- Synthesis of some novel pyrano[2,3-f]chromenone derivatives
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A new series of pyrano[2,3-f]chromenone derivatives were synthesized starting from resorcinol. Resorcinol reacted with 3-chloropropanoic acid to give 7-hydroxychroman-4-one and reaction of the later compound with 2-methylbut-3-yn-2-ol led to the formation of 7-((2-methylbut-3-yn-2-yl)oxy)chroman-4-one. The obtained compound tolerated the cyclization reaction through Claisen rearrangement by heating in DMF to afford 8,8-dimethyl-2,3-dihydro-4H,8H-pyrano[2,3-f]chromen-4-one. Reaction of the later compound with various aromatic aldehydes gave the title compounds in good yields. All products were evaluated for their cytotoxic activity on the blood tumor cell line K562 and compared to reference drug, etoposide. Most of them exhibited low inhibitory activity against tumor cell line and among them, the compound possessing three methoxy groups on aromatic ring showed better cytotoxic effect.
- Alizadeh, Babak Heidary,Saeedi, Mina,Dehghan, Gholamreza,Foroumadi, Alireza,Shafiee, Abbas
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- Copper-Triggered Bioorthogonal Cleavage Reactions for Reversible Protein and Cell Surface Modifications
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Temporal and reversible control over protein and cell conjugations holds great potential for traceless release of antibody-drug conjugates (ADCs) on tumor sites as well as on-demand altering or removal of targeting elements on cell surface. We herein developed a bioorthogonal and traceless releasable reaction on proteins and intact cells to fulfill such purposes. A systematic survey of transition metals in catalyzing the bioorthogonal cleavage reactions revealed that copper complexes such as Cu(I)-BTTAA and dual-substituted propargyl (dsPra) or propargyloxycarbonyl (dsProc) moieties offered a bioorthogonal releasable pair for reversible blockage and rescue of primary amines and phenol alcohols on small molecule drugs, protein side chains, as well as intact cell surface. For proof-of-concept, we employed such Cu(I)-BTTAA/dsProc and Cu(I)-BTTAA/dsPra pairs as a "traceless linker" strategy to construct cleavable ADCs to unleash cytotoxic compounds on cancer cells in situ and as a "reversible modification" strategy for cell surface engineering. Furthermore, by coupling with the genetic code expansion strategy, we site-specifically modulated ligand-receptor interactions on live cell membranes. Together, our work expanded the transition-metal-mediated bioorthogonal cleavage tool kit from terminal decaging to internal-linker breakage, which offered a temporal and reversible conjugation strategy on therapeutic proteins and cells.
- Wang, Xin,Liu, Yanjun,Fan, Xinyuan,Wang, Jie,Ngai, William Shu Ching,Zhang, Heng,Li, Jiaofeng,Zhang, Gong,Lin, Jian,Chen, Peng R.
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supporting information
p. 17133 - 17141
(2019/11/03)
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- Synthesis of Euchrestifoline Using Iron- and Palladium-Catalyzed C–H Bond Activations
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We describe a short and efficient synthetic route to euchrestifoline. Key steps of our approach are the iron(III)-catalyzed Wacker-type oxidation of a chromene derivative with hexadecafluorophthalocyanine-iron (FePcF16) as catalyst, a palladium(0)-catalyzed Buchwald–Hartwig amination, and the final palladium(II)-catalyzed oxidative cyclization of the resulting diarylamine to the natural product.
- Puls, Florian,Kataeva, Olga,Kn?lker, Hans-Joachim
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p. 4272 - 4276
(2018/08/28)
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- Divergent Syntheses of Carbazole Alkaloids Clausenapin, Indizoline, Claulansine M, and Clausenaline D
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We described the first total syntheses of clausenapin, indizoline, claulansine M, and a novel synthetic route to clausenaline D via divergent method. Key steps involved TFAA-mediated intramolecular acylation to construct the carbazole core and subsequent Claisen rearrangement to generate key intermediates for further elaboration to target molecules.
- Liu, Yizhen,Guo, Yanqin,Ji, Feixiang,Gao, Dong,Song, Chuanjun,Chang, Junbiao
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p. 4310 - 4315
(2016/06/09)
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- NOVEL COMPOUND OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, AND PHARMACEUTICAL COMPOSITION CONTAINING SAME AS ACTIVE INGREDIENT
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The present invention relates to a compound inhibiting Hsp90 and a pharmaceutical composition comprising the same as an active ingredient. The compounds represented by formula 1 and formula 2 of the present invention suppress the expression of Hsp90 so that they can inhibit the accumulation of HIF-1α, the Hsp90 client protein, and also efficiently inhibit the activation of VEGF. In addition, these compounds display low cytotoxicity, so that they can be effectively used as an active ingredient of an anti-cancer agent, a diabetic retinopathy treating agent, and an anti-arthritic agent.
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Paragraph 0247-0250
(2015/07/15)
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- Multidimensional optimization of promising antitumor xanthone derivatives
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A promising antitumor xanthone derivative was optimized following a multidimensional approach that involved the synthesis of 17 analogues, the study of their lipophilicity and solubility, and the evaluation of their growth inhibitory activity on four human tumor cell lines. A new synthetic route for the hit xanthone derivative was also developed and applied for the synthesis of its analogues. Among the used cell lines, the HL-60 showed to be in general more sensitive to the compounds tested, with the most potent compound having a GI50 of 5.1 μM, lower than the hit compound. Lipophilicity was evaluated by the partition coefficient (Kp) of a solute between buffer and two membrane models, namely liposomes and micelles. The compounds showed a log Kp between 3 and 5 and the two membrane models showed a good correlation (r2 = 0.916) between each other. Studies concerning relationship between solubility and structure were developed for the hit compound and 5 of its analogues.
- Azevedo, Carlos M.G.,Afonso, Carlos M.M.,Sousa, Diana,Lima, Raquel T.,Helena Vasconcelos,Pedro, Madalena,Barbosa, Jo?o,Corrêa, Arlene G.,Reis, Salette,Pinto, Madalena M.M.
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p. 2941 - 2959
(2013/07/05)
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- Discovery of a novel series of nonacidic benzofuran EP1 receptor antagonists
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We describe the discovery and optimization of a novel series of benzofuran EP1 antagonists, leading to the identification of 26d, a novel nonacidic EP1 antagonist which demonstrated efficacy in preclinical models of chronic inflammat
- Allan, Amanda C.,Billinton, Andy,Brown, Susan H.,Chowdhury, Anita,Eatherton, Andrew J.,Fieldhouse, Charlotte,Giblin, Gerard M.P.,Goldsmith, Paul,Hall, Adrian,Hurst, David N.,Naylor, Alan,Rawlings, D. Anthony,Sime, Mairi,Scoccitti, Tiziana,Theobald, Pamela J.
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scheme or table
p. 4343 - 4348
(2011/08/06)
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- New synthetic route towards 2,2-dimethylchromene and synthesis of substituted 7-(dimethylpropargyl)chromene
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(Chemical Equation Presented) Trifluoromethansufonic acid (TFA) was found a proper reagent for regioselectively ring closure of resorcinol to afford 7-hydroxy-2,2-dimethyl-2,3-dihydrochromen-4-one 3. The propargylation of 3 gave rise to 2,2-dimethyl-7-(2-methylbut-3-yn-2-yloxy)-2,3-dihydrochromen-4-one 4. Condensation of 4 with substituted phenyl or benzyl Grignard reagents afforded substituted phenyl or benzylidene chromenes 6a-d and 4-(substitutedbenzylidene)- 3,4-dihydro chromenes 8a-e, respectively.
- Alizadeh, Babak H.,Foroumadi, Alireza,Shafiee, Abass
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p. 909 - 912
(2008/09/21)
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- Palladium-catalyzed total synthesis of euchrestifoline using a one-pot Wacker oxidation and double aromatic C-H bond activation
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We describe the total synthesis of euchrestifoline featuring an unprecedented one-pot Wacker oxidation and double aromatic C-H bond activation. The 2008 Royal Society of Chemistry.
- Gruner, Konstanze K.,Knoelker, Hans-Joachim
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scheme or table
p. 3902 - 3904
(2009/06/28)
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- Biomimetic total synthesis of gambogin and rate acceleration of pericyclic reactions in aqueous media
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A significant rate acceleration of a Claisen rearrangement and of a Claisen/Diels-Alder reaction cascade sequence was observed in the presence of water. This reaction sequence was used in a total synthesis of gambogin (1) from a tricyclic dialkene 3 via 2
- Nicolaou,Xu, Hao,Wartmann, Markus
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p. 756 - 761
(2007/10/03)
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- Biomimetically Inspired Total Synthesis and Structure Activity Relationships of 1-O-Methyllateriflorone. 6π Electrocyclizations in Organic Synthesis
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The total synthesis of 1-O-methyllateriflorone (2) is described. The construction of the cage-like domain of the molecule involved a biomimetic Claisen/Diels-Alder cascade, whereas the novel spiroxalactone framework was generated by an intramolecular Mich
- Nicolaou,Sasmal, Pradip K.,Xu, Hao
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p. 5493 - 5501
(2007/10/03)
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- Continuous processing to control a potentially hazardous process: Conversion of aryl 1,1-dimethylpropargyl ethers to 2,2-dimethylchromenes (2,2-dimethyl-2H-1-benzopyrans)
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The thermal Claisen rearrangement of 4-cyanophenyl 1,1-dimethylpropargyl ether (4) to 6-cyano-2,2-dimethylchromene (5), (6-cyano-2,2-dimethyl-2H-1-benzopyran), which is used in the synthesis of a potassium channel activator drug candidate, BMS-180448, created a significant process development issue. The resulting large heat release in this conversion posed not only a safety risk but could also cause product degradation if done in a batch-wise manner. The solution was to exploit the high surface-to-volume ratio of a plug-flow reactor that would maximize the heat transfer, thereby permitting tight and responsive temperature with better reaction control. In the course of successfully testing the plug-flow concept on "micro"-flow scale (gram quantity) and "kilo"-flow scale (~10 kg), a generalized mathematical model capable of predicting the reaction performance based on the physical properties of any given plug-flow reactor was generated. The model provides requisite information to design and operate a plug-flow reactor of any size for this reaction. This model would optimize reaction conditions for an acquired reactor system capable of producing ~7 kg/h of the dimethylchromene. Application of plug-flow reactor technology enabled production of high quality 2,2-dimethylchromenes in good yield (>98 mol %) without the use of solvents and with virtually no waste streams.
- Bogaert-Alvarez, Ricardo J.,Demena, Paul,Kodersha, Gus,Polomski, Robert E.,Soundararajan,Wang, Steve S. Y.
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p. 636 - 645
(2013/09/07)
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- A fully synthetic route the neurotrophic illicinones: Syntheses of tricycloillicinone and bicycloillicinone aldehyde
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Tricycloillicinone (1) and bicycloillicinone asaronacetal (2) were both isolated from extracts of the wood of Illicium tashiroi. These compounds were found to enhance the action of choline acetyltransferase, which catalyzes the synthesis of acetylcholine from its precursor. Since one of the characteristic symptoms of Alzheimer's disease involves degeneration of cholinergic neurons, resulting in markedly reduced levels of acetylcholine, compounds with the properties of 1 or 2 could well serve as agents in the treatment of such disorders. In this paper, we report the total synthesis of I and the construction of the core structure 3 of 2. The tricycloillicinone synthesis employed a novel strategy to control the regiochemistry of two ortho Claisen rearrangements. A sulfonyl group introduced at C2 of an allyl group effectively suppressed its unwanted rearrangement to the para position (23 → 24). Subsequently, ortho Claisen rearrangement was conducted using a reverse O- prenylated derivative 31 to furnish the desired 32, selectively. 32 was used as a common precursor for the syntheses of both 1 and 3. The application of Corey-Snider oxidative cyclization and the Barton-McCombie deoxygenation provided a direct route to 1. For bicycloillicinone aldehyde 3, a new tandem reaction using the Et2AlCN to construct the cage structure (39 → 41) was employed. Flexible syntheses of the polycyclic illicinones should provide access to analogous structures for future biological and SAR studies.
- Pettus, Thomas R.R.,Inoue, Masayuki,Chen, Xiao-Tao,Danishefsky, Samuel J.
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p. 6160 - 6168
(2007/10/03)
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- A Convenient Synthesis of 6-Substituted-2,2-dimethyl-2H-1-benzopyrans
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Various 2,2-dimethyl-6-functional-2H-1-benzopyrans were prepared via a halogen-metal exchange reaction followed by treatment with electrophiles. These 6-functionalized chromenes are important synthetic intermediates for preparation of benzopyran-based pot
- Ding, Charles Z.
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p. 4267 - 4273
(2007/10/03)
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- Process for the preparation of intermediates useful in the preparation of pyranyl cyanoguanidine derivatives
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A process for preparing compounds of the formula STR1 where a, b, c, R1, R2, and R3 are as defined herein including the step of alkylating a phenol of formula STR2 with an acetylene of formula STR3 where X is chlorine; bro
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- Improved Synthesis of Aryl 1,1-Dimethylpropargyl Ethers
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An efficient, general, and practical synthesis of aryl 1,1-dimethylpropargyl ethers has been developed.
- Godfrey, Jollie D.,Mueller, Richard H.,Sedergran, Thomas C.,Soundarajan, Nachimuthu,Colandrea, Vincent J.
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p. 6405 - 6408
(2007/10/02)
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