignans isoamericanin A (2) and isoamericanol A (3) has been achieved in 11 and 12 steps, respectively. These benzodioxane lignan natural products, and others that contain 9-hydroxymethyl group, show a wide range of biological properties. The 1,4-benzodioxane ring was formed by an acid-catalysed cyclisation, which gave the desired trans isomer exclusively. This method will allow the synthesis of a number of benzodioxane compounds containing a 9-hydroxymethyl group The total syntheses of (-)-isoamericanin A and (+)-isoamericanol A are described. The key steps were a Mitsunobu etherification and the acid-catalysed formation of the 1,4-benzodioxane moiety with exclusive formation of the desired trans isomer. Copyright
- Pilkington, Lisa I.,Barker, David
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p. 1037 - 1046
(2014/03/21)
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- A concise total synthesis of biologically active frutinones via tributylphosphine-catalyzed tandem acyl transfer-cyclization
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A concise and step-economical total synthesis of biologically active frutinones has been achieved. Tributylphosphine (PBu3) efficiently induced the tandem acyl transfer-cyclization of carbonates 5 to afford 3-methoxycarbonylflavone derivatives 4 in excellent yields. Finally, concomitant deprotection and lactonization under acidic conditions furnished the desired frutinones A (1a), B (1b), and the proposed structure of frutinone C (1c).
- Yoshida, Masahito,Saito, Koya,Fujino, Yuta,Doi, Takayuki
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supporting information
p. 3452 - 3458
(2014/05/06)
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- Concise approach to 1,4-dioxygenated xanthones via novel application of the Moore rearrangement
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The rapid synthesis of 1,4-dioxygenated xanthones and related natural products employing the Moore rearrangement as a key transformation has been developed. The approach features an acetylide stitching step to unite a substituted squaric acid with a protected hydroxy benzaldehyde derivative to provide a key intermediate that undergoes facile Moore rearrangement to deliver a hydroxymethyl aryl quinone. Subsequent oxidation, hydroxy group deprotection and cyclization then affords highly functionalized xanthones. The utility of the approach was demonstrated by its application to a concise and efficient synthesis of the naturally-occurring xanthone 1. The structure of a natural product that had been named dulcisxanthone C was also corrected to that of the xanthone 1.
- Nichols, Alexander L.,Zhang, Patricia,Martin, Stephen F.
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experimental part
p. 7591 - 7597
(2012/09/21)
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- CONJUGATED AROMATIC COMPOUND, OPTICAL MATERIAL, AND OPTICAL ELEMENT
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The present invention relates to a conjugated aromatic compound represented by the Formula (1) in claim 1 (in the formula, Ar1 represents a hydrogen atom or an aryl group optionally having a substituent; Ar2 and Ar3 each represent a hydrogen atom or an aryl group optionally having a substituent but at least one of Ar2 and Ar3 represents an aryl group optionally having a substituent; and A represents an aromatic hydrocarbon group) and relates to an optical material containing the conjugated aromatic compound. The conjugated aromatic compound and the optical material have characteristics of a high chromatic aberration correction function, high refractive-index dispersion characteristics (Abbe number (vd)) and high secondary dispersion characteristics (θg,F) (anomalous dispersion characteristics).
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Page/Page column 9
(2013/02/28)
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- HETEROAROMATIC-CONTAINING COMPOUND, OPTICAL MATERIAL AND OPTICAL ELEMENT
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There are provided a heteroaromatic-containing compound represented by the following general formula (1), and an optical material including the heteroaromatic-containing compound. Formula 1 General Formula (1) wherein R1 and R2 are each independently a hydrogen atom or a methyl group, Ar1 is an aryl group which may have a substituent, and A is an aromatic hydrocarbon group. The R1 and R2 can be a hydrogen atom, and Ar1 can be a phenyl group.
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Page/Page column 28-29
(2011/07/30)
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- BITTER TASTE MODULATORS
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The present invention includes antagonists of human type 2 taste receptors (hT2Rs) having structural Formula (I). The present invention also provides compositions containing these antagonists, the use of these antagonists for modulating taste perception, particularly bitter taste, and the method of preparing these antagonists (I).
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Page/Page column 97
(2012/01/06)
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- Pt(IV)-catalyzed generation and [4+2]-cycloaddition reactions of o-quinone methides
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Novel intermolecular and intramolecular generations of ortho-quinone methides and their formal [4+2]-cycloaddition reactions with olefins catalyzed by PtCl4 and AuCl3 under mild conditions have been developed. Good to excellent yields (up to 99%) and diastereoselectivity (up to >99:1) of the chromans were obtained. PtCl4 was found to be effective and compatible with various functional groups present in the substrates. A mechanism accounting for its catalytic cycle is proposed and discussed.
- Radomkit, Suttipol,Sarnpitak, Pakornwit,Tummatorn, Jumreang,Batsomboon, Paratchata,Ruchirawat, Somsak,Ploypradith, Poonsakdi
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supporting information; experimental part
p. 3904 - 3914
(2011/06/22)
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- Phenolic bis-styrylbenzenes as β-amyloid binding ligands and free radical scavengers
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Starting from bisphenolic bis-styrylbenzene DF-9 (4), β-amyloid (Aβ) binding affinity and specificity for phenolic bis-styrylbenzenes, monostyrylbenzenes, and alkyne controls were determined by fluorescence titration with β-amyloid peptide Aβ1-40 and a fluorescence assay using APP/PS1 transgenic mouse brain sections. Bis-styrylbenzene SAR is derived largely from work on symmetrical compounds. This study is the first to describe Aβ binding data for bis-styrylbenzenes unsymmetrical in the outer rings. With one exception, binding affinity and specificity were decreased by adding and/or changing the substitution pattern of phenol functional groups, changing the orientation about the central phenyl ring, replacing the alkene with alkyne bonds, or eliminating the central phenyl ring. The only compound with an Aβ binding affinity and specificity comparable to 4 was its 3-hydroxy regioisomer 8. Like 4, 8 crossed the blood-brain barrier and bound to Aβ plaques in vivo. By use of a DPPH assay, phenol functional groups with para orientations seem to be a necessary, but insufficient, criterion for good free radical scavenging properties in these compounds.
- Flaherty, Daniel P.,Kiyota, Tomomi,Dong, Yuxiang,Ikezu, Tsuneya,Vennerstrom, Jonathan L.
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supporting information; experimental part
p. 7992 - 7999
(2011/03/19)
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- NOVEL HISTIDINE DERIVATIVES
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The present invention is to provide a novel compound which is useful as a pharmaceutical agent such as an analgesic. The present invention is to provide the novel histidine derivative having an excellent analgesic action and the like. The compound of the
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Page/Page column 13
(2010/06/22)
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- Generation of ortho-quinone methides by p-TsOH on silica and their hetero-Diels-Alder reactions with styrenes
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(Chemical Equation Presented) 2-Arylchromans were readily prepared from the hetero-Diels-Alder reactions of styrenes with the ortho-quinone methides (o-QMs) which, in turn, were generated by treating the MOM-protected benzylacetate derivatives with p-TsOH immobilized on silica (PTS-Si) in toluene under mild conditions (0°C to rt). The corresponding chromans were obtained in moderate to excellent yields (42-97%) and in moderate to excellent diastereoselectivity (up to >99:1).
- Batsomboon, Paratchata,Phakhodee, Wong,Ruchirawat, Somsak,Ploypradith, Poonsakdi
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supporting information; experimental part
p. 4009 - 4012
(2009/10/14)
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- Solvent-controlled leaving-group selectivity in aromatic nucleophilic substitution
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(Figure Presented) A solvent-controlled inversion of leaving group ability allows selective access to either of two internal substitution products in SNAr reactions of substrates with competing leaving groups. Application of this principle in a
- Hintermann, Lukas,Masuo, Ritsuki,Suzuki, Keisuke
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supporting information; experimental part
p. 4859 - 4862
(2009/05/31)
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- Sysnthesis of 3-O-acylated epicatechin derivatives via sequential one-pot multi-step reactions
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An effective approach for the synthesis of epicatechin derivatives based on sequential one-pot multi-step reactions is described. Reductive etherification of the disulfanyl derivative was promoted with a catalytic amount of TfOH, providing the cis-substit
- Kitade, Makoto,Tanaka, Hiroshi,Takahashi, Takashi
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scheme or table
p. 183 - 186
(2009/09/08)
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- Synthesis of a new series of chiral tri- and tetradentate ligands and their application in titanium-catalyzed pinacol coupling reaction
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A variety of chiral tridentate and tetradentate ligands, related to each other through stereoelectronic relationship have been synthesized. Homochiral diols and amino alcohols have been used for this purpose. Titanium complexes of these ligands have been prepared and examined for enantioselective pinacol coupling reaction.
- Chatterjee,Joshi
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p. 1475 - 1482
(2008/09/18)
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- Effective synthesis of ortho-substituted triphenol amines via reductive amination
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An efficient synthesis of ortho-substituted triphenolamines via reductive amination is reported. This approach allows access to this increasingly important class of ligands in a structurally systematic way using either commercially or easily synthesizable
- Prins, Leonard J.,Blázquez, Myriam Mba,Kolarovi?, Andrej,Licini, Giulia
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p. 2735 - 2738
(2007/10/03)
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- Preparative monohydroxyflavanone syntheses and a protocol for gas chromatography-mass spectrometry analysis of monohydroxyflavanones
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We describe a facile efficient, and preparative approach for monohydroxyflavanone syntheses. Using this protocol, a hydroxyl is regio-selectively introduced at one carbon of a flavanone A- or B-ring per synthesis. The seven possible isomers were each synthesized from the corresponding monomethoxymethoxylated 2′-hydroxychalcones in acidic solution. These monohydroxyflavanones were characterized using a gas chromatography-mass spectrometry (GC-MS) system that incorporated a DB-5 capillary column. Ours is the first report of a preparative synthetic method during which a single hydroxyl can be selectively added to a flavanone A- or B-ring at any position. We are also the first to develop a procedure that separates the seven isomers by GC and characterizes the mass spectra of the isomers. Both the synthetic method and the GC-MS conditions may become important tools during future flavanone metabolism and oxidation studies.
- Kagawa, Hitoshi,Shigematsu, Asako,Ohta, Shigeru,Harigaya, Yoshihiro
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p. 547 - 554
(2007/10/03)
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- Synthesis, antitumor evaluation, and apoptosis-inducing activity of hydroxylated (E)-stilbenes
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The parallel solution-phase synthesis of a series of 30 monohydroxylated (E)-stilbene analogues is described. In vitro screening revealed low micromolar activity (GI50) against the MDA MB 468 breast cancer cell line. Activity in MDA MB 468 cells correlated with the ability to induce apoptosis following drug treatment by the most potent agents in the series, e.g., 5dy and 5jy, an observation further reinforced by Annexin V-FITC analysis and fluorescence microscopy.
- Lion, Cedric J.,Matthews, Charles S.,Stevens, Malcolm F. G.,Westwell, Andrew D.
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p. 1292 - 1295
(2007/10/03)
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- 3-PHENOXY-4-PYRIDAZINOL DERIVATIVE AND HERBICIDE COMPOSITION CONTAINING THE SAME
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A compound represented by the formula: wherein R1 represents a hydrogen atom, a halogen atom, alkyl group, etc., ???R2 represents a hydrogen atom, a halogen atom, alkyl group, etc., ???R3, R4, R5, R6 and R7 each independently represent a hydrogen atom, a halogen atom, a substitutable alkyl group, a substitutable alkenyl group, alkynyl group, a substitute-able cycloalkyl group, etc., or adjacent two of R3, R4, R5, R6 and R7 may together with the carbon atoms to which the respective substituents are bonded form a ring which may be substituted, ???m and n each independently represent 0 or 1, a salt thereof or an ester derivative thereof; an agricultural chemical containing the same as an active ingredient; and a herbicidal composition containing the compound and a second herbicidally active compound as active ingredients.
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Page 175-176
(2008/06/13)
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- New synthesis of benzo[b]furan and indole derivatives from 1,1-dibromo-1-alkenes using a tandem Pd-assisted cyclization-coupling reaction
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We report a new flexible method for the synthesis of 2-functionalized benzo[b]furans and indoles from readily available o-(2,2-dibromovinyl)-phenol, -aniline or -acetanilide using a tandem Pd-assisted cyclization-coupling reaction.
- Thielges, Sabine,Meddah, Emilie,Bisseret, Philippe,Eustache, Jacques
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p. 907 - 910
(2007/10/03)
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- Bicyclic aromatic compounds and pharmaceutical/cosmetic compositions comprised thereof
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Novel pharmaceutically/cosmetically-active bicyclic aromatic compounds have the structural formula (I): in which Ar1 is a radical having one of the structural formulae (a)-(c): Ar2 is a radical having one of the following formulae (d)-(h): and X is a radical having one of the following formulae (i)-(l): and are useful for the treatment of a wide variety of disease states, whether human or veterinary, for example dermatological, rheumatic, respiratory, cardiovascular and ophthalmological disorders, as well as for the treatment of mammalian skin and hair conditions/disorders.
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Page/Page column 31
(2010/01/31)
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- Synthesis of flavonoids and their effects on aldose reductase and sorbitol accumulation in streptozotocin-induced diabetic rat tissues
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Aldose reductase, the key enzyme of the polyol pathway, and oxidative stress are known to play important roles in the complications of diabetes. A drug with potent inhibition of aldose reductase and oxidative stress, therefore, would be a most promising drug for the prevention of diabetic complications. The purpose of this study was to develop new compounds with these dual-effects through synthesis of chalcone derivatives and by examining the structure-activity relationships on the inhibition of rat lens aldose reductase as well as on antioxidant effects. A series of 35 flavonoid derivatives were synthesized by Winget's condensation, oxidation, and reduction of appropriate acetophenones with appropriate benzaldehydes. The inhibitory activity of these derivatives on rat lens aldose reductase and their antioxidant effects, measured using Cu2+ chelation and radical scavenging activities on 1,1-diphenyl-picrylhydrazyl in-vitro, were evaluated. Their effect on sorbitol accumulation in the red blood cells, lenses and sciatic nerves of streptozotocin-induced diabetic rats was also estimated. Among the new flavonoid derivatives synthesized, those with the 2′,4′-dihydroxyl groups in the A ring such as 2,4,2′,4′-tetrahydroxychalcone (22), 2,2′,4′-trihydroxychalcone (11), 2′,4′-dihydroxy-2,4-dimethylchalcone (21) and 3,4,2′,4′-tetrahydroxychalcone (18) were found to possess the highest rat lens aldose reductase inhibitory activity in-vitro, their IC50 values (concentration of inhibitors giving 50 % inhibition of enzyme activity) being 1.6 × 10-7, 3.8 × 10-7, 4.0 × 10-7 and 4.6 × 10-7 M, respectively. All of the chalcones tested except 3, 18, 23 with o-dihydroxy or hydroquinone moiety showed a weak free radical scavenging activity. In the in-vivo experiments, however, compound 18 with o-dihydroxy moiety in the B ring showed the strongest inhibitory activity in the accumulation of sorbitol in the tissues. It also showed the strongest activity in transition metal chelation and free radical scavenging activity. Of the 35 4,2′-dihydroxyl and 2′,4′-dihydroxyl derivatives of flavonoid synthesized, including chalcone, flavone, flavanone, flavonol and dihydrochalcone, some chalcone derivatives synthesized were found to possess aldose reductase inhibition and antioxidant activities in-vitro as well as inhibition in the accumulation of sorbitol in the tissues in-vivo. 3,4,2′,4′-Tetrahydroxychalcone (18, butein) was the most promising compound for the prevention or treatment of diabetic complications.
- Lim, Soon Sung,Jung, Sang Hoon,Ji, Jun,Shin, Kuk Hyun,Keum, Sam Rok
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p. 653 - 668
(2007/10/03)
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- A new preparation of 2,5-dihydro-1-benzoxepins using Mitsunobu cyclization, and the synthesis of natural radulanins
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Mitsunobu cyclization of o-[4-hydroxy-3-methyl-2(Z)-butenyl]phenol 2a effected selective seven-membered cyclization to give 3-methyl-2,5-dihydro-1- benoxepin 1a. Using this procedure, natural radulanin A and radulanin A methyl ether were synthesized effec
- Yamaguchi, Seiji,Furihata, Katsunori,Miyazawa, Masahiro,Yokoyama, Hajime,Hirai, Yoshiro
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p. 4787 - 4790
(2007/10/03)
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- Direct synthesis of pterocarpans via aldol condensation of phenylacetates with benzaldehydes
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Aldol condensation between phenylacetates and benzaldehydes affords 2,3- diaryl-3-hydroxypropanoates which are convened into pterocarpans via stepwise deprotection and cyclization in moderate to high yields.
- Van Aardt, Theunis G.,Van Rensburg, Hendrik,Ferreira, Daneel
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p. 11773 - 11786
(2007/10/03)
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- Sparteine-mediated enantioselective [2,3]-Wittig rearrangement of allyl ortho-substituted benzyl ethers and ortho-substituted benzyl prenyl ethers
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The (-)-sparteine-mediated enantioselective [2,3]-Wittig rearrangement of N,N-dialkyl-o-allyloxymethylbenzamides and o-substituted benzyl prenyl ethers has been investigated. Enantiomeric excess up to 60% was observed as for the reaction with N,N-diethyl-o-allyloxymetylbenzamide. From the mechanistic investigations, it was suggested that the stereoinformation was introduced at the deprotonation step. Substoichiometric amount of (-)- sparteine (0.2 equiv.) did not decrease the enantioselectivity. Introduction of functional groups other than carbamoyl group did not enhance the enantioselectivity in this rearrangement.
- Kawasaki, Takeshi,Kimachi, Tetsutaro
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p. 6847 - 6862
(2007/10/03)
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- The direct synthesis of isoflavans VIA α-alkylation of phenylacetates
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Deprotonation of oxygenated phenylacetates and quenching of the enolates with oxygenated benzylic electrophiles, afforded 2,3-diarylpropanoates which served as precursors to the isoflavans following consecutive reduction and cyclization steps.
- Versteeg, Marietjie,Bezuidenhoudt, Barend C. B.,Ferreira, Daneel
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p. 1373 - 1394
(2007/10/03)
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