- Enantioselective Synthesis of D -α-(Uracil-5-yl)glycine Derivatives and Their Racemization-Free Incorporation into a Model Peptide
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An efficient asymmetric synthesis of D-α-(uracil-5-yl)glycine derivatives using an enzymatic dynamic kinetic resolution of D,L-hydantoin intermediates with an immobilized D-hydantoinase (D-Hyd-1) is described. In addition, mild conditions for a racemization-free solid-phase peptide synthesis (SPPS) using the Fmoc strategy have been found.
- Weckenmann, Nicole M.,Nachtsheim, Boris J.
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- A structure-specific small molecule inhibits a miRNA-200 family member precursor and reverses a type 2 diabetes phenotype
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MicroRNA families are ubiquitous in the human transcriptome, yet targeting of individual members is challenging because of sequence homology. Many secondary structures of the precursors to these miRNAs (pri- and pre-miRNAs), however, are quite different. Here, we demonstrate both in vitro and in cellulis that design of structure-specific small molecules can inhibit a particular miRNA family member to modulate a disease pathway. The miR-200 family consists of five miRNAs, miR-200a, -200b, -200c, -141, and -429, and is associated with type 2 diabetes (T2D). We designed a small molecule that potently and selectively targets pre-miR-200c's structure and reverses a pro-apoptotic effect in a pancreatic β cell model. In contrast, an oligonucleotide targeting the RNA's sequence inhibited all family members. Global proteomics and RNA sequencing analyses further demonstrate selectivity for miR-200c. Collectively, these studies establish that miR-200c plays an important role in T2D, and small molecules targeting RNA structure can be an important complement to oligonucleotides.
- Abegg, Daniel,Adibekian, Alexander,Aikawa, Haruo,Disney, Matthew D.,Haniff, Hafeez S.,Knerr, Laurent,Lemurell, Malin,Liu, Xiaohui,Meyer, Samantha M.,Tong, Yuquan
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p. 300 - 10,311
(2022/02/17)
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- Synthesis of 5-hetaryluracil derivatives via 1,3-dipolar cycloaddition reaction
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1,3-Dipolar cycloaddition is a convenient method for construction of various heterocyclic systems. We applied this method for the synthesis 5-hetaryluracil derivatives where substituted uracils played the role of 1,3-dipoles or dipolarophiles. Treatment of the nitrile oxide derived from 5-formyluracil and substituted alkenes gave the appropriate 5-(4,5-dihydroisoxazol-3-yl)pyrimidine-2,4(1H,3H)-diones, which by oxidation with N-bromosuccinimide were transformed into appropriate 5-(isoxazol-3-yl)uracils. When 5-cyanouracil was used as a dipolarophile in the reaction with nitrile oxides, generated from aromatic aldoximes, several 5-(1,2,4-oxadiazol-5-yl)uracils were obtained. An alternative reaction of 5-formyluracil with an excess of nitriles in the presence of cerium ammonium nitrate as an oxidant gave 1,2,4-oxadiazol-3-yl derivatives in moderate yields. (Chemical Equation Presented).
- Jakubiec, Dominika,Przypis, ?ukasz,Suwiński, Jerzy W.,Walczak, Krzysztof Z.
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p. 149 - 161
(2017/02/19)
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- The arylimines of 2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carbaldehyde: Synthesis and their application in 1,3-dipolar cycloaddition reaction
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(Chemical Equation Presented) A number of aldimines have been obtained in very good yield in reaction of 5-formyl-1,3-dimethyluracil with various substituted anilines in boiling methanol. Selected aldimines were treated with nitrile oxides generated from 4-chlorobenzaldoxime or 4-methylbenzaldoxime forming the appropriate 1,3-cycloadducts in moderate yields.
- Osyda, Dominika,Motyka, Radoslaw,Walczak, Krzysztof Z.
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body text
p. 1280 - 1284
(2010/03/23)
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- Gonadotropin releasing hormone receptor antagonists
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The present invention relates to Gonadotropin Releasing Hormone (“GnRH”) (also known as Leutinizing Hormone Releasing Hormone) receptor antagonists.
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Page/Page column 22
(2010/02/15)
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- Stereoselective routes to substituted β-amino carbonyl compounds via heterodiene [4π+2π] cycloadditions of auxiliary-based C2 symmetric ketene acetals
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Heterodiene [4π+2π] cycloadditions of (S,S)-4,5-diaryl-2-methylene-1,3-dioxolanes 1 to a series of β-amido-α,β-unsaturated carbonyl compounds are diastereoselective (d.r.≥4:1). The products can be purified by trituration or crystallisation and hydrolysed with acid to generate the corresponding β-amido carbonyl compounds, the overall sequence effecting an auxiliary-based enantioselective conjugate addition of an acetate enolate, leading to β-aminoacid derivatives.
- Leeming, Peter,Ray, Colin A.,Simpson, Stephen J.,Wallace, Timothy W.,Ward, Richard A.
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p. 341 - 352
(2007/10/03)
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- Oxidation of 1,3-dimethylthymine and 1,3-dimethyluracil with oxone in the solid to solid state
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The oxidation of the title substrates with Oxone in the presence of camphor in the solid to solid state afforded a simple and efficient method for epoxidation under mild reaction condition.
- Hong, Yongrae,Chang, Soonjae,Hahn, Bosup,Toda, Fumio
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p. 1455 - 1459
(2007/10/03)
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- Oxidation of 1,3-dimethylthymine with oxone catalyzed by 5,10,15,20-tetrakis (4N-methylpyridiniumyl)porphyrinatomanganese (III) pentaacetate
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The reaction of 1,3-dimethylthymine 2 with KHSO5 (oxone) catalyzed by 5, 10, 15, 20-tetrakis-(4N-methylpyridiniumyl)porphyrinatomanganese (III) pentaacetate 1 [T4MPyPMn (III) (OAc)5] in phosphate buffer gives 1,3-dimethyl-5-hydroxymethyluracil 3, 1,3-dimethyl-5-formyluracil 4, 1,3-dimethyluracil-5-carboxylic acid 5, cis-1,3-dimethylthymine-5,6-glycol 6 and 1,3,5-trimethyl-5-hydroxybarbituric acid 8 in different yields depending on the pH of the reaction medium. Oxidation of the 5-methyl group of 1,3-dimethylthymine to 1,3-dimethyl-5-hydroxymethyluracil 3, 1,3-dimethyl-5-formyluracil 4 and the corresponding acid 5 with oxone catalyzed by T4MPyPMn (III) (OAc)5 may be explained by hydrogen abstraction and recombination mechanism, whereas oxidation of 5,6-double bond of thymine to cis-1,3-dimethylthymine-5,6-glycol 6 and 1,3,5-trimethyl-5-hydroxybarbituric acid 8 may be explained either by electron transfer followed by oxygen atom transfer or by the involvement of hydroxy radicals.
- Chauhan,Gupta, Mamta,Gulati,Nizar
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p. 1267 - 1270
(2007/10/03)
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- Oxidation of nucleic acid related compounds by the peroxodisulfate ion
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The treatment of nucleic acid bases, nucleosides, and nucleotides with peroxodisulfate ion in a phosphate buffer solution at pH 7.0 or water at 70-75°C was investigated. The reaction of thymine and 5-methylcytosine nucleosides and nucleotides resulted in the oxidation of the 5-methyl groups. The oxidation products from 1,3-dimethyluracils and the time-course of the reaction of uracils led to two plausible reaction mechanisms for the oxidation of uracils.
- Itahara,Yoshitake,Koga,Nishino
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p. 2257 - 2264
(2007/10/02)
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- Coupling of 1,3-Dimethylthymine and Adenine with Sodium Peroxodisulfate
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Heating of a solution of 1,3-dimethylthymine and adenine in water containing sodium peroxodisulfate at 80 deg C resulted in the formation of their coupling products.
- Itahara, Toshio
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p. 1105 - 1106
(2007/10/02)
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- Oxidation of Thymines by Peroxosulfate Ions in Water
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Oxidation of thymines by sodium peroxodisulfate in water at 85 deg C gave the corresponding 5-(hydroxymethyl)uracils and 5-formyluracils.The reaction may proceed via thymine cation radicals.On the other hand, oxidation of thymines by potassium peroxomonosulfate in water gave the corresponding cis-5,6-dihydroxy-5,6-dihydrothymines and 5-hydroxy-5-methylbarbituric acids.Furthermore, treatment of thymine with both potassium peroxomonosulfate and hydrogen peroxide in water gave cis-6-hydroperoxy-5-hydroxy-5,6-dihydrothymine.
- Itahara, Toshio,Fujii, Yukiko,Tada, Miki
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p. 3421 - 3424
(2007/10/02)
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- Oxidation of Thymines and Uracils with Sodium Peroxodisulfate
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Reaction of thymines with Na2S2O8 in water resulted in selective oxidation of the methyl group at 5-position of thymines.Oxidation of thymines with Na2S2O8 in hydrochloric acid gave 5-chloro-6-hydroxy-5,6-dihydrothymines and in acetic acid containing NaCl gave 6-acetoxy-5-chloro-5,6-dihydrothymines which were converted to 6-alkoxy-5-chloro-5,6-dihydrothymines with alcohols.The reaction of uracils also gave similar products together with 5-chlorouracils.
- Itahara, Toshio,Ebihara, Reiko,Fujii, Yukiko,Tada, Miki
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p. 1319 - 1322
(2007/10/02)
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- Pyrimidines. 54. Ring Transformation of 5-(2-Carbamoylvinyl)uracil Derivatives to 5-Carbamoylpyridin-2-ones
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Reaction of 5-formyluracil derivatives 1 with (carbamoylmethylene)triphenylphosphorane led to the formation of both the corresponding (Z)- and (E)-5-(2-carbamoylvinyl)uracil derivatives 2 and 3.Upon treatment of the Z isomers 2 with ethanolic sodium ethoxide, a mononuclear heterocyclic rearrangement occurred easily to give 3-(ethoxycarbamoyl)pyridin-6-ones (4) and 3-(N-substituted carbamoyl)pyridin-6-ones (5).Under the analogous conditions, the E isomers 3 were converted into 4 and 5 together with 3-(N-substituted carbamoyl)-1-methylpyridin-6-ones (6).Addition of water to the reaction mixture accelerated the conversion of 3 into 6.Conceivable reaction sequences for the present pyrimidine-to-pyridine transformations are discussed.
- Hirota, Kosaku,Kitade, Yukio,Shimada, Kaoru,Maki, Yoshifumi
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p. 1512 - 1516
(2007/10/02)
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