共查询到20条相似文献,搜索用时 15 毫秒
1.
Saúl Martínez-Montero Susana Fernández Yogesh S. Sanghvi Emmanuel A. Theodorakis Mervi A. Detorio Tamara R. Mcbrayer Tony Whitaker Raymond F. Schinazi Vicente Gotor Miguel Ferrero 《Bioorganic & medicinal chemistry》2012,20(23):6885-6893
A series of 2′,3′-dideoxy-2′,2′-difluoro-4′-azanucleosides of both pyrimidine and purine nucleobases were synthesized in an efficient manner starting from commercially available L-pyroglutamic acid via glycosylation of difluorinated pyrrolidine derivative 15. Several 4′-azanucleosides were prepared as a separable mixture of α- and β-anomers. The 6-chloropurine analogue was obtained as a mixture of N7 and N9 regioisomers and their structures were identified based on NOESY and HMBC spectral data. Among the 4′-azanucleosides tested as HIV-1 inhibitors in primary human lymphocytes, four compounds showed modest activity and the 5-fluorouracil analogue (18d) was found to be the most active compound (EC50 = 36.9 μM) in this series. None of the compounds synthesized in this study demonstrated anti-HCV activity. 相似文献
2.
Kohei Yamada Hiroyuki Hayakawa Shinji Sakata Noriyuki Ashida Yuichi Yoshimura 《Bioorganic & medicinal chemistry letters》2010,20(20):6013-6016
We have identified a selective SN2′ reaction triggered by iodide ion that leads to the ring-opening of 2,2′-anhydro-α-nucleosides. By applying the method, we have synthesized α-d-2′,3′-didehydro-2′,3′-dideoxy-3′-C-hydroxymethyl nucleosides, designed as potential antiviral agents. 相似文献
3.
《Bioorganic & medicinal chemistry》2014,22(21):6174-6182
Upon reacting 3′,4′-unsaturated cytosine (8 and 9) and adenine nucleosides (13 and 14) with XeF2/BF3·OEt2, the respective novel 3′,4′-difluoro-3′-deoxyribofuranosyl nucleosides (10–12 and 15–18) could be obtained. Formation of anti-adducts (11, 16 and 18) revealed that the fluorination involved oxonium ions as incipient intermediates. TBDMS-protected 3′,4′-unsaturated adenosine provided the β-face adducts as sole stereoisomers whereas α-face-selectivity was observed with the TBDPS-protected adenosine 14. The evaluation of the novel 3′-deoxy-3′,4′-difluororibofuranosylcytosine-(19–21) and adenine nucleosides (22–25) against antitumor and antiviral activities revealed that 3′,4′-difluorocordycepin (24) was found to possess anti-HCV activity. The SI of 24 was comparable to that of the anti-HCV drug ribavirin. However, sofosbuvir, FDA-approved novel anti-HCV drug, showed better SI value. Our finding revealed that the introduction of the fluoro-substituent into the 4′-position of cordycepin derivatives decreased the cytotoxicity to the host cell with retention of the antiviral activity. 相似文献
4.
Zhe Chen Bryan D. Cox Ethel C. Garnier-Amblard Tamara R. McBrayer Steven J. Coats Raymond F. Schinazi Franck Amblard 《Bioorganic & medicinal chemistry letters》2017,27(23):5296-5299
Several β-d-2′-deoxy-2′-substituted nucleoside analogs have displayed potent and selective anti-HCV activities and some of them have reached human clinical trials. In that regard, we report herein the synthesis of a series of 2′-deoxy,2′-dibromo substituted U, C, G and A nucleosides 10a–d and their corresponding phosphoramidate prodrugs 13a–d. The synthesized nucleosides 10a–d and prodrugs 13a–d were evaluated for their inhibitory activity against HCV as well as cellular toxicity. The results showed that the most potent compound was prodrug 13a, which exhibited micromolar inhibitory activity (EC50?=?1.5?±?0.8?µM) with no observed toxicity. In addition, molecular modeling and free energy perturbation calculations for the 5′-triphosphate formed from 13a and related 2′-modified nucleotides are discussed. 相似文献
5.
Yutaka Kubota Nobuhide Ishizaki Kazuhiro Haraguchi Takayuki Hamasaki Masanori Baba Hiromichi Tanaka 《Bioorganic & medicinal chemistry》2010,18(20):7186-7192
Synthesis of the 4′-ethynyl and 4′-cyano phosphonates 8–11, which mimic the 5′-monophosphate of 4′-branched 2′,3′-didehydro-2′,3′-dideoxy nucleosides, was investigated by employing the 3′,4′-unsaturated nucleosides (13 and 28) as the starting material. The synthesis was initiated by the electrophilic addition of NIS/(EtO)2P(O)CH2OH to these unsaturated nucleosides. After introduction of the 2′,3′-double bond, the 4′-hydroxylmethyl group of the resulting adducts was transformed into the ethynyl or cyano group. While the 4′-cyano phosphonates 9 and 11 were not sufficiently stable to be isolated, the 4′-ethynyl counterparts (8 and 10) were obtained as their mono-ammonium salts. The adenine derivative 8 showed almost comparable anti-HIV-1 activity to that of d4T. 相似文献
6.
Shinya KIKUCHI Tomohiro MAEKAWA Katsumaro MINAMOTO Keizo TANIGAWA 《Nucleosides, nucleotides & nucleic acids》2013,32(8):1365-1372
Abstract 2′,3′-Dibromo-2′,3′-dideoxy-5′-O-trityl-2′,3′-secouridine (8) with sdKF gave the 3′,4′-didehydro-2,2′-anhydro nucleoside 9, which was deprotected to 10. Hydrolysis of 9 gave 3′,4′-didehydro-3′-deoxy-5′-O-trityl-2′,3′-secouridine (11a). Similarly, compound 9 with pyridinium halides gave the corresponding 2′-deoxy-2′-halo nucleosides (11b-d). Compound 11d with azide ion gave 2′-azido analogue 11e. Compound 9 with an excess amount of azide ion gave the 2′-azido triazole (13). 相似文献
7.
Hong-wang Zhang Steven J. Coats Lavanya Bondada Franck Amblard Mervi Detorio Ghazia Asif Emilie Fromentin Sarah Solomon Aleksandr Obikhod Tony Whitaker Nicolas Sluis-Cremer John W. Mellors Raymond F. Schinazi 《Bioorganic & medicinal chemistry letters》2010,20(1):60-64
Based on the promising drug resistance profile and potent anti-HIV activity of β-d-3′-azido-2′,3′-dideoxyguanosine, a series of purine modified nucleosides were synthesized by a chemical transglycosylation reaction and evaluated for their antiviral activity, cytotoxicity, and intracellular metabolism. Among the synthesized compounds, several show potent and selective anti-HIV activity in primary lymphocytes. 相似文献
8.
Jin-Lan Yu Qin-Pei Wu Qing-Shan Zhang Yan-Hong Liu Yun-Zheng Li Zi-Ming Zhou 《Bioorganic & medicinal chemistry letters》2010,20(1):240-243
A series of novel 2′,3′-dideoxy-2′,3′-diethanethioribonucleosides and those modified with a triazole ring were prepared in excellent yields and their antitumor activity was evaluated. Nucleosides with a triazole ring, 16a–16c, showed significantly improved activity towards a broad range of tumor cell lines. 相似文献
9.
Jesper Wengel Kirsten Østergaard Anders Hager 《Nucleosides, nucleotides & nucleic acids》2013,32(7-8):1361-1368
Abstract The regio- and stereoselective photocatalysed addition of 2-propanol and cyclopentanol to (5S)-hydroxymethylfuran-2(5H)-one (1) gave 4-C-branched lactones 2 and 3 after selective silylations. The lactones 2 and 3 were radically deoxygenated affording lactones 4 and 5, respectively. As an example, compound 2 was transformed without purification of the intermediates into an anomeric mixtures of deprotected 3′-C-branched 2′, 3′-dideoxynucleosides 6 by the following reaction sequence: silylation, reduction, acetylation, coupling with silylated thymine and desilylation. 相似文献
10.
Frederick A. Luzzio Alexander V. Mayorov Michael E. Menes William L. Champion Jr. 《Nucleosides, nucleotides & nucleic acids》2013,32(9):1977-1984
Abstract The stereoselective preparation of a 4-methyl-2,3-dideoxyribose derivative is described which utilizes (-)-menthyl pyruvate as a chiral template and an organocerium addition as the key carbon-carbon bond-forming step. The 4-methyl-2,3-dideoxyribose derivative was used as a substrate for a Vorbrüggen pyrimidine glycosylation giving an α, β-mixture of 4′-methyl-2′,3′-dideoxynucleosides. 相似文献
11.
Won Jun Choi Yu Min Kim Hea Ok Kim Hyuk Woo Lee Dong-Eun Kim Kwang-su Park Youhoon Chong Lak Shin Jeong 《Bioorganic & medicinal chemistry》2010,18(13):4812-4820
On the basis of potent anti-hepatitis C virus (HCV) activity of 2′-C-hydroxymethyladenosine, 3′-C-substituted-methyl-ribofuranosyl pyrimidine and purine nucleosides were designed and synthesized from d-xylose. Among compounds tested, all adenine analogues, 4a, 4d, and 4g showed significant anti-HCV activity in a replicon-based cell assay irrespective of the substituent (Y = OH, N3, or F) at the 3′-C-substituted methyl position, among which 4g (Y = N3) was the most potent, but it is also cytotoxic. This study guarantees the 3′-C-substituted-methyl nucleoside serves as a new template for the development of new anti-HCV agents. 相似文献
12.
Magnus Björsne Björn Classon Inger Kers Bertil Samuelsson Ingemar Kvarnström 《Nucleosides, nucleotides & nucleic acids》2013,32(3-5):283-286
Abstract Some 2′,3′-dideoxy-3′, 4′-dihydroxymethyl nucleoside analogues have been synthesised starting from diacetone-D-glucose. The 3-C-hydroxymethyl group was introduced by selective hydroboration-oxidation of the 3-C-methylene derivative. The 4-C-hydroxymethyl group was obtained by an aldol condensation followed by in situ cross Canizzaro reduction. Glycosylation using silylated pyrimidine bases furnished the 2′,3′-dideoxy-3′,4′-dihydroxymethyl nucleoside analogues. 相似文献
13.
《Phytochemistry》1996,42(5):1259-1262
Methyl 5′,5′,5′-trifluorojasmonate was synthesized as an antimetabolic analogue of methyl jasmonate. It induced potato tuber formation more effectively than methyl jasmonate and inhibited the growth of rice seedlings and the germination of lettuce and radish seeds. These results suggest that epijasmonic acid itself has potato tuber-inducing activity and that the hydroxyl group of tuberonic acid is not necessary for this activity. 相似文献
14.
Åsa Lundquist Ingemar Kvarnström Stefan C. T. Svensson Björn Classon Bertil Samuelsson 《Nucleosides, nucleotides & nucleic acids》2013,32(7):1493-1502
Abstract The synthesis of 3′,4′-bishydroxymethyl-2′,3′,4′-trideoxy pentopyranosyl derivatives of thymine, uracil, cytosine, and adenine is described. trans-(3S,4S)-Bis(methoxycarbonyl)cyclopentanone (3) was converted to 1-O-acetyl-3,4-C-bis[(tert-butyldiphenylsiloxy)methyl]-2,3,4-trideoxy-α,β-L-threo-pentopyranose (6), which was subsequently condensed with the silylated purine and pyrimidine bases. 相似文献
15.
Yogesh S. Sanghvi Naeem B. Hanna Steven B. Larson Roland K. Robins Ganapathi R. Revankar 《Nucleosides, nucleotides & nucleic acids》2013,32(4):761-774
Abstract A synthesis of 1-(2,3-dideoxy-β-D-ribofuranosyl)-1,2,4-triazole-3-carboxamide (2′,3′-dideoxyribavirin, ddR) is described. Glycosylation of the sodium salt of 1,2,4-triazole-3-carbonitrile (5) with 1-chloro-2-deoxy-3,5-di-0-p-toluoyl-α-D-erythro-pentofuranose (1) gave exclusively the corresponding N-1 glycosyl derivative with β-anomeric configuration (6), which on ammonolysis provided a convenient synthesis of 2′-deoxyribavirin (7). Similar glycosylation of the sodium salt of methyl 1,2,4-triazole-3-carboxylate (2) with 1 gave a mixture of corresponding N-1 and N-2 glycosyl derivatives (3) and (4), respectively. Ammonolysis of 3 furnished yet another route to 7. A four-step deoxygenation procedure using imidazolylthiocarbonylation of the 3′-hydroxy group of 5′-0-toluoyl derivative (9a) gave ddR (11). The structure of 11 was proven by single crystal X-ray studies. In a preliminary in vitro study ddR was found to be inactive against HIV retrovirus. 相似文献
16.
L. De Napoli A. Messere D. Montesarchio G. Piccialli C. Santacroce 《Nucleosides, nucleotides & nucleic acids》2013,32(8):1719-1728
Abstract Reaction of 5′-0-(4,4′-dimethoxytriphenylmethyl)-3′-deoxythy-midine with triphenylphosphine/carbon tetrachloride, followed by deprotection of the 5′-hydroxyl group, afforded the 4-chloro derivative 3 from which some 4-substituted pyrimidin-2(1H)one-2′, 3′-dideoxyribosides were obtained by nucleo-philic substitution under very mild conditions. 相似文献
17.
Victor E. Marquez Lak S. Jeong Marc C. Nicklaus Cliff George 《Nucleosides, nucleotides & nucleic acids》2013,32(3-5):555-558
Abstract The efficient DAST fluorination of deoxy-4′-thiopyrimidine nucleosides is reported. The cytidine analogue 3b was marginally effective against HIV. 相似文献
18.
K. V. Antonov I. D. Konstantinova A. I. Miroshnikov 《Nucleosides, nucleotides & nucleic acids》2013,32(1-3):153-159
Abstract A new approach to the synthesis of 2′,3′-dideoxyadenosine and 2′,3′-dideoxyinosine based on deoxygenation of 2′,3′-di-O-mesylnucleosides was developed. 相似文献
19.
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
20.
Lars Svansson Ingemar Kvarnström Björn Classon Bertil Samuelsson 《Nucleosides, nucleotides & nucleic acids》2013,32(7):1353-1366
Abstract The synthesis of 3′-C-fluoromethyl and 3′-C-azidomethyl nucleosides is reported. The 3′-C-fluoromethyl furanoside 4 was synthesized via fluoride ion induced displacement of the corresponding trifluoromethanesulfonate. The 3′-C-hydroxymethyl furanoside 3 was converted to the corresponding 3′-C-azidomethyl furanoside 6 using triphenylphosphine-carbon tetrabromide-lithium azide. The 3′-C-fluoromethyl furanoside derivative 5 and the 3′-C-azidomethyl furanoside derivative 7 were subsequently condensed with silylated purine and pyrimidine bases. Deblocking and separation of the anomers by chromatography afforded the α- and β-nucleoside analogues. The nucleosides were tested for inhibition of HIV multiplication in vitro and were found to be inactive in the assay. 相似文献