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1.
《Nucleosides, nucleotides & nucleic acids》2013,32(5-7):577-580
Starting from 2-C-methyl-ribonolactone, 1,2,3,5-tetra-O-acetyl-2-C-methyl-4-thioribofuranose was synthesized and condensed with heterocyclic bases to afford 2′-C-methyl-4′-thioribonucleosides. 相似文献
2.
Nathalie Richard Horacio Salomon Maureen Oliveira Robert Rando Mark A. Wainberg 《Nucleosides, nucleotides & nucleic acids》2013,32(4-5):773-778
Abstract Resistant variants were selected in vitro against two novel nucleoside analogues, (+) dOTC and (-) dOTFC using the HIV-1 molecular clone HXB2D. The variants obtained displayed 6.5-fold and 10-fold resistance to these compounds, respectively. Cloning and sequencing of the RT genes of the selected viruses identified two mutations, M184I for (+) dOTC and M184V for (-) dOTFC. Results with mutated recombinant clones of HXB2D confirmed the importance of these mutations in MT-4 cells. The resistance profiles of clinical samples with wild-type or 3TC-resistant phenotypes were also studied; low to moderate levels of cross-resistance were observed against the novel compounds. 相似文献
3.
Jean M. J. Tronchet Mohammed Iznaden Françoise Barbalat-Rey Istvan Komaromi Naz Dolatshahi Gérald Bernardinelli 《Nucleosides, nucleotides & nucleic acids》2013,32(8):1737-1758
Abstract A series of 3′-branched 4′-azanucleoside analogues have been prepared. These compounds comprise three asymmetric atoms, two carbons and one nitrogen. They constitute nucleoside analogues imparted with a “flickering configuration”, the nitrogen inversion replacing a D-L epimerization of their natural congeners. The 1′,3′-cis and 1′,3′-trans isomers have been separated and their configuration established by 1H NMR and the X-ray diffraction structure of one crystalline example. The configurations of the frozen invertomers were assessed by low temperature 1H NMR experiments assisted by molecular mechanics simulations. None of these compounds exhibited any significant in vitro antiviral activity. 相似文献
4.
J. Allen Miller Ashley W. Pugh G. Mustafa Ullah 《Nucleosides, nucleotides & nucleic acids》2013,32(9):1475-1486
Abstract 2,2′-Anhydro-4′-thio-β-and α-nucleosides 9 and 10 have been prepared by an in situ 4-thio-1,2-glycal addition route. They undergo ring-opening by azide or chloride ion to give, after deprotection, the 2′-substituted-4′-thionucleosides 13 and 14, whereas reactions with cyanide or fluoride sources lead to the unsaturated nucleosides 17 or 18, depending upon conditions. An unexpected and clean rearrangement to the thietane 23 occurs on treatment of uracil derivative 20 with DAST. 相似文献
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6.
Xue-qiang Yin Wei-kuan Li Minmin Yang Stewart W. Schneller 《Bioorganic & medicinal chemistry》2009,17(8):3126-3129
A synthetic route to (1S,2S,3R,5S)-3-(6-amino-9H-purin-9-yl)-5-fluorocyclopentane-1,2-diol (that is, the 4′-fluoro derivative of 4′-deoxy-5′-noraristeromycin, 3) is described via a fluorinated cyclopentanol, which is in contrast to existing schemes where fluorination occurred once the purine ring was present. Compound 3 was assayed versus a number of viruses. A favorable response was observed towards measles (IC50 of 1.2 μg/mL in the neutral red assay and 14 μg/mL by the visual assay) but this was accompanied by cytotoxicity in the CV-1 host cells (21–36 μg/mL). Among the viruses unaffected by 3 were human cytomegalovirus and the poxviruses (vaccinia and cowpox), which are three viruses that were inhibited by the 4′,4′-difluoro analog of 3 (that is, 2). 相似文献
7.
4′-Hydroxy-3,5,6,7,3′,5′-hexamethoxyflavone has been isolated from the leaves of Sri Lankan Murraya paniculata. 相似文献
8.
M. Berger A. Shaw J. Cadet J. R. Jones 《Nucleosides, nucleotides & nucleic acids》2013,32(1-2):395-396
Abstract The deuterations of 2′-deoxyguanosine in the 4′ and 5′ positions have been described elsewhere (1). The starting material is the 5′-aldehyde formed by mild oxidation with N,N-dicyclohexyl carbodiimide in dimethyl sulphoxide of the fully protected nucleoside with free 5′-alcoholic function. The 5′4euteration was achieved by reduction with deuterated sodium borohydride. Incorporation of deuterium in the 4′-position was achieved v i a an enhanced keto-enol tautomerim by heating the aldehyde in 50/50 D20/pyridine, with subsequent reduction of the aldehyde with NaBH4. The 6-furanoid form was isolated from the I-lyxo by-product by reverse phase HPLC. Applied to pyrimidine 2′-deoxyribonucleosides, this method was shown to give deuterated 2′-deoxycytidine and thymidine in good yield. 相似文献
9.
Lak Shin Jeong Hyung Ryong Moon Su Jeong Yoo Sun Nan Lee Hee-Doo Kim Moon Woo Chun 《Nucleosides, nucleotides & nucleic acids》2013,32(4-5):571-572
Abstract L-2′-Deoxy-2′-up-fluoro-4′-thionucleosides were efficiently synthesized from D-xylose via L-4-thioarabitol derivative as a key intermediate and evaluated for antiviral activities against HIV-1, HSV-1,2 and HBV. 相似文献
10.
Reaction of methyl 4′,6′-di-O-mesyl-β-lactoside pentabenzoate (8), synthesised via the 4′,6′-O-benzylidene derivative (6), with sodium azide in hexamethylphosphoric triamide gave three products. In addition to the required 4′,6′-diazidocellobioside (9), an elimination product, methyl 4-O-(6-azido-2,3-di-O-benzoyl-4,6-dideoxy-α-L-threo-hex-4-enopyranosyl)-2,3,6-tri-O-benzoyl-β-D-glucopyranoside (12), and an unexpected product of interglycosidic cleavage, methyl 2,3,6-tri-O-benzoyl-β-D-glucopyranoside (13), were formed. The origin of the latter product is discussed. The diazide 9 was converted into 4′,6′-diacetamido-4′,6′-dideoxycellobiose hexa-acetate (16) by sequential debenzoylation, catalytic reduction, acetylation, and acetolysis. 相似文献
11.
Daisuke Kaga Noriaki Minakawa Akira Matsuda 《Nucleosides, nucleotides & nucleic acids》2013,32(10-12):1789-1800
The synthesis of 2′-C-methyl-4′-thiocytidine (16) is described. Since the 2′-keto-4′-thiocytidine derivative 2β unexpectedly isomerized to 2α and the methylation of 2β proceeded predominantly from the less hindered α-face to give 7, the desired product 16 was synthesized via the Pummerer reaction of the sulfoxide 14 and N 4 -benzoylcytosine. 相似文献
12.
Qiang Wang Yanfeng Li Chuanjun Song Keduo Qian Chin-Ho Chen Kuo-Hsiung Lee Junbiao Chang 《Bioorganic & medicinal chemistry letters》2010,20(14):4053-4056
Based on the favorable antiviral profiles of 4′-substituted nucleosides, novel 1-(2′-deoxy-2′-fluoro-4′-C-ethynyl-β-d-arabinofuranosyl)-uracil (1a), -thymine (1b), and -cytosine (2) analogs were synthesized. Compounds 1b and 2 exhibited potent anti-HIV-1 activity with IC50 values of 86 and 1.34 nM, respectively, without significant cytotoxicity. Compound 2 was 35-fold more potent than AZT against wild-type virus, and also retained nanomolar antiviral activity against resistant strains, NL4-3 (K101E) and RTMDR. Thus, 2 merits further development as a novel NRTI drug. 相似文献
13.
《Nucleosides, nucleotides & nucleic acids》2013,32(4-7):747-750
A series of 4′-C-hydroxymethyl-2′-fluoro-D-arabinofuranosylpurine nucleosides was prepared and evaluated for cytotoxicity in human tumor cell lines. A convenient synthesis of the carbohydrate precursor 4-C-hydroxymethyl-3,5-di-O-benzoyl-2-fluoro-α-D-arabinofuranosyl bromide (13) was developed. Coupling of 13 with the sodium salt of 2,6-dichloropurine led to five target purine nucleosides. 相似文献
14.
L. Bellon J.-L. Barascut J.-L. Imbach 《Nucleosides, nucleotides & nucleic acids》2013,32(8):1467-1479
Abstract A synthetic pathway to reach easily the 4-thio-D-ribofuranose is described. Some corresponding pyrimidine α and β 4′-thioribonucleosides have been synthesized and evaluated as antiviral agents against various viruses. 相似文献
15.
The permeabilities of sarcoplasmic reticulum vesicle membrane for various ions and neutral molecules were measured by following the change in light scattering intensity due to the osmotic volume change of the vesicles. 4-Acetoamido-4′-isothiocyanostilbene-2,2′-disulfonate (SITS), which is a potent inhibitor for the anion permeability of red blood cells membrane, inhibited the permeability of sarcoplasmic reticulum for anions such as Cl?, Pi and methanesulfonate, while it slightly increased that for cations and neutral molecules such as Na+, K+, choline and glycerol. Binding of 5μmol SITS/g protein was necessary for the inhibition of anion permeability. These results suggest the existence of a similar anion transport system in sarcoplasmic reticulum membrane as revealed in red blood cell membrane. 相似文献
16.
Abstract A strategy based on the use of (trifluoromethyl) trimethylsilane for introduction of the trifluoromethyl group at the C-4 of ribose has been developed and utilized in the synthesis of various novel 4′-trifluoromethylated nucleoside analogs. Screening of these analogs against HIV did not reveal significant biological activity. 相似文献
17.
Synthesis of 2′-Deoxy-2′ -Fluoro-D-Arabinopyranopyranosyl Nucleosides and Their 3′,4′-Seco analogues
P. Herdewijn A. Van Aerschot R. Busson P. Claes E. De Clercq 《Nucleosides, nucleotides & nucleic acids》2013,32(7):1525-1549
Abstract 2′-Deoxy-2′-fluoro-D-arabinopyranosyl nucleosides were synthesized by condensation of 1,3,4-tri-O-benzoyl-2-deoxy-2-fluoro-D-arabinopyranose with the appropriate silylated bases in the presence of trimethylsilyl triflate. Scission of the 3′,4′-bond by periodate oxidation followed by sodium borohydride reduction resulted in the formation of the 3′,4′-seco analogues of the 2′-deoxy-2′-fluoro-D-arabinofuranosyl nucleosides. 相似文献
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19.
Novel 4′-cyclopropyl-5′-norcarbocyclic adenosine phosphonic acid analogues were designed and racemically synthesized from propionaldehyde 5 through a de novo acyclic stereoselective route using triple Grignard addition and ring-closing metathesis (RCM) as key reactions. To improve cellular permeability and enhance the anti-HIV activity of this phosphonic acid, SATE phosphonodiester nucleoside prodrug 23 was prepared. The synthesized adenosine phosphonic acids analogues 17, 18, 19, 21, and 23 were subjected to antiviral screening against HIV-1. Compound 23 exhibits enhanced anti-HIV activity than its parent nucleoside phosphonic acid 18. 相似文献
20.
Kazuhiro Haraguchi Masanori Sumino Hiromichi Tanaka 《Nucleosides, nucleotides & nucleic acids》2013,32(6-7):835-839
For the synthesis of 2′,3′ -didehydro-3′ -deoxy-4′ -C-ethynylthymidine (8: 4′ -Ed4T), a recently reported promising anti-HIV agent, a new approach was developed. Since treatment of 1-(2,5-dideoxy-β-l-glycero-pent-4-enofuranosyl)thymine with Pb(OBz)4 allowed the introduction of a 4′-benzoyloxy leaving group, nucleophilic substitution at the 4′ -position became feasible for the first time. Thus, reaction between the 4′-benzoyloxy derivative (11) and Me3SiC ≡ CAl(Et)Cl as a nucleophile led to the isolation of the desired 4′-“down”-ethynyl derivative (15) stereoselectively in 62% yield. 相似文献