73340-78-0Relevant academic research and scientific papers
Formation and propagation of well-defined Pd nanoparticles (PdNPs) during C-H bond functionalization of heteroarenes: Are nanoparticles a moribund form of Pd or an active catalytic species?
Baumann, Christoph G.,De Ornellas, Sara,Reeds, Jonathan P.,Storr, Thomas E.,Williams, Thomas J.,Fairlamb, Ian J.S.
, p. 6174 - 6187 (2015/04/14)
Abstract Examination of a series of C-H bond functionalization reactions of heteroarenes (e.g., indole, benzoxazole, benzthiazole, benzimidazole and purine derivatives) mediated by Pd(OAc), a commonly used C-H bond functionalization catalyst, reveals that well-defined Pd nanoparticles (PdNPs) are rapidly formed under working catalyst conditions. The PdNPs can be characterized ex situ after entrapment in a polymer matrix (polyvinylpyrrolidinone, PVP). Independently synthesized Pd(PVP)NPs are catalytically competent species, exhibiting catalyst activity commensurate with Pd(OAc) in several C-H bond functionalization reactions. Across a range of reactions, Pd concentration is a common variable, which can be linked to the propagation of PdNPs under working catalytic conditions using polar solvents like DMF, DMSO and acetic acid.
Structure-activity relationship of adenosine 5′-diphosphoribose at the transient receptor potential melastatin 2 (TRPM2) channel: Rational design of antagonists
Moreau, Christelle,Kirchberger, Tanja,Swarbrick, Joanna M.,Bartlett, Stephen J.,Fliegert, Ralf,Yorgan, Timur,Bauche, Andreas,Harneit, Angelika,Guse, Andreas H.,Potter, Barry V. L.
, p. 10079 - 10102 (2014/01/17)
Adenosine 5′-diphosphoribose (ADPR) activates TRPM2, a Ca 2+, Na+, and K+ permeable cation channel. Activation is induced by ADPR binding to the cytosolic C-terminal NudT9-homology domain. To generate the first structure-activity relationship, systematically modified ADPR analogues were designed, synthesized, and evaluated as antagonists using patch-clamp experiments in HEK293 cells overexpressing human TRPM2. Compounds with a purine C8 substituent show antagonist activity, and an 8-phenyl substitution (8-Ph-ADPR, 5) is very effective. Modification of the terminal ribose results in a weak antagonist, whereas its removal abolishes activity. An antagonist based upon a hybrid structure, 8-phenyl-2′-deoxy-ADPR (86, IC50 = 3 μM), is more potent than 8-Ph-ADPR (5). Initial bioisosteric replacement of the pyrophosphate linkage abolishes activity, but replacement of the pyrophosphate and the terminal ribose by a sulfamate-based group leads to a weak antagonist, a lead to more drug-like analogues. 8-Ph-ADPR (5) inhibits Ca2+ signalling and chemotaxis in human neutrophils, illustrating the potential for pharmacological intervention at TRPM2.
Two-step synthesis of novel, bioactive derivatives of the ubiquitous cofactor nicotinamide adenine dinucleotide (NAD)
Pesnot, Thomas,Kempter, Julia,Schemies, J?rg,Pergolizzi, Giulia,Uciechowska, Urszula,Rumpf, Tobias,Sippl, Wolfgang,Jung, Manfred,Wagner, Gerd K.
supporting information; experimental part, p. 3492 - 3499 (2011/07/30)
We report the design and concise synthesis, in two steps from commercially available material, of novel, bioactive derivatives of the enzyme cofactor nicotinamide adenine dinucleotide (NAD). The new synthetic dinucleotides act as sirtuin (SIRT) inhibitors and show isoform selectivity for SIRT2 over SIRT1. An NMR-based conformational analysis suggests that the conformational preferences of individual analogues may contribute to their isoform selectivity.
8-(p-CF3-cinnamyl)-modified purine nucleosides as promising fluorescent probes
Zilbershtein, Lital,Silberman, Alon,Fischer, Bilha
experimental part, p. 7763 - 7773 (2011/12/14)
Natural nucleotides are not useful as fluorescent probes because of their low quantum yields. Therefore, a common methodology for the detection of RNA and DNA is the application of extrinsic fluorescent dyes coupled to bases in oligonucleotides. To overco
New insights into the design of inhibitors of human S-adenosylmethionine decarboxylase: studies of adenine C8 substitution in structural analogues of S-adenosylmethionine
McCloskey, Diane E.,Bale, Shridhar,Secrist III, John A.,Tiwari, Anita,Moss III, Thomas H.,Valiyaveettil, Jacob,Brooks, Wesley H.,Guida, Wayne C.,Pegg, Anthony E.,Ealick, Steven E.
scheme or table, p. 1388 - 1407 (2009/12/07)
S-Adenosylmethionine decarboxylase (AdoMetDC) is a critical enzyme in the polyamine biosynthetic pathway and depends on a pyruvoyl group for the decarboxylation process. The crystal structures of the enzyme with various inhibitors at the active site have shown that the adenine base of the ligands adopts an unusual syn conformation when bound to the enzyme. To determine whether compounds that favor the syn conformation in solution would be more potent AdoMetDC inhibitors, several series of AdoMet substrate analogues with a variety of substituents at the 8-position of adenine were synthesized and analyzed for their ability to inhibit hAdoMetDC. The biochemical analysis indicated that an 8-methyl substituent resulted in more potent inhibitors, yet most other 8-substitutions provided no benefit over the parent compound. To understand these results, we used computational modeling and X-ray crystallography to study C8-substituted adenine analogues bound in the active site.
Site-selective direct arylation of unprotected adenine nucleosides mediated by palladium and copper: insights into the reaction mechanism
Storr, Thomas E.,Firth, Andrew G.,Wilson, Karen,Darley, Kate,Baumann, Christoph G.,Fairlamb, Ian J.S.
, p. 6125 - 6137 (2008/09/21)
Reaction conditions facilitating the site-selective direct aryl functionalisation at the C-8 position of adenine nucleosides have been identified. Many different aromatic components may be effectively cross-coupled to provide a diverse array of arylated adenine nucleoside products without the need for ribose or adenine protecting groups. The optimal palladium catalyst loading lies between 0.5 and 5 mol %. Addition of excess mercury to the reaction had a negligible affect on catalysis, suggesting the involvement of a homogeneous catalytic species. A study by transmission electron microscopy (TEM) shows that metal containing nanoparticles, ca. 3 nm with good uniformity, are formed during the latter stages of the reaction. Stabilised PVP palladium colloids (PVP=N-polyvinylpyrrolidone) are catalytically active in the direct arylation process, releasing homogenous palladium into solution. The effect of various substituted 2-pyridine ligand additives has been investigated. A mechanism for the site-selective arylation of adenosine is proposed.
Suzuki-Miyaura cross-coupling of unprotected halopurine nucleosides in water - Influence of catalyst and cosolvent
Collier, Alice,Wagner, Gerd K.
, p. 3713 - 3721 (2007/10/03)
Reaction conditions for the Suzuki-Miyaura cross-coupling of unprotected halopurine nucleosides with arylboronic acids in aqueous media were investigated. A series of arylated purine nucleosides was prepared in water without an organic cosolvent, using either Pd(PPh3)4 or Pd(OAc)2/TPPTS as the catalyst. Copyright Taylor & Francis Group, LLC.
PURINE NUCLEOTIDE DERIVATIVES
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Page/Page column 21; 56, (2010/02/15)
This invention provides novel 8-carbyl substituted cAMPS and a novel procedures for the preparation of 8-Br-cAMP, a key starting material.
Synthesis of novel 2-aryl AICAR derivatives
Kohyama, Naoki,Katashima, Tomoyuki,Yamamoto, Yukio
, p. 2799 - 2804 (2007/10/03)
Novel 2-aryl AICAR (5-Amino-1-β-D-ribofuranosylimidazole-4- carboxamide) derivatives 8 were synthesized via the Suzuki-Miyaura cross-coupling reactions of 8-bromoadenosine. Following conversion of the adenine moiety of 4 to hypoxanthine (5) and the introduction of a MEM group, hydrolysis of 7 gave desired 2-aryl AICAR derivatives 8.
Efficient one-step Suzuki arylation of unprotected halonucleosides, using water-soluble palladium catalysts
Western, Elizabeth C.,Daft, Jonathan R.,Johnson II, Edward M.,Gannett, Peter M.,Shaughnessy, Kevin H.
, p. 6767 - 6774 (2007/10/03)
Modification of nucleosides to give pharmaceutically active compounds, mutagenesis models, and oligonucleotide structural probes continues to be of great interest. The aqueous-phase modification of unprotected halonucleosides is reported herein. Using a catalyst derived from tris(3-sulfonatophenyl)phosphine (TPPTS) and palladium acetate, 8-bromo-2′-deoxyguanosine (8-BrdG) is coupled with arylboronic acids to give 8-aryl-2′-deoxyguanosine adducts (8-ArdG) in excellent yield in a 2: 1 water: acetonitrile solvent mixture. The TPPTS ligand was found to be superior to water-soluble alkylphosphines for this coupling reaction. The coupling chemistry has been extended to 8-bromo-2′-deoxyadenosine (8-BrdA) and 5-iodo-2′-deoxyuridine (5-IdU), as well as the ribonucleosides 8-bromoguanosine and 8-bromoadenosine. Good to excellent yields of arylated adducts are obtained in all cases. With use of tri(4,6-dimethyl-3-sulfonatophenyl)phosphine (TXPTS), the Suzuki coupling of 8-BrdA and 5-IdU can be accomplished in less than 1 h at room temperature. This methodology represents an efficient and general method for halonucleoside arylation that does not require prior protection of the nucleoside.
