- Exploring the formation and recognition of an important G-quadruplex in a HIF1α promoter and its transcriptional inhibition by a benzo[c]phenanthridine derivative
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Four putative G-quadruplex sequences (PGSs) in the HIF1α promoter and the 5′UTR were evaluated for their G-quadruplex-forming potential using ESI-MS, CD, FRET, DMS footprinting, and a polymerase stop assay. An important G-quadruplex (S1) has been proven to inhibit HIF1α transcription by blocking AP2 binding. A benzo[c]phenanthridine derivative was found to target the S1 G-quadruplex and induce its conformational conversion from antiparallel to parallel orientation. The transcriptional suppression of HIF1α by this compound was demonstrated using western blotting, Q-RT-PCR, luciferase assay, and ChIP. Our new findings provided a novel strategy for HIF1α regulation and potential insight for cancer therapy.
- Chen, Han,Long, Haitao,Cui, Xiaojie,Zhou, Jiang,Xu, Ming,Yuan, Gu
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Read Online
- Biomimetic synthesis of galantamine: Via laccase/TEMPO mediated oxidative coupling
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Laccase-mediated intramolecular oxidative radical coupling of N-formyl-2-bromo-O-methylnorbelladine afforded a novel and isolable spirocyclohexadienonic intermediate of galantamine. High yield and conversion of substrate were obtained in the presence of the redox mediator 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO). This laccase procedure, with an overall yield of 34%, represents a scalable and environmentally friendly alternative to previously reported syntheses of galantamine based on the use of potassium ferricyanide as an unspecific radical coupling reagent.
- Baratto, Maria Camilla,Bizzarri, Bruno Mattia,Botta, Lorenzo,Pogni, Rebecca,Saladino, Raffaele,Zippilli, Claudio
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p. 10897 - 10903
(2020/03/27)
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- Single-Step Dual Functionalization: One-Pot Bromination-Cross-Dehydrogenative Esterification of Hydroxy Benzaldehydes with CCl 3 Br - A Comparison with Selectfluor
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Bromination of phenolic compounds without directly using molecular bromine possesses much importance. In this article an Ir III /CCl 3 Br-assisted single-step double functionalization of hydroxy benzaldehydes is reported. It involves simultaneous esterification of the aldehyde group and bromination of the aryl ring of phenolic aldehydes in one-pot. The reaction proceeds under mild conditions in the presence of 445 nm blue LED light to obtain highly functionalized bromo hydroxy benzoates in moderate to good yields. In comparison, Selectfluor as an oxidant gives only non-bromo phenolic esters.
- Talukdar, Ranadeep
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supporting information
p. 1713 - 1718
(2019/08/28)
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- PRODRUGS OF KALLIKREIN INHIBITORS
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Disclosed are compounds of formula I, II, and III, and pharmaceutically acceptable salts thereof, which are inhibitors of kallikrein. Also provided are pharmaceutical compositions comprising such a compound, and methods involving use of the compounds and compositions in the treatment and prevention of acquired or hereditary angioedema, or other diseases and conditions characterized by aberrant kallikrein activity. (I) (II) (III)
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Page/Page column 63
(2018/05/24)
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- Synthesis of 5 - methoxy - 4 - hydroxy - 2 - boric acid aldehyde group benzenefrequency alcohol ester (by machine translation)
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The invention provides a method for synthesizing 5 - methoxy - 4 - hydroxy - 2 - boric acid aldehyde group benzenefrequency alcohol ester. In particular, the invention relates to 3, 4 - dimethoxy formaldehyde as raw materials through the bromo to obtain 3, 4 - dimethoxy - 2 - bromophenylacetic formaldehyde, then by removing methyl 5 - hydroxy - 4 - methoxy - 2 - bromophenylacetic formaldehyde, then tert-butyl diphenyl silicon to protect hydroxyl to obtain 5 - tert-butyl diphenyl siloxy - 4 - methoxy - 2 - bromophenylacetic formaldehyde, then in order to glycerol acetal protected aldehyde group, then in BuLi under the action of triisopropyl borate reaction to obtain 5 - methoxy - 4 - tert-butyl diphenyl siloxy - 2 - aldehyde group benzene boric acid, then silicon protecting group to obtain 5 - methoxy - 4 - hydroxy - 2 - boric acid aldehyde group benzene, finally with the pinacone reaction ester to obtain the target product 5 - methoxy - 4 - hydroxy - 2 - boric acid aldehyde group benzenepinacone ester. The invention raw materials are easy, low cost, high yield, easy industrialization. (by machine translation)
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- Synthetic method of 6-Bromoisovanillin
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The invention discloses a synthetic method of 6-Bromoisovanillin. The method comprises the steps of taking ethyl vanillin as a starting material, and preparing the 6-Bromoisovanillin through a methylation reaction, a bromination reaction and an acid decomposition reaction in sequence. After the bromination reaction is finished, first a reacted material is neutralized by using alkali liquor, and then excessive bromine is removed by using sodium thiosulfate. The acid decomposition reaction is first performed at a relatively low temperature, and then is performed at a relatively high temperature. The method provided by the invention takes the ethyl vanillin as the starting material, so the production cost is greatly reduced relative to that of expensive isovanillin. The yield of two steps of the methylation reaction and the bromination reaction can reach more than 95 percent, and more important, the reaction yield of removing ethyl by acid decomposition can reach about 75 percent, so that the total reaction yield can reach 70 percent or more than 70 percent.
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Paragraph 0023; 0024; 0025; 0026; 0027
(2016/10/17)
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- COMPOSITIONS AND USES OF AMIDINE DERIVATIVES
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Use of a compound of formula (I): wherein A, X, Y, R1 and R2 as defined herein, in treating hereditary angioedema is disclosed. A composition containing the compounds, a polar organic solvent or a mixture thereof; and optionally a co-solvent, is also disclosed.
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Page/Page column 144-145
(2016/03/14)
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- METHOD FOR PRODUCING AMIDINE DERIVATIVES
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The invention provides methods and intermediates useful in the synthesis of a compound of formula (I): or a pharmaceutically acceptable salt, solvate, ester or prodrug thereof; wherein the variables are as defined herein.
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- Synthetic studies on Ecteinascidin-743: synthesis of building blocks through Sharpless asymmetric dihydroxylation and aza-Michael reactions
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A practical and an efficient synthesis of three building blocks of tetrahydroisoquinoline alkaloid Ecteinascidin-743 was accomplished, starting from readily available piperonal, 2-methyl anisole, and veratraldehyde. A combination of Vilsmeier-Haack reaction and Sharpless asymmetric dihydroxylation was employed for the synthesis of building blocks A and B whereas a Heck reaction in PEG-2000 and aza-Michael reactions were employed for the synthesis of building block C.
- Chandrasekhar,Reddy, N. Ramakrishna,Rao, Y. Srinivasa
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p. 12098 - 12107
(2007/10/03)
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- PROCESS FOR PREPARATION OF BENZAZEPINE
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This invention discloses a process for manufacture of galanthamine, which involves a stereoselective reduction step to get the desired isomer of galanthamine. The current embodiment also discusses the method for improving the chiral and chemical purity of galanthamine and galanthamine salts.
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Page/Page column 18
(2008/06/13)
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- First synthesis of neoalangiside, a new tetrahydroisoquinoline- monoterpene glucoside with oxygen functions at unusual C1, C2 positions
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The novel structure of neoalangiside, a new tetrahydroisoquinoline- monoterpene glucoside carrying oxygen functions at the unusual C1 and C2 positions, was confirmed by chemical synthesis starting from isovanillin and secologanin.
- Ohmori, Osamu,Takayama, Hiromitsu,Kitajima, Mariko,Aimi, Norio
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p. 1512 - 1513
(2007/10/03)
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- Development of a pilot scale process for the anti-alzheimer drug (-)-galanthamine using large-scale phenolic oxidative coupling and crystallisation-induced chiral conversion
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(-)-Galanthamine has been synthesised using an efficient nine-step procedure, which in large scale affords 12.4 (6.7-19.1)% overall yield. The process improvements and optimization of each step are described. Notable steps include (i) an oxidative phenol coupling and (ii) crystallisation-induced chiral conversion of (±)-narwedine to (-)-narwedine. This is a practical and cost-effective synthesis of (-)-galanthamine which is amenable to pilot plant scale-up to afford sufficient material for use in clinical trials.
- Kueenburg, Bernhard,Czollner, Laszlo,Frohlich, Johannes,Jordis, Ulrich
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p. 425 - 431
(2013/09/08)
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- New kilogram-synthesis of the anti-Alzheimer drug (-)-galanthamine
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A concise, scalable synthesis of (-)-galanthamine, a drug being used for the treatment of Alzheimer's disease, is described. The yield of the critical phenolic coupling step was optimized to 45-50%. For the reduction of the aryl bromide, air-activated LiAlH4 was used and racemic narwedine was converted to (-)-narwedine by a second order asymmetric transformation.
- Czollner, Laszlo,Frantsits, Werner,Kueenburg, Bernhard,Hedenig, Ursula,Froehlich, Johannes,Jordis, Ulrich
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p. 2087 - 2088
(2007/10/03)
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- A concise, scaleable synthesis of narwedine
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A concise, scaleable synthesis of narwedine from 3,4- dimethoxybenzaldehyde is described. The procedure features a simple modification to the Barton phenolic coupling route.
- Chaplin, David A.,Fraser, Neil,Tiffin, Peter D.
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p. 7931 - 7932
(2007/10/03)
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- Synthesis of The Diaza Analogue of Ellagic Acid
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The novel diaza analogue 2 of DNA-gyrase inhibitor ellagic acid 1 was synthesized via the Ullmann coupling of methyl 2-bromo-3-nitroveratrate 6 which, in turn, was prepared by a 7-step synthesis from 2-bromopiperonal 10 requiring a contrived, regiospecifi
- Kanojia, Ramesh M.,Ohemeng, Kwasi A.,Schwender, Charles F.,Barrett, John F.
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p. 8553 - 8556
(2007/10/02)
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- Regioselective cleavage reaction of the aromatic methylenedioxy ring. V. Cleavage with sodium alkoxides-alcohols, potassium tert-butoxide-alcohols, dimsyl anion-methyl alcohol, metallic sodium-alcohols, and sodium cyanide in dipolra aprotic solvents
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The reaction of aromatic methylenedioxy compounds containing electron-withdrawing groups with dimsyl anion-methyl alcohol, potassium tert-butoxide-alcohols, and metallic sodium-alcohols in dimethyl sulfoxide (DMSO), and with sodium alkoxides-alcohols in hexamethylphosphoramide, gave 3- and 4-hydroxybenzene derivatives in good yield by regioselective attack of the alkoxide ions on the methylenedioxy ring. The formation mechanism of alkoxide ions and the effect of DMSO in the cleavage reaction of the methylenedioxy ring are discussed on the basis of proton nuclear magnetic resonance (1H-NMR) spectra. The reactions of aromatic methylenedioxy compounds (3 and 22) with sodium cyanide in dipolar aprotic solvents gave 4-cyano-3-hydroxybenzene derivatives (23 and 24) by regioselective attack of the cyanide ion on the methylenedioxy ring. The reactions of aromatic methylenedioxy compounds (28-30) containing no electron-withdrawing group with MeONa-MeOH in dipolar aprotic solvents gave non-regioselective cleavage products (31 and 34).
- Imakura,Okimoto,Konishi,Hisazumi,Yamazaki,Kobayashi,Yamashita
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p. 1691 - 1696
(2007/10/02)
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- REGIOSELECTIVE CLEAVAGE REACTION OF THE METHYLENEDIOXY RING IN AROMATIC COMPOUNDS CONTAINING ELECTRONWITHDRAWING GROUPS WITH SODIUM ALKOXIDES-ALCOHOLS IN DIMETHYL SULFOXIDE
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The reaction of 6-bromopiperonal (1) with sodium alkoxides (MeONa or PhCH2ONa)-alcohols (MeOH or PhCH2OH), and sodium alkoxides (MeONa, PhCH2ONa or PhONa)-phenol (PhOH) in dimethyl sulfoxide gave 3-hydroxybenzene derivatives (3, 5 and 6) and 4-hydroxybenzene derivative (4), respectively.The reactivity and formational mechanism of various nucleophilic reagents (alkoxide anions) formed from the alcohols and phenol by sodium alkoxides in the regioselective cleavage reactions are discussed.
- Imakura, Yasuhiro,Okimoto, Kazuto,Gorohata, Chizuru,Kobayashi, Shigeru,Kihara, Masaru,Yamashita, Shinsuke
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p. 1067 - 1076
(2007/10/02)
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- Cleavage of the Methylenedioxy Ring. III. Cleavage with Sodium Benzyloxide in Dimethyl Sulfoxide
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Cleavage of the methylenedioxy ring in aromatic formyl (1-3), nitro (4 and 5), and acetyl (30) compounds with N-sodium benzyloxide-benzyl alcohol in dimethyl sulfoxide gave 3-hydroxybenzene derivatives (19, 22-24, 26, 27, and 33).In the case of the acetyl compound 30, the 4-hydroxybenzene derivative (34) was also obtained as a minor product.Regioselective cleavage of the ring in aromatic compounds having electronwithdrawing groups with nucleophilic oxide anions is discussed.Cleavage of the ring in 1-5 and 30 with 2 N sodium methoxide in dimethyl sulfoxide-dimethylformamide was found to be useful for the practical preparation of 3-hydroxybenzene derivatives (6-10 and 31).Keywords - Cleavage of methylenedioxy ring; regioselectivity; piperonals; 3,4-methylenedioxy-nitrobenzene; 3,4-methylenedioxy-acetophenone; sodium methoxide; sodium phenoxide; sodium benzyloxide; dimethyl sulfoxide; dimethylformamide
- Kobayashi, Shigeru,Okimoto, Kazuto,Imakura, Yasuhiro
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p. 1567 - 1573
(2007/10/02)
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- Cleavage of Methylenedioxy Ring. II. Cleavage with Sodium Phenoxide and Methoxide in Dimethyl Sulfoxide
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Regioselective cleavage of the methylenedioxy ring in piperonals (1, 6, and 7) and 3,4-methylenedioxynitrobenzenes (8 and 9) by oxide ions in dimethyl sulfoxide was achieved: the 4-hydroxybenzene derivatives (2, 10-13, and 22) were obtained with the phenoxide ion, while the 3-hydroxybenzene derivatives (4, 18-21, 23, 26, and 29) were obtained with the methoxide or benzyloxide ion.Keywords - cleavage of methylenedioxy ring; regioselectivity; piperonals; 3,4-methylenedioxynitrobenzenes; sodium phenoxide; sodium methoxide; dimethyl sulfoxide; 3-hydroxybenzene derivatives; 4-hydroxybenzene derivatives; NMR spectra
- Kobayashi, Shigeru,Imakura, Yasuhiro,Horikawa, Ritsuko
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p. 1287 - 1293
(2007/10/02)
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