- Synthesis of extended uridine phosphonates derived from an allosteric p2y2 receptor ligand
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In this study we report the synthesis of C5/C6-fused uridine phosphonates that are structurally related to earlier reported allosteric P2Y2 receptor ligands. A silyl-Hilbert- Johnson reaction of six quinazoline-2,4-(1H, 3H)-dione-like base moie
- Song, Lijun,Risseeuw, Martijn D. P.,Karalic, Izet,Barrett, Matthew O.,Brown, Kyle A.,Harden, T. Kendall,Van Calenbergh, Serge
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- CYCLIC DINUCLEOTIDE COMPOUND AND USES THEREOF
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Provided are a compound of formula (I), an optical isomer thereof, a pharmaceutically acceptable salt thereof, uses of said compound acting as a STING agonist.
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Paragraph 0331-0333
(2021/11/05)
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- Synthesis and in vitro anticancer activity of penaresidin-related stereoisomeric analogues
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A straightforward route to penaresidin-based derivatives with an unsubstituted alkyl side chain was developed. To construct these stereoisomeric azetidene-derived alkaloids, [3,3]-sigmatropic rearrangements followed by late stage olefin cross metathesis and an intramolecular nucleophilic type substitution were involved as the key transformations. The protected D-ribofuranose was chosen as the sole chiral source. The ability of target molecules to inhibit cancer cells proliferation was evaluated on a panel of five malignant cell lines.
- Bodnár, Gergo,Kuchár, Juraj,Martinková, Miroslava,Nosálová, Natália,Pilátová, Martina Bago,Raschmanová, Jana ?paková
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- NOVEL PROCESS FOR MAKING ALLOFURANOSE FROM GLUCOFURANOSE
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The present invention relates to the manufacture of allofuranose from glucofuranose as defined in the description and in the claim. Allofuranos is an intermediate in the manufacture of oligonucleotides which can be used as a medicament.
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- From Oxygen to Sulfur and Back: Difluoro -H-phosphinothioates as a Turning Point in the Preparation of Difluorinated Phosphinates: Application to the Synthesis of Modified Dinucleotides
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A simple, two-step procedure to convert α,α-difluorinated H-phosphinic acids into the corresponding H-phosphinothioates is described. The usefulness of these species is demonstrated by their transformation into difluorinated phosphinothioyl radicals and their addition onto alkenes. Additionally, sequential treatment of H-phosphinothioates by a strong base and a primary alkyl iodide constitutes an alternate route to the formation of the C-P bond. Both methods efficiently deliver difluorinated phosphinothioates. Similar reactions carried out with the fully oxygenated counterparts clearly indicate the superiority of the sulfur-based species and emphasize the crucial role played by sulfur in the construction of the second C-P bond. Oxidation easily transforms the thereby obtained phosphinothioates into the corresponding phosphinates. The whole strategy is applied to the stereoselective preparation of dinucleotide analogues featuring either a difluorophosphinothioyl or a difluorophosphinyl unit linking the two furanosyl rings.
- Zhang, Jun,Lambert, Emilie,Xu, Ze-Feng,Brioche, Julien,Remy, Pauline,Piettre, Serge R.
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p. 5245 - 5260
(2019/05/10)
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- Anaerobic 5-Hydroxybenzimidazole Formation from Aminoimidazole Ribotide: An Unanticipated Intersection of Thiamin and Vitamin B12 Biosynthesis
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Comparative genomics of the bacterial thiamin pyrimidine synthase (thiC) revealed a paralogue of thiC (bzaF) clustered with anaerobic vitamin B12 biosynthetic genes. Here we demonstrate that BzaF is a radical S-adenosylmethionine enzyme that catalyzes the remarkable conversion of aminoimidazole ribotide (AIR) to 5-hydroxybenzimidazole (5-HBI). We identify the origin of key product atoms and propose a reaction mechanism. These studies represent the first step in solving a long-standing problem in anaerobic vitamin B12 assembly and reveal an unanticipated intersection of thiamin and vitamin B12 biosynthesis.
- Mehta, Angad P.,Abdelwahed, Sameh H.,Fenwick, Michael K.,Hazra, Amrita B.,Taga, Michiko E.,Zhang, Yang,Ealick, Steven E.,Begley, Tadhg P.
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p. 10444 - 10447
(2015/09/28)
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- SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF
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Disclosed herein are nucleosides, nucleotides and nucleotide analogs, methods of synthesizing the same and methods of treating diseases and/or conditions such as a Picornavirus and/or Flaviviridae infection with one or more nucleosides, nucleotides and nucleotide analogs.
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- SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF
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Disclosed herein are nucleosides, nucleotide analogs, methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a Filoviridae virus infection with one or more nucleosides and/or nucleotide analogs.
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- SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF
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Disclosed herein are nucleosides, nucleotides and nucleotide analogs, methods of synthesizing the same and methods of treating diseases and/or conditions such as a Coronaviridae virus, a Togaviridae virus, a Hepeviridae virus and/or a Bunyaviridae virus infection with one or more nucleosides, nucleotides and nucleotide analogs.
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- Towards stable di-carba analogues of guanofosfocins
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Guanofosfocins are strong inhibitors of chitin synthases, but also very prone to hydrolytic cleavage. Two advanced intermediates 15 and 20 for the synthesis of stable di-carba-guanofosfocins were prepared via ester 11. Acylation of the allylic C-glycoside
- Duchek, Jan,Huang, Mu-Hua,Vasella, Andrea
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supporting information; scheme or table
p. 2940 - 2942
(2011/06/23)
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- Synthesis and biological evaluation of 2′,4′- and 3′,4′-bridged nucleoside analogues
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Most nucleosides in solution typically exist in equilibrium between two major sugar pucker forms, N-type and S-type, but bridged nucleosides can be locked into one of these conformations depending on their specific structure. While many groups have researched these bridged nucleosides for the purpose of determining their binding affinity for antisense applications, we opted to look into the potential for biological activity within these conformationally-locked structures. A small library of 2′,4′- and 3′,4′-bridged nucleoside analogues was synthesized, including a novel 3′,4′- carbocyclic bridged system. The synthesized compounds were tested for antibacterial, antitumor, and antiviral activities, leading to the identification of nucleosides possessing such biological activities. To the best of our knowledge, these biologically active compounds represent the first example of 2′,4′-bridged nucleosides to demonstrate such properties. The most potent compound, nucleoside 33, exhibited significant antiviral activity against pseudoviruses SF162 (IC50 = 7.0 μM) and HxB2 (IC50 = 2.4 μM). These findings render bridged nucleosides as credible leads for drug discovery in the anti-HIV area of research.
- Nicolaou,Ellery, Shelby P.,Rivas, Fatima,Saye, Karen,Rogers, Eric,Workinger, Tyler J.,Schallenberger, Mark,Tawatao, Rommel,Montero, Ana,Hessell, Ann,Romesberg, Floyd,Carson, Dennis,Burton, Dennis
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scheme or table
p. 5648 - 5669
(2011/10/31)
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- Conformationally constrained analogues of diacylglycerol (DAG). Part 19: Asymmetric syntheses of (3R)- and (3S)-3-hydroxy-4,4-disubstituted heptono-1,4-lactones as protein kinase C (PK-C) ligands with increased hydrophilicity
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The stereospecific introduction of (R)- and (S)-OH groups at position C-3 of two diacylglycerol γ-lactones (DAG-lactones) previously identified as strong protein kinase C (PK-C) ligands is presented. The compounds were designed to investigate whether the extra OH group in a specific orientation could establish an additional hydrogen bond with the C1 domain of PK-C, thus providing a DAG analogue with reduced lipophilicity. The OH groups were introduced following two different diastereoselective multistep syntheses starting from diacetone-D-glucose. The PK-C binding affinities for the new compounds were weaker in comparison to those of the parent compounds, suggesting that the extra OH does not engage efficiently in hydrogen bonding at the receptor.
- Nacro, Kassoum,Lee, Jeewoo,Barchi Jr., Joseph J,Lewin, Nancy E,Blumberg, Peter M,Marquez, Victor E
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p. 5335 - 5345
(2007/10/03)
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- Synthesis of 2-chloro-2'-5'-dideoxy-5'-difluoromethylphosphinyladenosine: A nonhydrolyzable isosteric, isopolar analog of 2-chlorodeoxyadenosine monophosphate
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2-Chloro-2'-5'-dideoxy-5'-difluoromethylphosphinyladenosine (5) was synthesized in thirteen steps from 3-O-benzyl-1,2-O-isopropylidene-α-D-ribofuranoside (1), a carbohydrate which is substituted differently at the 2- and 3-positions, making possible selective deprotection and reductive deoxygenation at the 2'-position of a nucleoside subsequent to glycosylation. Purine nucleoside phosphonate 5 is an analog of the monophosphate ester of the potent, clinically effective immunomodulatory agent 2-chlorodeoxyadenosine (2-CdA), and was synthesized to present a potential means of circumventing drug resistance in target immune cells.
- Levy, Stuart G.,Wasson, D. Bruce,Carson, Dennis A.,Cottam, Howard B.
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p. 843 - 846
(2007/10/03)
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- The use of free radical cyclization in the synthesis of compounds related to the mannostatins
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A study of the potential use of 5-exo free radical cyclizations in the synthesis of carbocyclic compounds related to the mannostatins 1 and 2 is described. The dithioacetal 8 was prepared and the methyl oxime moiety utilised as an intramolecular radical t
- Ingall,Moore,Roberts
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p. 2155 - 2162
(2007/10/02)
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- Radical Cyclisation Reactions Leading to Polyhydroxylated Cyclopentane Derivatives: Synthesis of (1R,2R,3S,4R)- and (1S,2S,3R,4S)-4-Hydroxyethylcyclopentane-1,2,3-triol
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The tetrol (-)-1 has been prepared from a derivative of (D)-allose 3.The stereoselective carbocyclization reaction (8->11) formed the key step in this sequence.The enantiomeric cyclopentane derivative (+)-1 was also prepared from compound 3.In this synthe
- Roberts, Stanley M.,Shoberu, Karoline A.
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p. 2625 - 2632
(2007/10/02)
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- N-ACYLAMINO ACID DERIVATIVES AND THEIR PHARMACEUTICAL COMPOSITIONS
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An N-acylamino acid derivative of the formula: STR1 wherein the substituents are herein defined or a salt thereof, which is useful as hypotensive drugs.
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