- 5′-O-Masked 2′-deoxyadenosine analogues as lead compounds for hepatitis C virus (HCV) therapeutic agents
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On the basis of our previous study on antiviral agents against the severe acute respiratory syndrome (SARS) coronavirus, a series of nucleoside analogues whose 5′-hydroxyl groups are masked by various protective groups such as carboxylate, sulfonate, and
- Ikejiri, Masahiro,Ohshima, Takayuki,Kato, Keizo,Toyama, Masaaki,Murata, Takayuki,Shimotohno, Kunitada,Maruyama, Tokumi
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p. 6882 - 6892
(2008/04/12)
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- Nucleic acid related compounds. 86. Nucleophilic functionalization of adenine, adenosine, tubercidin, and formycin derivatives via elaboration of the heterocyclic amino group into a readily displaced 1,2,4-triazol-4-yl substituent
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Treatment of 9-methyladenine and hydroxyl-protected derivatives of adenosine and 2′-deoxyadenosine with 1,2-bis[(dimethylamino)methylene]hydrazine and/or its dihydrochloride at elevated temperatures in appropriate solvents resulted in elaboration of the 6-amino group into a 6-(1,2,4-triazol-4-yl) substituent in excellent yields. Analogous functionalization of the amino groups of tubercidin {4-amino-7-(β-D-ribofuranosyl)pyrrolo[2,3-d]-pyrimidine} and formycin {7-amino-3-(β-D-ribofuranosyl)pyrazolo[4,3-d]pyrimidine} gave the respective 4- and 7-(1,2,4-triazol-4-yl) derivatives. Nucleophilic replacement of the triazole moiety gave the respective 6-, 4-, and 7-substituted purine, pyrrolo[2,3-d]pyrimidine, and pyrazolo[4,3-d]pyrimidine products. This first general method for "direct" nucleophilic replacement of an amino group on these nitrogen heterocycles also provides a new class of compounds for potential postsynthetic modifications after incorporation into oligonucleotides.
- Miles, Robert W.,Samano, Vicente,Robins, Morris J.
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p. 5951 - 5957
(2007/10/02)
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- SYNTHESIS OF 2-DEOXY-β-D-RIBONUCLEOSIDES AND2,3-DIDEOXY.β-D-PENTOFURANOSIDES ON IMMOBILIZED BACTERIAL CELLS
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Alginate gel-entrapped cells of auxotrophic thymine-dependent strain of E. coli catalyze the transfer of 2-deoxy-D-ribofuranosyl moiety of 2'-deoxyuridine to purine and pyrimidine bases as well as their aza and deaza analogs.All experiments invariably gave β-anomers; in most cases, the reaction was regiospecific, affording N9-isomers in the purine and N1-isomers in the pyrimidine series.Also a 2,3-dideoxynucleoside can serve as donor of the glycosyl moiety.The acceptor activity of purine bases depends only little on substitution, the only condition being the presence of N7-nitrogen atom.On the other hand, in the pyrimidine series the activity is limited to only a narrow choice of mostly short 5-alkyl and 5-halogeno uracil derivatives.Heterocyclic bases containing amino groups are deaminated; this can be avoided by conversion of the base to the corresponding N-dimethylaminomethylene derivative which is then ammonolyzed.The method was verified by isolation of 9-(2-deoxy-β-D-ribofuranosyl) derivatives of adenine, guanine, 2-chloroadenine, 6-methylpurine, 8-azaadenine, 8-azaguanine, 1-deazaadenine, 3-deazaadenine, 1-(2-deoxy-β-D-ribofuranosyl) derivatives of 5-ethyluracil, 5-fluorouracil, and 9-(2,3-deoxy-β-D-pentofuranosyl)hypoxanthine, 9-(2,3-deoxy-β-D-pentofuranosyl)-6-methylpurine, and other nucleosides.
- Votruba, Ivan,Holy, Antonin,Dvorakova, Hana,Guenter, Jaroslav,Hockova, Dana,et al.
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p. 2303 - 2330
(2007/10/02)
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- ACIDIC HYDROLYSIS OF 6-SUBSTITUTED 9-(2-DEOXY-β-D-ERYTHRO-PENTOFURANOSYL)PURINES AND THEIR 9-(1-ALKOXYETHYL) COUNTERPARTS: KINETICS AND MECHANISM.
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The rate constants for the hydrolysis of several 6-substituted 9-(2-deoxy-β-D-erythro-pentofuranosyl)purines and 9-(1-alkoxyethyl)purines have been measured at different concentrations of oxonium ion.The effects that varying the polar nature of the alkoxy group exerts on the hydrolysis of unsubstituted 9-(1-alkoxyethyl)purines are interpreted to indicate that the reaction proceeds by a rate-limiting departure of the protonated base moiety with a concomitant formation of an alkoxyethyl oxocarbenium ion.The same mechanism is applied to the hydrolysis of 9-(2-deoxy-β-D-erythro-pentofuranosyl)purines by comparing the influences that 6-substituents have on the reactivity of these compounds and their 9-(1-alkoxyethyl) counterparts.No sign of anomerisation was detected, when the hydrolysis of 2'-deoxyadenosine was followed by 1H NMR spectroscopy.
- Oivanen, Mikko,Loennberg, Harri,Zhou, Xiao-xiong,Chattopadhyaya, Jyoti
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p. 1133 - 1140
(2007/10/02)
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- Methylation of Adenosine and Related Nucleosides with Trimethylselenonium Hydroxyde, and Regiospecific Effects of Copper(II) Ions
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Methylation of adenosine, deoxyadenosine, 6-N-methyladenosine and 2'(3')-O-methyladenosines with trimethylselenonium hydroxyde was studied in the presence and absence of copper(II) acetylacetonate .It was found that copper(II) ions promoted methylation of the 2'(3')-OH groups of the ribonucleosides but suppressed methylation at the N-1 position of the adenine rings.The metal-ion effects are discussed in conjunction with a catalytic role for Cu(AA)2 in the reactions.
- Yamauchi, Kiyoshi,Hattori, Kazue,Kinoshita, Masayoshi
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p. 1327 - 1330
(2007/10/02)
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- Methylation study of ribonucleosides, deoxyribonucleosides, and 2′-O-methylribonucleosides with trimethylsulphonium hydroxide and trimethylsulphonium iodide. Influence of the 2′-hydroxy-groups on the reactivity of the base moieties of ribonucleosides
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Methylations of the naturally occuring ribonucleoside (1), deoxyribonucleoside (2), and 2′-O-methylribonucleoside (3) were carried out using trimethylsulphonium hydroxide (Me3SOH) and trimethylsulphonium iodide (Me3Sl). The base moiety of (2) and (3) are more reactive than the corresponding base moiety of (1). The sites and extent of methylation of (2) are considerably different from those of (1), but are almost identical with those of (3). The reactivities of (1)-(3) are discussed in connection to an intramolecular interaction of the 2′-OH groups with the base moiety of (1). The methylating characteristics of Me 3SOH and Me3Sl are also described. The kinetics indicate an SN2 mechanism for methylation of nucleosides by Me 3S+ ions.
- Yamauchi, Kiyoshi,Nakagima, Toru,Kinoshita, Masayoshi
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p. 2787 - 2792
(2007/10/02)
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