3181-38-2Relevant articles and documents
Synthesis of isotopically labelled versions of adenosine agonist GR79236
Wadsworth, Alan H.,Newman, John J.,Wipperman, Mark D.,Fellows, Ian,Sutherland, Derek R.
, p. 11 - 28 (2000)
Versions of adenosine receptor agonist GR79236, labelled either with carbon-14 at C-8 of the purine ring or with tritium in the cyclopentyl ring, were prepared in overall yields of 64% and 25% respectively. A mass labelled [M + 4] version containing carbon-13, nitrogen-15, and deuterium was also prepared in 3% yield.
The "speedy" Synthesis of Atom-Specific 15N Imino/Amido-Labeled RNA
Neuner, Sandro,Santner, Tobias,Kreutz, Christoph,Micura, Ronald
, p. 11634 - 11643 (2015)
Although numerous reports on the synthesis of atom-specific 15N-labeled nucleosides exist, fast and facile access to the corresponding phosphoramidites for RNA solid-phase synthesis is still lacking. This situation represents a severe bottleneck for NMR spectroscopic investigations on functional RNAs. Here, we present optimized procedures to speed up the synthesis of 15N(1) adenosine and 15N(1) guanosine amidites, which are the much needed counterparts of the more straightforward-to-achieve 15N(3) uridine and 15N(3) cytidine amidites in order to tap full potential of 1H/15N/15N-COSY experiments for directly monitoring individual Watson-Crick base pairs in RNA. Demonstrated for two preQ1 riboswitch systems, we exemplify a versatile concept for individual base-pair labeling in the analysis of conformationally flexible RNAs when competing structures and conformational dynamics are encountered.
SAICAR Synthesis method
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Paragraph 0053-0056; 0076-0078; 0098-0100, (2021/11/06)
A method of synthesizing SAICAR of the present invention is carried out at 5 - amino -1 - ((). 2R. 3R. 4S. 5R-3, 4 -dihydroxy -5 - (hydroxymethyl) tetrahydrofuran -2 -yl) -1H- Imidazol -4 - formamide is the starting material and is sequentially subjected to 5 - amino -1 - ((). 3aR. 4R. 6R. 6aR) -6 - (Hydroxymethyl) -2, 2 -dimethyltetrahydrofuran [3,4 -]d] [1, 3] Diox -4 - group) -1H-imidazole -4 -carboxamide. 5 - Amino -1 - (()3aR. 4R. 6R. 6aR) -6 - (Hydroxymethyl) -2, 2 -dimethyltetrahydrofuran [3,4 -]d] [1, 3] Diox -4 - group) -1H- Imidazole -4 - carboxylic acid, dibenzyl (5 - amino -1 -) (()3aR. 4R. 6R. 6aR) -6 - (Hydroxymethyl) -2, 2 -dimethyltetrahydrofuran [3,4 -]d] [1, 3] Diox -4 - group) -1H- Imidazol -4 - carbonyl) . LOf - aspartic acid and the like to obtain a finished product purity of up to 99.6%, impurities 0.4%, diastereomeric excess (de) values 97.3% and a yield 16.9%.
Crystal form, preparation method and purpose of triacetyl-3-hydroxyphenyl adenosine
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Paragraph 0006; 0036-0037, (2021/06/22)
The invention relates to a crystal form, a preparation method and a purpose of hyperlipemia-treating medicine of triacetyl-3-hydroxyphenyl adenosine. The crystal form of the triacetyl-3-hydroxyphenyl adenosine comprises a type I crystal and a type II crystal of 2',3',5'-tri-O-acetyl-N6-(3-hydroxyphenyl) adenosine with a blood-lipid regulating effect, wherein the type I crystal has an X-ray powder diffraction pattern as shown in Figure 1, and the type II crystal has an X-ray powder diffraction pattern as shown in Figure 4.
The isoprenoid derivative N6-benzyladenosine CM223 exerts antitumor effects in glioma patient-derived primary cells through the mevalonate pathway
Ciaglia, Elena,Grimaldi, Manuela,Abate, Mario,Scrima, Mario,Rodriquez, Manuela,Laezza, Chiara,Ranieri, Roberta,Pisanti, Simona,Ciuffreda, Pierangela,Manera, Clementina,Gazzerro, Patrizia,D'Ursi, Anna Maria,Bifulco, Maurizio
supporting information, p. 2287 - 2301 (2017/06/28)
Background and Purpose: N6-Isopentenyladenosine (i6A) is a modified nucleoside exerting in vitro and in vivo antiproliferative effects. We previously demonstrated that the actions of i6A correlate with the expression and activity of farnesyl pyrophosphate synthase (FPPS), a key enzyme involved in the mevalonate (MVA) pathway, which is aberrant in brain cancer. To develop new anti-glioma strategies, we tested related compounds exhibiting greater activity than i6A. Experimental Approach: We designed and synthesized i6A derivatives characterized by the introduction of diverse chemical moieties in the N6 position of adenosine and tested for their efficacy in U87 cells and in primary glioma cultures, derived from patients. NMR-based structural analysis, molecular docking calculations and siRNA mediated knockdown were used to clarify the molecular basis of their action, targeting FPPS protein. Key Results: CM223, the i6A derivative including a benzyl moiety in N6 position of adenine, showed marked activity in selectively targeting glioma cells, but not normal human astrocytes. This was due to induction of intrinsic pathways of apoptosis and inhibition of proliferation, along with blockade of FPPS-dependent protein prenylation, which counteracted oncogenic signalling mediated by EGF receptors. Conclusion and Implications: The biological effects together with structural data on interaction of CM223 with FPPS, provided additional evidence for the correlation of the i6A/CM223 antitumor activity with FPPS modulation. Because the MVA pathway is an important promising target, CM223 and its derivatives should be considered interesting active molecules in antiglioma research.
A process for preparing natural nucleoside powder clitocybin method
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Paragraph 0021; 0025-0027, (2017/10/26)
The invention discloses a new method for preparing natural nucleoside nebularine. According to the method disclosed by the invention, cheap inosine is used as a raw material and is subjected to three reactions including acyl protection, sulfuration and desulfuration to finally obtain the target product nebularine; in the desulfuration step, since 50% nitric acid is used as a desulfuration agent, such reaction conditions easily causing explosion as diazotization in the conventional synthesis method can be avoided, no heavy metal catalyst is used, no column chromatography is needed in the whole process, large-scale synthesis can be realized easily; and moreover, the new method for preparing natural nucleoside nebularine is suitable for research on medicine activity and further large-scale preparation.
Selective Acylation of Nucleosides, Nucleotides, and Glycerol-3-phosphocholine in Water
Fernández-García, Christian,Powner, Matthew W.
supporting information, p. 78 - 83 (2016/12/26)
A convenient selective synthesis of 2′,3′-di-O-acetyl-nucleotide-5′-phosphates, 2′,3′-di-O-acetyl-nucleotide-5′-triphosphates and 2′,3′,5′-tri-O-acetyl-nucleosides in water has been developed. Furthermore, a long-chain selective glycerol-3-phosphocholine diacylation is elucidated. These reactions are environmentally benign, rapid, high yielding, and the products are readily purified. Importantly, this reaction may indicate a prebiotically plausible reaction pathway for the selective acylation of key metabolites to facilitate their incorporation into protometabolism.
α,β-Methylene-ADP (AOPCP) Derivatives and Analogues: Development of Potent and Selective ecto-5′-Nucleotidase (CD73) Inhibitors
Bhattarai, Sanjay,Freundlieb, Marianne,Pippel, Jan,Meyer, Anne,Abdelrahman, Aliaa,Fiene, Amelie,Lee, Sang-Yong,Zimmermann, Herbert,Yegutkin, Gennady G.,Str?ter, Norbert,El-Tayeb, Ali,Müller, Christa E.
supporting information, p. 6248 - 6263 (2015/08/24)
ecto-5′-Nucleotidase (eN, CD73) catalyzes the hydrolysis of extracellular AMP to adenosine. eN inhibitors have potential for use as cancer therapeutics. The eN inhibitor α,β-methylene-ADP (AOPCP, adenosine-5′-O-[(phosphonomethyl)phosphonic acid]) was used as a lead structure, and derivatives modified in various positions were prepared. Products were tested at rat recombinant eN. 6-(Ar)alkylamino substitution led to the largest improvement in potency. N6-Monosubstitution was superior to symmetrical N6,N6-disubstitution. The most potent inhibitors were N6-(4-chlorobenzyl)- (10l, PSB-12441, Ki 7.23 nM), N6-phenylethyl- (10h, PSB-12425, Ki 8.04 nM), and N6-benzyl-adenosine-5′-O-[(phosphonomethyl)phosphonic acid] (10g, PSB-12379, Ki 9.03 nM). Replacement of the 6-NH group in 10g by O (10q, PSB-12431) or S (10r, PSB-12553) yielded equally potent inhibitors (10q, 9.20 nM; 10r, 9.50 nM). Selected compounds investigated at the human enzyme did not show species differences; they displayed high selectivity versus other ecto-nucleotidases and ADP-activated P2Y receptors. Moreover, high metabolic stability was observed. These compounds represent the most potent eN inhibitors described to date.
Tosvinyl and besvinyl as protecting groups of imides, azinones, nucleosides, sultams, and lactams. Catalytic conjugate additions to tosylacetylene
Petit, Elena,Bosch, Llus,Font, Joan,Mola, Laura,Costa, Anna M.,Vilarrasa, Jaume
, p. 8826 - 8834 (2015/01/08)
The use of the 2-(4-methylphenylsulfonyl)-ethenyl (tosvinyl, Tsv) group for the protection of the NH group of a series of imides, azinones (including AZT), inosines, and cyclic sulfonamides has been examined. The Tsvprotected derivatives are obtained in excellent yields by conjugate addition to tosylacetylene (ethynyl p-tolyl sulfone). The stereochemistry of the double bond can be controlled at will: with only 1 mol % of Et3N or with catalytic amounts of NaH, the Z stereoisomers are generated almost exclusively, while the E isomers are obtained using a stoichiometric amount of DMAP. Analogous phenylsulfonylvinyl-protected groups (with the besvinyl or Bsv group instead of Tsv) are obtained stereospecifically by reaction with (Z)- or (E)-bis(phenylsulfonyl)ethene. For lactams and oxazolidinones, this last method is much better. The Tsv and Bsv groups are stable in the presence of non-nucleophilic bases and to acids. They can be removed highly effectively via a conjugate addition-elimination mechanism using pyrrolidine or sodium dodecanethiolate as nucleophiles.
Nucleophile-catalyzed additions to activated triple bonds. protection of lactams, imides, and nucleosides with MocVinyl and related groups
Mola, Laura,Font, Joan,Bosch, Lluis,Caner, Joaquim,Costa, Anna M.,Etxebarria-Jardi, Gorka,Pineda, Oriol,De Vicente, David,Vilarrasa, Jaume
, p. 5832 - 5842 (2013/07/26)
Additions of lactams, imides, (S)-4-benzyl-1,3-oxazolidin-2-one, 2-pyridone, pyrimidine-2,4-diones (AZT derivatives), or inosines to the electron-deficient triple bonds of methyl propynoate, tert-butyl propynoate, 3-butyn-2-one, N-propynoylmorpholine, or
