- Chiral Pool Synthesis, Biological Evaluation and Molecular Docking Studies of C-Furanosidic LpxC Inhibitors
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Inhibitors of the bacterial deacetylase LpxC are a promising class of novel antibiotics, being selectively active against Gram-negative bacteria. To improve the biological activity of reported C-furanosidic LpxC inhibitors, the stereochemistry at positions 3 and 4 of the tetrahydrofuran ring was varied. In chiral pool syntheses starting from d-gulono-γ-lactone and d-ribose, a series of (3S,4R)-configured dihydroxytetrahydrofuran derivatives was obtained, of which the (2S,5S)-configured hydroxamic acid 15 ((2S,3S,4R,5S)-N,3,4-trihydroxy-5-(4-{[4-(morpholinomethyl)phenyl]ethynyl}phenyl)tetrahydrofuran-2-carboxamide) was found to be the most potent LpxC inhibitor (Ki=0.4 μm), exhibiting the highest antibacterial activity against E. coli BL21 (DE3) and the D22 strain. Additionally, molecular docking studies were performed to rationalize the obtained structure–activity relationships.
- Dreger, Alexander,Kharwb, Omar,Agoglitta, Oriana,Bülbül, Emre F.,Melesina, Jelena,Sippl, Wolfgang,Holl, Ralph
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Read Online
- Pseudouridines in rRNA helix 69 play a role in loop stacking interactions
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The 1H NMR spectra of RNAs representing E. coli 23S rRNA helix 69 with [1,3-15N]pseudouridine modification at specific sites reveal unique roles for pseudouridine in stabilizing base-stacking interactions in the hairpin loop region. The 2008 Royal Society of Chemistry.
- Desaulniers, Jean-Paul,Chang, Yu-Cheng,Aduri, Raviprasad,Abeysirigunawardena, Sanjaya C.,Santalucia Jr., John,Chow, Christine S.
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Read Online
- S-ANTIGEN TRANSPORT INHIBITING OLIGONUCLEOTIDE POLYMERS AND METHODS
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Various embodiments provide STOPS? polymers that are S-antigen transport inhibiting oligonucleotide polymers, processes for making them and methods of using them to treat diseases and conditions. In some embodiments the STOPS? modified oligonucleotides include an at least partially phosphorothioated sequence of alternating A and C units having modifications as described herein. The sequence independent antiviral activity against hepatitis B of embodiments of STOPS? modified oligonucleotides, as determined by HBsAg Secretion Assay, is an EC50 that is less than 100 nM.
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Paragraph 0063; 0415
(2021/06/22)
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- Synthesis, biological evaluation, and molecular docking studies of deoxygenated C-glycosides as LpxC inhibitors
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The bacterial deacetylase LpxC is a promising target for the development of novel antibiotics being selectively active against Gram-negative bacteria. In chiral pool syntheses starting from D- and L-ribose, a series regio- and stereoisomeric monohydroxyte
- Dreger, Alexander,Hoff, Katharina,Agoglitta, Oriana,Bülbül, Emre F.,Melesina, Jelena,Sippl, Wolfgang,Holl, Ralph
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- Sequential Norrish type II photoelimination and intramolecular aldol cyclization of α-diketones: Synthesis of polyhydroxylated cyclopentitols by ring contraction of hexopyranose carbohydrate derivatives
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The excitation of the innermost carbonyl of nono-2,3-diulose derivatives by irradiation with visible-light initiates a sequential Norrish type II photoelimination and aldol cyclization process that finally gives polyfunctionalized cyclopentitols. The rearrangement has been confirmed by the isolation of stable acyclic photoenol intermediates that can be independently cyclized by a thermal 5-(enolexo)-exo-trig uncatalyzed aldol reaction with high diastereoselectivity. In this last step, the large deuterium kinetic isotope effect found for the 1,5-hydrogen atom transfer seems to indicate that the aldol reaction runs through a concerted pericyclic mechanism. Owing to the ready availability of pyranose sugars of various configurations, this protocol has been used to study the influence of pyranose ring-substituents on the diastereoselectivity of the aldol cyclization reaction. In contrast with other pyranose ring contraction methodologies no transition-metal reagents are needed and the sequential rearrangement occurs simply by using visible light and moderate heating (0 to 60 °C). Copyright
- Alvarez-Dorta, Dimitri,Leon, Elisa I.,Kennedy, Alan R.,Martin, Angeles,Perez-Martin, Ines,Riesco-Fagundo, Concepcion,Suarez, Ernesto
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p. 10312 - 10333
(2013/09/02)
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- Stable analogues of ribose-1-phosphate and methods for treating diabetes and other metabolic disorders
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Novel D-ribose-1-phosphate analogue compounds of formula I, pharmaceutically acceptable prodrugs and salts thereof, and their use as hypoglycemic agents and anticancer agents and regulators of carbohydrate metabolism are useful for the treatment of diabet
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Page/Page column 17
(2010/11/26)
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- PROCESS TO PREPARE MALAYAMYCIN DERIVATIVES
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A process is provided for the preparation of a compound of the general formula (I): wherein R is H or C1-4 alkyl, which comprises treating a compound of the general formula (II): where R" is R or R8CO, R is as defined above, R8
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- Selective Formation of Stable Triplexes Including a TA or a CG Interrupting Site with New Bicyclic Nucleoside Analogues (WNA)
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Triplex-forming oligonucleotides (TFOs) are potential DNA-targeting molecules and would become powerful tools for genomic research. As the stabilization of the TFO is partially provided by hydrogen bonds to purine bases, the most stable triplexes form wit
- Sasaki, Shigeki,Taniguchi, Yosuke,Takahashi, Ryo,Senko, Yusuke,Kodama, Keiichi,Nagatsugi, Fumi,Maeda, Minoru
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p. 516 - 528
(2007/10/03)
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- New approach to 1′C-modified riboside scaffold via stereoselective functionalization of D-(+)-ribonic-γ-lactone [1]
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We describe the preparation and spectroscopic properties of a novel class of nucleoside analogues in which a phenyl sulfonyl methylene group is attached to the 1′-carbon atom of β-D-ribofuranose. The glycosylation of 5.0.(tert-butyldiphenylsilyl)-2,3-O-is
- Alzerreca, Arnaldo
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p. 317 - 320
(2007/10/03)
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- Synthesis of a difluorinated carbasugar from D-ribose via intramolecular nitrone cycloaddition reaction
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Difluorinated carbasugar 3 has been synthesised from D-ribose via an intramolecular nitrone cycloaddition reaction with an overall yield of 22%. Copyright (C) 2000 Elsevier Science Ltd.
- Jiang, Shende,Singh, Gurdial,Batsanov, Andrei S.
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p. 3873 - 3877
(2007/10/03)
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- Chiral 1,4-dicarbonyl-2,3-O-isopropylidene derivatives. Rapid racemization on standing
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1,4-Dicarbonyl-2,3-chiral derivatives are useful synthetic precursors for the preparation of carbocyclic rings but, in many cases, losses of optical purity have been reported. 1-Deoxy-3,4-O-isopropylidene-6-O-trityl- D-erythro-hexo-2,5-diulose and 1-deoxy-3,4-O-isopropylidene-6-O-(tert- butyldiphenylsilyl)-D-erythro-hexo-2,5-diulose were synthesized from D- ribono-1,4-lactone. These compounds were selected to study the epimerizability of 2,3-O-isopropylidene-1,4-dicarbonyl derivatives. It was found that both compounds smoothly epimerize and partially racemize on standing.
- Rodriguez, Juan B.
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p. 2157 - 2170
(2007/10/03)
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- A ribonolactone-based approach to the synthesis of 1'-carbon-substituted thymine ribonucleosides
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Thymine ribonucleosides bearing a carbon substituent at the anomeric position were synthesized starting from D-ribonolactone by way of nucleophilic addition reaction of organolithium reagents and subsequent condensation with trimethylsilylated thymine.
- Hayakawa,Miyazawa,Tanaka,Miyasaka
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p. 297 - 308
(2007/10/02)
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- A synthetic route to 3-C-alkyl (or 3-C-phenyl-) 2,3-dideoxy-D-erythro- pentono-1,4-lactones: Intermediates in the synthesis of 2(3H)-furanones
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A series of 3-C-alkyl- (and 3-C-phenyl-) 2,3-dideoxy-D-erythro-pentono- 1,4-lactones, compounds which are important in the synthesis of modified nucleosides and antibiotic sugars, were synthesized from D-ribonolactone. By a route that proceeded via 5-O-pr
- Raveendranath,Blazis,Agyei-Aye,Hebbler,Gentile,Hawkins,Johnson,Baker
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p. 207 - 223
(2007/10/02)
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