- Synthesis and photophysical properties of isocoumarin-based D-π-A systems
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We prepared a small library of polarity-sensitive fluorescent dyes characterized by an isocoumarin core properly functionalized with a conjugated push-pull system. The key step of the synthesis is based on a regio-selective silver(I)/p-TSA co-catalyzed cyclization of 2-alkynylbenzoates recently optimized in our laboratory. The photophysical properties of isocoumarin-based D-π-A systems have been investigated and a rationale was proposed based on their dipole moments and Hammett constants of the ED and EW groups involved.
- Pirovano, Valentina,Marchetti, Marialaura,Carbonaro, Jessica,Brambilla, Elisa,Rossi, Elisabetta,Ronda, Luca,Abbiati, Giorgio
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Read Online
- Synthesis method of 2-bromo-5-methoxybenzoic acid
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The invention provides a synthesis method of 2-bromo-5-methoxybenzoic acid, which comprises the following steps: dissolving m-methoxybenzoic acid in a halogenated hydrocarbon solvent, and carrying outbromination reaction with a bromination reagent under the actions of a bromination initiator, a cocatalyst and sulfuric acid to obtain a 2-bromo-5-methoxybenzoic acid reaction solution; and pouring the 2-bromo-5-methoxybenzoic acid reaction solution into ice water for quenching, recovering the halogenated hydrocarbon solvent under reduced pressure, performing filtering, and performing recrystallizing with a solvent to obtain a 2-bromo-5-methoxybenzoic acid finished product. According to the synthesis method of the 2-bromo-5-methoxy benzoic acid, provided by the invention, the yield of the prepared 2-bromo-5-methoxy benzoic acid is high.
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Paragraph 0024-0033; 0036
(2021/01/29)
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- A convenient and efficient H2SO4-promoted regioselective monobromination of phenol derivatives using N-bromosuccinimide
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A convenient, rapid H2SO4-promoted regioselective monobromination reaction with N-bromosuccinimide was developed. The desired para-monobrominated or ortho-monobrominated products of phenol derivatives were obtained in good to excellent yields with high selectivity. Regioselective chlorination and iodination were also achieved in the presence of H2SO4 using N-chlorosuccinimide and N-iodosuccinimide, respectively.
- Wu, Yong-Qi,Lu, Hai-Jia,Zhao, Wen-Ting,Zhao, Hong-Yi,Lin, Zi-Yun,Zhang, Dong-Feng,Huang, Hai-Hong
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supporting information
p. 813 - 822
(2020/02/15)
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- Synthesis of novel benzbromarone derivatives designed to avoid metabolic activation
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We synthesized six novel BBR derivatives that were designed to avoid metabolic activation via ipso-substitution and evaluated for their degree of toxicity and hURAT1 inhibition. It was found that all of the derivatives demonstrate lower cytotoxicity in mouse hepatocytes and lower levels of metabolic activation than BBR, while maintaining their inhibitory activity toward the uric acid transporter. We propose that these derivatives could serve as effective uricosuric agents that have much better safety profiles than BBR.
- Ohe, Tomoyuki,Umezawa, Ryutaro,Kitagawara, Yumina,Yasuda, Daisuke,Takahashi, Kyoko,Nakamura, Shigeo,Abe, Akiko,Sekine, Shuichi,Ito, Kousei,Okunushi, Kentaro,Morio, Hanae,Furihata, Tomomi,Anzai, Naohiko,Mashino, Tadahiko
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supporting information
p. 3708 - 3711
(2018/11/02)
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- Cobalt(III)-Catalyzed Construction of Benzofurans, Benzofuranones and One-Pot Orthogonal C?H Functionalizations to Access Polysubstituted Benzofurans
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Benzofuran and benzofuranone derivatives have been synthesized through exclusive 5-exo-dig intramolecular hydroarylation using the amide-directed, cost-effective, high-valent Cp*CoIII-catalytic system. Challenging one-pot, orthogonal C?H functionalizations using two different electrophiles are also reported to afford polysubstituted benzofurans. Several valuable functional group interconversions along with removal of the amide directing group provide a route to access several diversely functionalized benzofurans. The mechanistic study suggests a reversible cobaltation step is operative here. (Figure presented.).
- Bera, Sourav Sekhar,Debbarma, Suvankar,Jana, Sripati,Maji, Modhu Sudan
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supporting information
p. 2204 - 2210
(2018/06/07)
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- METHOD FOR PRODUCING 2-HALOGENATED BENZOIC ACIDS
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The purpose of the present invention is to provide a method for producing 2-halogenated benzoic acids, the method imparting high regioselectivity (high selectivity) and having a shorter reaction time than does the conventional reaction. This method for producing 2-halogenated benzoic acids, in order to achieve the above purpose, is characterized in that benzoic acids and a halogenating agent are reacted in the presence of an alkaline compound, making it possible to highly selectively obtain 2-halogenated benzoic acids.
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Paragraph 0063
(2018/04/20)
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- Urolithin C, a gut metabolite of ellagic acid, induces apoptosis in PC12 cells through a mitochondria-mediated pathway
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Urolithins (Uros), metabolites of ellagitannins (ET) and ellagic acid (EA) produced by gut microbiota, showed better bioavailability and extensive bioactivity, and were considered as the active compounds responsible for the health benefits exerted by ET-containing foodstuffs. Here, we chemically synthesized three Uros including Uros A, B, and C and compared their anti-proliferative activities with that of EA in PC12 cells. MTT assay showed that EA significantly promoted, while Uros significantly inhibited the proliferation of PC12 cells, among which UroC showed the strongest anti-proliferation. UroC treatment actively increased the lactate dehydrogenase (LDH) release and lipid peroxidation malondialdehyde (MDA), stimulated reactive oxygen species (ROS) formation and mitochondrial membrane depolarization, and caused calcium dyshomeostasis. Furthermore, flow cytometry analysis showed that UroC treatment induced apoptosis and S phase cell cycle arrest with increasing UroC concentrations. Consequently, UroC also induced imbalance in the Bcl-2/Bax ratio, which triggered the caspase cascade, thereby shifting the balance in favor of apoptosis, as evidenced by western blotting and real-time PCR. These observations indicated that UroC possessed significantly different anti-proliferation activities from EA, and actively induced cell apoptosis through a mitochondria-mediated pathway.
- Yin, Peipei,Zhang, Jianwei,Yan, Linlin,Yang, Lingguang,Sun, Liwei,Shi, Lingling,Ma, Chao,Liu, Yujun
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p. 17254 - 17263
(2017/03/27)
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- Anthraquinone compound and its preparation method and medical use (by machine translation)
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The invention relates to a anthraquinone compound and its preparation method and medical use, cheap and easy to get to the isophthalic acid as the starting material, through the bromo, hydrolysis, esterification of the obtained intermediate with 2 - bromo - 5 - methoxy acyl chloride condensation, condensation product after hydrolysis, loop, debromination reduction to obtain the target product 1, 5 - dihydroxy - 3 - carboxyl - 9, 10 - anthraquinone. The reaction of the invention cheap, low cost, simple operation, high yield. Anti-tumor activity study results display, artificial synthesis of 1, 5 - dihydroxy - 3 - carboxyl - 9, 10 - anthraquinone has better anti-tumor activity. (by machine translation)
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Paragraph 0006; 0011
(2017/08/30)
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- Urolithin as a Converging Scaffold Linking Ellagic acid and Coumarin Analogues: Design of Potent Protein Kinase CK2 Inhibitors
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Casein kinase2 (CK2) is a ubiquitous, essential, and highly pleiotropic protein kinase; its abnormally high constitutive activity is suspected to underlie its pathogenic potential in neoplasia and other relevant diseases. Previously, using different in silico screening approaches, two potent and selective CK2 inhibitors were identified by our group: ellagic acid, a naturally occurring tannic acid derivative (Ki=20nM) and 3,8-dibromo-7-hydroxy-4-methylchromen-2-one (DBC, Ki=60nM). Comparing the crystallographic binding modes of both ellagic acid and DBC, an X-ray structure-driven merging approach was taken to design novel CK2 inhibitors with improved target affinity. A urolithin moiety is proposed as a possible bridging scaffold between the two known CK2 inhibitors, ellagic acid and DBC. Optimization of urolithinA as the bridging moiety led to the identification of 4-bromo-3,8-dihydroxy-benzo[c]chromen-6-one as a novel, potent and selective CK2 inhibitor, which shows a Ki value of 7nM against the protein kinase, representing a significant improvement in affinity for the target compared with the two parent fragments. Two become one: Comparing the crystallographic binding modes of ellagic acid (red) and 3,8-dibromo-7-hydroxy-4-methylchromen-2-one (DBC; blue), an X-ray structure-driven merging approach to the design of novel casein kinase2 (CK2) inhibitors was taken. Using this strategy, a potent and selective urolithin derivative, 4-bromo-3,8-dihydroxy-benzo[c]chromen-6-one was identified, which exhibits a Ki value of 7nM against CK2.
- Cozza, Giorgio,Gianoncelli, Alessandra,Bonvini, Paolo,Zorzi, Elisa,Pasquale, Riccardo,Rosolen, Angelo,Pinna, Lorenzo A.,Meggio, Flavio,Zagotto, Giuseppe,Moro, Stefano
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p. 2273 - 2286
(2012/04/11)
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- PdII-catalyzed monoselective ortho halogenation of C-H bonds assisted by counter cations: A complementary method to directed ortho lithiation
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(Chemical Equation Presented) When the counterion counts: The yield and selectivity of the title transformation of benzoic acid derivatives were improved greatly by using tetraalkyl ammonium salts as additives (see scheme; monoselectivity: 5:1-18:1). These effects are attributed to the influence of counter cations. The halogenated products are versatile intermediates for the construction of substituted aromatic compounds. DMF=N,N-dimethylformamide.
- Mei, Tian-Sheng,Giri, Ramesh,Maugel, Nathan,Yu, Jin-Quan
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supporting information; experimental part
p. 5215 - 5219
(2009/04/11)
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- First general, direct, and regioselective synthesis of substituted methoxybenzoic acids by ortho metalation
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(Chemical Equation Presented) New general methodology of value in aromatic chemistry based on ortho-metalation sites in o-, m-, and p-anisic acids (1-3) (Scheme 1) is described. The metalation can be selectively directed to either of the ortho positions by varying the base, metalation temperature, and exposure times. Metalation of o-anisic acid (1) with s-BuLi/TMEDA in THF at -78°C occurs exclusively in the position adjacente to the carboxylate. On the other hand, a reversal of regioselectivity is observed with n-BuLi/t-BuOK. With LTMP at 0°C, the two directors of m-anisic acid (2) function in concert to direct introduction of the metal between them while n-BuLi/t-BuOK removes preferentially the proton located ortho to the methoxy and para to the carboxylate (H-4). s-BuLi/TMEDA reacts with p-anisic acid (3) exclusively in the vicinity of the carboxylate. According to these methodologies, routes to very simple methoxybenzoic acids with a variety of functionalities that are not easily accessible by other means have been developed (Table 1).
- Nguyen, Thi-Huu,Chau, Nguyet Trang Thanh,Castanet, Anne-Sophie,Nguyen, Kim Phi Phung,Mortier, Jacques
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p. 3419 - 3429
(2008/02/03)
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- Toward a better understanding on the mechanism of ortholithiation. Tuning of selectivities in the metalation of meta-anisic acid by an appropriate choice of base
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(Chemical Equation Presented) If employed in THF at 0°C, LTMP metalates meta-anisic acid at the doubly activated position. In contrast, n-BuLi/t-BuOK deprotonates position C-4 preferentially at low temperature. Functionalization at C-6 requires protection of the C-2 site beforehand. As a result of these findings, a new mechanism is proposed for the heteroatom-directed ortholithiation of aromatic compounds.
- Nguyen, Thi-Huu,Chau, Nguyet Trang Thanh,Castanet, Anne-Sophie,Nguyen, Kim Phi Phung,Mortier, Jacques
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p. 2445 - 2448
(2007/10/03)
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- Condensed pyrazole derivatives, process for producing the same and use thereof
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Novel pharmaceutical compositions for inhibiting Th2-selective immune response and pharmaceutical compositions for inhibiting cyclooxygenase comprising condensed pyrazole derivatives represented by the general formula (I): or salts thereof.
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- Thioxanthenone antitumor agents
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Compounds having anti-tumour activity are disclosed having the formulawherein: (1) n is 2 or 3;R1 and R2 are independently lower-alkyl;Q is a residue chosen from the group consisting ofCH2NHR3, CH2N(R4)SO2R7, CH2NHCHO, CH=N-Ar,C(O)NR5R6, CH2N(R4)C(O)R7, CH2N(C2H5)CHO,CH2N(R4)P(O)(O-lower-alkyl)2, CH2N=CH-N(R9)(R10),CH2N(R4)C(O)CF3 and CH2N(R4)C(O)OR7;R3 is hydrogen or lower-alkyl;R4 is hydrogen, lower-alkyl or Ar;R5 is hydrogen, lower-alkyl or Ar;R6 is hydrogen or lower-alkyl;R7 is lower-alkyl, or Ar;R8 is hydroxy;Ar is phenyl or phenyl substituted with methyl, methoxy, hydroxy, halogen or nitro; andR9 and R10 are independently lower-alkyl; or(2) Q is a residue chosen from the group consisting of CH2N(R4)SO2R7, CH=N-Ar, C(O)NR5R6, CH2N(R4)C(O)R7, CH2N(R4)P(O)(O-lower-alkyl)2, CH2N(R4)C(O)CF3 and CH2N(R4)C(O)OR7; R8 is hydrogen, lower-alkyl, lower-alkoxy, or hydroxy; Ar is phenyl substituted by hydroxy; and n, R1, R2, R4, R5, R6, and R7 are as defined hereinabove in part (1) with the proviso that one or more of R4, R5, or R7 is Ar; or(3) Q is a residue chosen from the group consisting of CH2N=CH-N(R9)(R10) and CH2N(R4)C(O)CF3 ; R8 is hydrogen, lower-alkyl, lower-alkoxy, or hydroxy; and n, R1, R2, R4, R7, Ar, R9 and R10 are as defined hereinabove in part (1), or a pharmaceutically acceptable acid-addition salt or solvate thereof . Compositions containing the thioxanthenones and methods of treating tumors and cancer in mammals with the thioxanthenones are also disclosed.
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- Method for inhibiting neoplastic cells by exposure to substituted N-cycloalkylmethyl-1-H-pyrazolo (3,4-B) quinolone-4 amines
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A method for inhibiting neoplastic cells and related conditions by exposing them to substituted N-cycloalkylmethyl-1H-pyrazolo?3,4-b!quinolin-4-amines.
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- Lyophilized thioxanthenone antitumor agents
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Disclosed are reconstituted lyophilized formulations for the treatment of mammalian tumors comprising a thioxanthenone antitumor agent in combination with mannitol or sucrose as a stabilizer in a lactate buffer.
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- The Bromination of Phenolic Methyl Ethers with Hydrogen Bromide using Sodium Tungstate and Hydrogen Peroxide as Oxidant
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Sodium tungstate has been found to be an effective catalyst for the nuclear bromination of some aromatic methyl ethers using hydrogen bromide in glacial acetic acid and hydrogen peroxide as the oxidant.
- Bezodis, Paul,Hanson, James R.,Petit, Philippe
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p. 334 - 335
(2007/10/03)
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- Substituted N-cycloalkylmethyl-1H-pyrazolo(3,4-b)quinolin-4 amines and compositions and methods of use thereof
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Substituted N-cycloalkylmethyl-1H-pyrazolo[3,4-b]quinolin-4-amines, pharmaceutical compositions containing them and methods for a) effecting c-GMP-phosphodiesterase inhibition, b) treating heart failure and/or hypertension, c) reversing or reducing nitrate-induced tolerance and d) treating angina pectoris, congestive heart disease and myocardial infarction utilizing them.
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- Thioxanthenone antitumor agents
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1-[[(Dialkylamino)alkyl]amino]-4-substituted-thioxanthen-9-ones are disclosed as antitumor agents. Compositions containing the thioxanthenones and methods of treating tumors and cancer in mammals with the thioxanthenones are also disclosed.
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- Dibenzocyclooctene-, Dibenzochalcocine-, and Diarenochalconinediones
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2,2'-Oxybis-, -thiobis-, and -methylenebisbenzoic esters 2a-c react with methyllithium in ether to give low yields of 5H-dibenzochalcocine-5,7(6H)-diones 6a, 7a, and dibenzocyclooctene-5,7(6H,12H)-dione (8), respectively.Very good yields of such heterocycles with oxygen (6a-h, 37), sulfur (7a-h, 38) and selenium (36) as key atom are obtained when diaryl ethers (21, 22, 25), -sulfides (27, 29, 30), and -selenides (33) that contain 2'-acetyl- (or -propionyl-) and 2-methoxycarbonyl groups are treated with sodium hydride in boiling toluene.Analogously are prepared the dibenzoxonine-11,13(6H,12H)diones 62a-c and 7H-benzonaphthothionine-7,9-(8H)-dione (65) which are expanded by one ring member.In the analogous reaction of a corresponding benzophenone derivative 35, spiro-3(2H),3'-dione (41) is formed in a tandem reaction. - Under phase transfer conditions the dibenzochalcocinediones 6, 7, 36 and also the corresponding nitrogen cycles 5 react to give mixtures of C- (42-45) and O-alkyl derivatives (46-49).Methyllithium and diisobutylaluminium hydride provide the carbinols 50-54.With bromine and SO2Cl2, respectively, the methylene group is mono- or dihalogenated to the products 56, 57; defined nitration was only possible for the oxacycle 6a.
- Hellwinkel, Dieter,Bohnet, Siegbert
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p. 1151 - 1174
(2007/10/02)
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- Total synthesis of ring-c aromatic 18-nor steroid1 1 Abstracted in part from the Ph.D. thesis (1970) of B.G.H.A part of this work appeared in a preliminary communication (see [7]).
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The total synthesis of (±)-11-methoxy-18-nor-5χ and 5β-androsta-8(9),11,13(14)-triene-3,17-dione is reported.
- Chatterjee,Hazra
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p. 2513 - 2519
(2007/10/02)
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