- Synthesis of 3′-azido-4′-ethynyl-3′,5′-dideoxy- 5′-norarabinouridine: A new anti-HIV nucleoside analogue
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3′-Azido-4′-ethynyl-3′,5′dideoxy-5′- norarabinouridine 10 was synthesized from commercial uridine 1 in which the key step is the opening of protected 2′,3′-epoxyuridine derivative 7 by sodium azide and the hydroxymethyl at 4-position of the ribose ring are replaced by ethynyl group.
- Amin, Mahmoud A.
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experimental part
p. 1703 - 1708
(2011/04/18)
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- 3′-Bromo analogues of pyrimidine nucleosides as a new class of potent inhibitors of mycobacterium tuberculosis
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Tuberculosis (TB) is a major health problem worldwide. We herein report a new class of pyrimidine nucleosides as potent inhibitors of Mycobacterium tuberculosis (M. tuberculosis). Various 2′- or 3′-halogeno derivatives of pyrimidine nucleosides containing uracil, 5-fluorouracil, and thymine bases were synthesized and evaluated for antimycobacterial activities. Among the compounds tested, 3′-bromo-3′-deoxy- arabinofuranosylthymine (33) was the most effective antituberculosis agent in the in vitro assays against wild-type M. tuberculosis strain (H37Ra) (MIC 50 = 1 μg/mL) as well as drug-resistant (H37Rv) (rifampicin-resistant and isoniazid-resistant) strains of M. tuberculosis (MIC50 = 1-2 μg/mL). Compound 33 also inhibited intracellular M. tuberculosis in a human monocytic cell line infected with H37Ra, demonstrating higher activity against intramacrophagic mycobacteria (80% reduction at 10 μg/mL concentration) than extracellular mycobacteria (75% reduction at 10 μg/mL concentration). In contrast, pyrimidine nucleosides possessing 5-fluorouracil base were weak inhibitors of M. tuberculosis. No cytotoxicity was found up to the highest concentration of compounds tested (CC50 > 100-200 μg/mL) against a human cell line. Overall, these encouraging results substantiate the potential of this new class of compounds as promising antituberculosis agents.
- Shakya, Neeraj,Srivastav, Naveen C.,Desroches, Nancy,Agrawal, Babita,Kunimoto, Dennis Y.,Kumar, Rakesh
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experimental part
p. 4130 - 4140
(2010/09/04)
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- Preparation and cleavage reactions of 3′-thiouridylyl-(3′→5′)-uridine
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3′-Thiouridylyl-(3′→5′)-uridine [(Us)pU] 3 is prepared by coupling together the disulfide 14 and the 5′-H-phosphonate 18, and then removing the protecting groups. (Us)pU 3 readily undergoes cleavage in 0.05 mol dm-3 sodium glycinate buffer (pH 10.06) at 50 °C to give, in the first instance, uridine 4 and 3′-thiouridine 2′,3′-cyclic phosphorothioate 21; in glacial acetic acid at 30 °C, it rapidly undergoes cleavage in essentially the same way. The behaviour of (Us)pU 3 is compared with that of uridylyl-(3′→5′)-uridine (UPU) 1a under the same basic and acidic reaction conditions. (Us)pU 3 and 3′-thiouridine 2′,3′-cyclic phosphorothioate 21 are both substrates for ribonuclease A; (Us)pU 3 is a substrate for Crotalus adamanteus snake venom phosphodiesterase but not for calf spleen phosphodiesterase.
- Liu, Xiaohai,Reese, Colin B.
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p. 2227 - 2236
(2007/10/03)
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- Synthesis of 2',3'-dideoxy-3'-hydroxymethylcytidine; A unique antiviral nucleoside
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The synthesis of 2',3'-dideoxy-3'-hydroxymethylcytidine 1 was accomplished using two different approaches. First, uridine and cytidine were used to prepare the key intermediate epoxides 15 and 31 which were opened with cyanide, deoxygenated by elimination to vinyl nitriles 17 and 36, and reduced by 1,4 hydride addition to the saturated nitriles 18 and 37. Secondly, a novel Rh-catalyzed hydroformylation reaction of 2',3'-didehydro-2',3'-dideoxycytidine 46 was used to prepare 1 in four steps. The attempted use of 2'-deoxyuridine and 2'-deoxycytidine to prepare 1 is also discussed.
- Faul, Margaret M.,Huff, Bret E.,Dunlap, Steven E.,Frank, Scott A.,Fritz, James E.,Kaldor, Stephen W.,LeTourneau, Michael E.,Staszak, Michael A.,Ward, Jeffrey A.,Werner, John A.,Winneroski, Leonard L.
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p. 8085 - 8104
(2007/10/03)
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- Synthesis of 2′,3′-didehydro-2′,3′-dideoxynucleosides by reaction of 5′-protected nucleoside 2′,3′-dimesylates with telluride dianion: A general route from cis vicinal diols to olefins
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2′,3′-Dimesylates of 5′-protected nucleosides are converted into the corresponding 2′,3′-didehydro2′,3′-dideoxy compounds by treatment with telluride dianion in the form of the sodium or lithium salt. The method is well-suited to the preparation of unsaturated nucleosides that can be converted into compounds that are believed to be useful in the treatment of AIDS. The deoxygenation is general for vicinal dimesylates that have, or may adopt, a synperiplanar conformation. With straight chain compounds the reaction is stereospecific. In some cases, similar, but slower, deoxygenations can be performed with selenide dianion.
- Clive, Derrick L. J.,Wickens, Philip L.,Sgarbi, Paulo W. M.
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p. 7426 - 7437
(2007/10/03)
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- Deoxygenation of cis vicinal diols to make didehydro dideoxy nucleosidies and synthetic intermediates
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Cis vicinal diols are converted to olefins using tellurides or selenide reagents. The diol is reacted to convert the hydroxyl groups into good leaving groups for nucleophilic substitution. Alkyl and aryl sulfonate groups such as mesylate or tosylate are p
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- Synthesis of 2',3'-Dithiouridine
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The synthesis of 2',3'-dithiouridine 2, starting from uridine, is described.
- Johnson, Richard,Joshi, Bhalchandra V.,Reese, Colin B.
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p. 133 - 134
(2007/10/02)
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