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1.
Kazuo Kamaike Mitsuhisa Isobe Yoshihiro Kayama Etsuko Kawashima 《Nucleosides, nucleotides & nucleic acids》2013,32(1):29-35
Nucleophilic aromatic substitution of 9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-6-chloro-2-fluoro-9 H-purine with N-(tert-butyldimethylsilyl)[ 15 N]phthalimide in the presence of a catalytic amount of CsF at room temperature in DMF efficiently afforded the 6-chloro-2-[ 15 N]phthalimidopurine derivative, which was subsequently converted to the [2-15N]guanosine derivative was also efficiently synthesized through a similar procedure. 相似文献
2.
《Nucleosides, nucleotides & nucleic acids》2013,32(1-2):59-75
The nucleophilic addition–elimination reaction of 2′,3′,5′-tri-O-acetyl-2-fluoro-O 6-[2-(4-nitrophenyl)ethyl]inosine (8) with [15N]benzylamine in the presence of triethylamine afforded the N 2-benzyl[2-15N]guanosine derivative (13) in a high yield, which was further converted into the N 2-benzoyl[2-15N] guanosine derivative by treatment with ruthenium trichloride and tetrabutyl-ammonium periodate. A similar sequence of reactions of 2′,3′,5′-tri-O-acetyl-2-fluoro-O 6-[2-(methylthio)ethyl]inosine (9) and the 6-chloro-2-fluoro-9-(β-D-ribofuranosyl)-9H-purine derivative (11), which were respectively prepared from guanosine, with potassium [15N]phthalimide afforded the N 2-phthaloyl [2-15N]guanosine derivative (15; 62%) and 9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-6-chloro-2-[15N]phthalimido-9H-purine (17; 64%), respectively. Compounds 15 and 17 were then efficiently converted into 2′,3′,5′-tri-O-acetyl[2-15N]guanosine. The corresponding 2′-deoxy derivatives (16 and 18) were also synthesized through similar procedures. 相似文献
3.
Robert A. Harris 《Archives of biochemistry and biophysics》1975,169(1):168-180
Fatty acid synthesis by isolated liver cells is dependent upon the availability of lactate and pyruvate. A lag in fatty acid synthesis is explained by time being required for lactate and pyruvate to accumulate to maximum concentrations in the incubation medium. The initial rate of fatty acid synthesis is not linear with cell concentration, being disproportionately greater at higher cell concentrations because optimal lactate and pyruvate concentrations are established in the medium more rapidly. The accumulation of lactate and pyruvate is inhibited markedly by N6,O2′-dibutyryl adenosine 3′,5′-monophosphate. This accounts in part for the inhibition of fatty acid synthesis caused by this cyclic nucleotide. Other sites of action are apparent, however, because exogenous lactate plus pyruvate only partially relieves the inhibition. The profile of metabolic intermediates suggests that N6,O2′-dibutyryl adenosine 3′,5′-monophosphate inhibits the conversion of glycogen to pyruvate and lactate by decreasing the effectiveness of phosphofructokinase and pyruvate kinase. 相似文献
4.
Lydmila D. Garaeva Irina V. Yartseva Stalina Ya. Melnik 《Nucleosides, nucleotides & nucleic acids》2013,32(6):1295-1303
Abstract A synthesis of 4,6-dimethylthio-1-(2-deoxy-β-D-erythro-pentofuranosyl)pyrazolo[3,4-d]pyrimidine-3-carbonitrile (4) is described using the stereospecific sodium salt glycosylation procedure. Condensation of the sodium salt of 4,6-dimethylthiopyrazolo[3,4-d]pyrimidine-3-carbonitrile (1) with 1-chloro-2-deoxy-3,5-di-O-p-toluoyl-α-D-eythro-pentofuranose (2) gave exclusively the corresponding blocked nucleoside (3) with β-anomeric configuration, which on deprotection provided 2′-deoxyriboside 4. Aglycone functional groups transformations of 4 led to related 3,4,6-trisubstituted pyrazolo[3,4-d]pyrimidine-2′-deoxynucleosides. These compounds are devoid of any significant cytotoxic activity in vitro. 相似文献
5.
This paper describes a [15N,1H]/[13C,1H]-TROSY experiment for the simultaneous acquisition of the heteronuclear chemical shift correlations of backbone amide 15N–1H groups, side chain 15N–1H2 groups and aromatic 13C–1H groups in otherwise highly deuterated proteins. The 15N–1H and 13C–1H correlations are extracted from two subspectra of the same data set, thus preventing possible spectral overlap of aromatic and amide protons in the 1H dimension. The side-chain 15N–1H2 groups, which are suppressed in conventional [15N,1H)-TROSY, are observed with high sensitivity in the 15N–1H subspectrum. [15N,1H]/[13C,1H]-TROSY was used as the heteronuclear correlation block in a 3D [1H,1H]-NOESY-[15N,1H]/[13C,1H]-TROSY experiment with the membrane protein OmpA reconstituted in detergent micelles of molecular weight 80000 Da, which enabled the detection of numerous NOEs between backbone amide protons and both aromatic protons and side chain 15N–1H2 groups. 相似文献
6.
《Nucleosides, nucleotides & nucleic acids》2013,32(5-8):1657-1659
Abstract 2′-2H- and 3′-2H-CDP were synthesized from 5′-MMT-3′-O-TBDMS and 2′,5′- O-diTBDMS cytidine derivatives, respectively, by oxidation followed by acidic removal of 5′-protection, reduction with [NaBD(OAc)3] and finally displacement of a tosyl group by pyrophosphate. 相似文献
7.
Tetsuo Kato Takeshi Endo Jirbreveí Zbreveemlicbreveka 《Nucleosides, nucleotides & nucleic acids》2013,32(1):81-87
Abstract Bromination of the title compound 1 with bromine in phosphate buffer has led to 8-bromo-N6, N6-dimethyl-2′,3′-0-isopropylidene-adenosine (2) and 2′,3′-0-isopropylidene-N6-methyladenosine (3). Under similar conditions, compound 2 gave 8-bromo-2′,3′-0-isopropylidene-N6-methyladenosine (4). The transformations 1 → 3 and 2 → 4 represent biomimetic models of in vivo N6-demethylation of antibiotic puromycin. 相似文献
8.
Yoshihiko Shinohara Hiroshi Hasegawa Tomoyoshi Kaneko Yuka Tamura Takao Hashimoto Kimiyoshi Ichida 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2010,878(3-4):417-422
Homocysteine plays a key role in several pathophysiological conditions. To assess the methionine–homocysteine kinetics by stable isotope methodology, we developed a simultaneous quantification method of [2H7]methionine, [2H4]methionine, methionine, [2H4]homocysteine and homocysteine in rat plasma by gas chromatography–mass spectrometry (GC–MS). [13C]Methionine and [13C]homocysteine were used as analytical internal standards to account for losses associated with the extraction, derivatization and chromatography. For labeled and non-labeled homocysteine measurements, disulfide bonds between homocysteine and other thiols or proteins were reduced by dithiothreitol. The reduced homocysteine and methionine species were purified by cation-exchange chromatography and derivatized with isobutyl chlorocarbonate in water–ethanol–pyridine. Quantification was carried out by selected ion monitoring of the molecular-related ions of N(O,S)-isobutyloxycarbonyl ethyl ester derivatives on the chemical ionization mode. The intra- and inter-day precision of the assay was less than 6% for all labeled and non-labeled methionine and homocysteine species. The method is sensitive enough to determine pharmacokinetics of labeled methionine and homocysteine. 相似文献
9.
James Cook F. Christopher Zusi Matthew D. Hill Haiquan Fang Bradley Pearce Hyunsoo Park Lizbeth Gallagher Ivar M. McDonald Linda Bristow John E. Macor Richard E. Olson 《Bioorganic & medicinal chemistry letters》2017,27(22):5002-5005
We describe an efficient and convergent synthesis of a series of (1′S,2R,4′S)-3H-4′-azaspiro[benzo[4,5]imidazo[2,1-b]oxazole-2,2′-bicyclo[2.2.2]octanes] displaying potency for the α7 nicotinic acetylcholine receptor (nAChR) and good selectivity vs. the related 5-HT3A receptor. 相似文献
10.
Maqbool A. Siddiqui Harry Ford Jr. Clifford George Victor E. Marquez 《Nucleosides, nucleotides & nucleic acids》2013,32(1-3):235-250
Abstract A new chiral synthesis of the pseudosugar synthon (1R,2S,4R,5S)-1-[(benzyloxy)methyl]-2-tert-butyloxy-4-hydroxybicyclo[3.1.0]hexane (12) is reported. This compound was used as a template for the construction of carbocyclic nucleoside 4, a conformationally rigid analogue of 2′-deoxyaristeromycin. The X-ray structure and 1H NMR analysis confirmed the exclusive North [2′-exo (2E)] conformation of 4 which is vastly different from that of other non-rigid carbocyclic nucleosides. Compound 4 showed good in vitro antiviral activity against human cytomegalovirus and EBV with minimal cytotoxicity. 相似文献
11.
《Nucleosides, nucleotides & nucleic acids》2013,32(5-7):911-914
The coupling of 4-aminopyrazolo [3, 4-d]pyrimidine with the appropriate thio sugar gave a 3:1 ratio of α,β blocked 4-amino-1-(2-deoxy-4-thio-D-erythropentofuranosyl)- 1H pyrazolo[3,4-d]pyrimidine nucleosides. The mixture was deblocked, both the anomers were separated, and the β-anomer was readily deaminated by adenosine deaminase. The nucleosides have been characterized, and their anomeric configurations have been determined by proton NMR. All three nucleosides were evaluated against a panel of human tumor cell lines for cytotoxicity in vitro. The details of a convenient and high yielding synthesis of these nucleosides are described. 相似文献
12.
John A. Walker II Jiong J. Chen Jack M. Hinkley Dean S. Wise Leroy B. Townsend 《Nucleosides, nucleotides & nucleic acids》2013,32(10-11):1999-2012
Abstract The palladium-catalyzed cross-couplings of 2-chloro-3,5-diamino-6-iodopyrazine (1a) and methyl 3-amino-6-iodopyrazine-2-carboxylate (1b) with 1,4-anhydro-3,5-O-bis[(tert-butyl)dimethylsilyl]-2-deoxy-D-erythro-pent-1-enitol (2) followed by desilylation and stereospecific reduction of the 2′-deoxy-3′-keto adduct leads to the formation of 2-chloro-6-(2-deoxy-ß-D-ribofuranosyl)-3,5-diaminopyrazine (4a) and methyl 3-amino-6-(2-deoxy-ß-D-ribofuranosyl)pyrazine-2-carboxylate (4b) in 58% yield and 21% yield, respectively. These are the first syntheses of the heretofore unknown 2′-deoxy pyrazine C-nucleosides and demonstrate the utility of a convergent approach for the synthesis of pyrazine C-nucleosides. 相似文献
13.
Miroslav Bobek Pittaya Tuntiwachwuttikul M. Mohsen Ismail Thomas J. Bardos 《Nucleosides, nucleotides & nucleic acids》2013,32(8):1657-1665
Abstract N-Aminopyrazine analogues of cytidine and 2′-deoxycytidine were prepared from 1-(β-D-ribofuranosyl)-1,2-dihydro-2-oxopyrazine and 1-(2-deoxy-β-D-ribofuranosyl)-1,2-dihydro-2-oxopyrazine, respectively, by amination with O-mesitylenesulfonylhydroxylamine. 相似文献
14.
Etsuko Kawashima Takeshi Sekine Kaoru Umabe Yuhki Naito Kazuo Kamaike Chojiro Kojima 《Nucleosides, nucleotides & nucleic acids》2013,32(6-7):1597-1598
Abstract In addition to the synthesis of 2′-deoxy[5′-13C]ribonucleosides (6) via the D-[5-13C]ribose derivative (4), the construction of the corresponding dodecanucleotide with the Dickerson's sequence and its HMQC-NOESY NMR analysis are described. 相似文献
15.
Abstract New pyrrolo[3,2-c]pyridine nucleosides (e.g. 2, 2, 4) have been prepared via solid-1iquid phase-transfer glycosylation. Additionally, building blocks for oligonucleotide synthesis are described. 相似文献
16.
Won Jun Choi Hyuk Woo Lee Hea Ok Kim Moshe Chinn Zhan-Guo Gao Amit Patel Kenneth A. Jacobson Hyung Ryong Moon Young Hoon Jung Lak Shin Jeong 《Bioorganic & medicinal chemistry》2009,17(23):8003-8011
On the basis of a bioisosteric rationale, 4′-thionucleoside analogues of IB-MECA (N6-(3-Iodo-benzyl)-9-(5′-methylaminocarbonyl-β-d-ribofuranosyl)adenine), which is a potent and selective A3 adenosine receptor (AR) agonist, were synthesized from d-gulonic acid γ-lactone. The 4′-thio analogue (5h) of IB-MECA showed extremely high binding affinity (Ki = 0.25 nM) at the human A3AR and was more potent than IB-MECA (Ki = 1.4 nM). Bulky substituents at the 5′-uronamide position, such as cyclohexyl and 2-methylbenzyl, in this series of 2-H nucleoside derivatives were tolerated in A3AR binding, although small alkyl analogues were more potent. 相似文献
17.
Zhanni Gu Lingyan Wu Yanan Duan Jiang Wang Shengbin Zhou Jingya Li Kaixian Chen Jia Li Hong Liu 《Bioorganic & medicinal chemistry》2018,26(8):2017-2027
To discover more derivatives with better glucose-lowering efficacy compared with berberine, twenty-three novel compounds with 4,7,12,12a-tetrahydro-5H-thieno[3′,2′:3,4]pyrido[1,2-b]isoquinoline or 5,8,12,12a-tetrahydro-6H-thieno[2′,3′:4,5]pyrido[2,1-a]isoquinoline cores were designed, synthesized, and biologically evaluated in vitro in continuation of our previous work on indirect activators of adenosine 5′-monophosphate-activated protein kinase (AMPK). Nine compounds effectively stimulated glucose consumption (>2.3-fold at 10 μM) in L6 myotube cells, and two compounds (4d and 4s) exhibited superior inhibitory activity (<57.6% at 5 μM) compared with berberine on gluconeogenesis in rat primary hepatocytes. Additionally, these compounds significantly up-regulated the phosphorylation of AMPK and its substrate, acetyl-CoA carboxylase (ACC) and slightly decreased the mitochondrial membrane potential in L6 myotube cells. 相似文献
18.
《International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology》1988,15(6):651-657
Intravenous injection of the gallium chelating agents, N,N′-ethylene bis[2-hydroxy-5-carboxyphenylglycine], (COOH-EHPG), or desferrioxamine (DFO) after gallium-67 (67Ga) injection, improved tumour/non-tumour tissue uptake ratios in mice bearing the EMT-6 sarcoma. Six hours post injection of gallium and 2 h post chelator, COOH-EHPG enhanced the tumour/blood ratios by an order of magnitude compared to untreated controls, whereas DFO increased the ratios three-fold. Twenty two hours post gallium and 2 h post chelator, the increases in ratios compared to controls were seven-fold for COOH-EHPG and two-fold for DFO. The study thus demonstrated the superior ability of COOH-EHPG for the enhancement of 67Ga tumour/blood ratios compared with DFO. 相似文献
19.
Abstract The syntheses of 1-(2-deoxy-β-D-erythro-pentofuranosyl)-4,5,7,8-tetrahydro-6H-imidazo[4,5-e] [1,4]diazepine-5,8-dione (9β), its 3-glycosyl regioisomer (16β), and their respective α anomers (9α and 16α), are reported. Conformational and configurational studies, employing 1H NMR NOE and CD spectroscopy, are described. The single-crystal X-ray structural analysis of 9β is presented. The attempted enzymic glycosylation of the heterocyclic base 6 with a bacterial purine nucleoside phosphorylase was not successful. 相似文献
20.
Whi-Gun Chae 《Biotechnology and Bioprocess Engineering》1999,4(1):17-20
Facile synthetic methods of 2′,5′-dideoxy-, 2′,3′-dideoxy- and 3′-deoxy-1,N
6-ethenoadenosine nucleosides by either an enzymatic dideoxyribosyl transfer reaction or a simple chemical reaction were proposed.
The synthetic products were isolated and purified by preparative HPLC and their structures were confirmed by1H NMR (500 MHz) and FAB-MS including high resolution mass measurement. These modified nucleoside analogs have not been reported
yet. Therefore, these modified nucleoside analogs are of potential value to be studied further for biological activity such
as anticancer or antiviral. 相似文献