- Studies on sugar puckering and glycosidic stabilities of 3′-amino-5′-carboxymethyl-3′,5′-dideoxy nucleoside mimics
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The synthesis of nucleoside amino acid monomers and dimers has been carried out to evaluate and characterize the impact of the neutral amide backbone on key attributes like puckering of the sugar rings and glycosidic bond strengths of these analogs. The conformational analysis suggests that amide-linked nucleotides have a high predilection towards N-type conformers. The glycosidic bond strength was found to be slightly weaker compared to ribonucleosides under acidic conditions at high temperatures. The results will be helpful to explore in future the development of fully amide-linked oligonucleotides for therapeutic purposes.
- Pal, Chandan,Velusamy, Arventh,Sunkari, Yashoda Krishna,Chakraborty, Tushar Kanti
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p. 6735 - 6740
(2018/09/29)
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- Synthesis of non-hydrolyzable substrate analogs for Asp-tRNAAsn/Glu-tRNAGln amidotransferase
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Non-hydrolyzable substrate analogs for tRNA-dependent amidotransferase, 2′- or 3′-aspartyl or -glutamyl adenosine, were synthesized from adenosine without protection of the adenine base. The hydroxyl groups of adenosine were selectively protected, followed by a series of oxidation/reductions to alter the stereochemistry. DFT calculations revealed the driving forces for the ketone hydrate formation at C-2′, but not the C-3′ carbon during the oxidation step. Subsequently, triflation and azide replacement yielded azidoadenosines, which were coupled to protected amino acids after deprotection and reduction. After global deprotection, the target substrate analogs were obtained in 2-14% overall yields from adenosine.
- Klinchan, Chayada,Hsu, Yu-Ling,Lo, Lee-Chiang,Pluempanupat, Wanchai,Chuawong, Pitak
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supporting information
p. 6204 - 6207
(2014/12/10)
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- A new protecting group '3′,5′-O-sulfinyl' for xylo-nucleosides. A simple and efficient synthesis of 3′-amino-3′-deoxyadenosine (a puromycin intermediate), 2,2′-anhydro-pyrimidine nucleosides and 2′,3′-anhydro-adenosine
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We developed a new protecting group, the cyclic sulfite for the protection of the 3′,5′-dihydroxy group of nucleosides. Seven cyclic sulfites, 4a-c, 5a-b, and 6a-b were prepared in high yields from the corresponding xylo-uridines 1 and 2, and xylo-adenosines 3 with thionyl chloride, respectively. Synthesis of the puromycin intermediate 8 was carried out by deprotection of the sulfite moiety through an intramolecular cyclization of the 2′-α-carbamate 7.
- Takatsuki, Ken-Ichi,Yamamoto, Makoto,Ohgushi, Sumito,Kohmoto, Shigeo,Kishikawa, Keiki,Yamashita, Haruhiro
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p. 137 - 140
(2007/10/03)
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- An efficient synthesis of 3′-amino-3′-deoxyguanosine from guanosine
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3′-Amino-3′-deoxyguanosine was synthesized from guanosine in eight steps and 58% overall yield. The 2′,3′-diol of 5′-O-[(tert-butyl)diphenylsilyl]-2-N-[(dimethylamino) methylidene]guanosine was reacted with α-acetoxyisobutyryl bromide and treated with 0.5N NH3 in MeOH to yield 9-[2′-O-acetyl-3′-bromo-5′-O-[(tertbutyl) diphenylsilyl]-3′-deoxy-β-D-xylofuranosyl]-2-N- [(dimethylamino)methylidene]guanine, which was reacted with benzyl isocyanate, NaH, and then 3.0N NaOH, and finally with Pd/C (10%) and HCO2NH4 in EtOH/AcOH to afford 3′-amino-3′-deoxyguanosine.
- Zhang, Lei,Cui, Zhiyong,Zhang, Biliang
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p. 703 - 710
(2007/10/03)
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- Syntheses of puromycin from adenosine and 7-deazapuromycin from tubercidin, and biological comparisons of the 7-aza/deaza pair
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Protection (05′) of 2′,3′-anhydroadenosine with tert-butyldiphenylsilyl chloride and epoxide opening with dimethylboron bromide gave the 3′-bromo-3′-deoxy xylo isomer which was treated with benzylisocyanate to give the 2′-O-(N-benzylcarbamoyl) derivative. Ring closure gave the oxazolidinone, and successive deprotection concluded an efficient route to 3′-amino-3′-deoxyadenosine. Analogous treatment ofthe antibiotic tubercidin {7-deazaadenosine; 4-amino-7-(β-D-ribofuranosyl)-pyrrolo[2,3-d]pyrimidine} gave 3′-amino-3′-deoxytubercidin. Trifluoroacetylation of the 3′-amino function, elaboration of the heterocyclic amino group into a (1,2,4-triazol-4-yl) ring with N,N′-bis-[(dimethylamino)methylene]hydrazine, and nucleophilic aromatic substitution with dimethylamine gave puromycin aminonucleoside [9-(3-amino-3-deoxy-β-D-ribofuranosyl)-6-(dimethylamino)purine] and its 7-deaza analogue. Aminoacylation [BOC-(4-methoxy-L-phenylalanine)] and deprotection gave puromycin and 7-deazapuromycin. Most reactions gave high yields at or below ambient temperature. Equivalent inhibition of protein biosynthesis in a rabbit reticulocyte system and parallel growth inhibition of several bacteria were observed with the 7-aza/deaza pair. Replacement of N7 in the purine ring of puromycin by "CH" has no apparent effect on biological activity.
- Robins, Morris J.,Miles, Robert W.,Samano, Mirna C.,Kaspar, Roger L.
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p. 8204 - 8210
(2007/10/03)
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- Nucleotides: Part LIX: Synthesis, characterization, and biological activities of new potential antiviral agents: (2'-5')Adenylate trimer analogs containing 3'-deoxy-3'(hexadecanoylamino)adenosine at the 2'-terminus
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Based upon 3'-amino-3'-deoxyadenosine (15), its protected 3'- hexadecanoylamino derivative 22 was chosen as starting material for the synthesis of a series of new modified 2'-5'-adenylate trimers 33-36 as potential antiviral agents. All (2'-5')A trimer analogs 33-36 inhibit HIV-1 replication as measured by the inhibition of syncytia formation and inhibition of HIV-1 reverse transcriptase activity. Compound 34 inhibits HIV- 1 reverse transcription by 100% and subsequently inhibits expression of HIV- 1 p24. However, compound 35 acts differently, since it does not inhibit HIV- 1 reverse transcription, HIV-1 integrase, or HIV-1 p24 expression. Therefore, 35 appears to exert its inhibitory effect at a later stage of HIV-1 replication, i.e., the budding process.
- Schirmeister-Tichy, Helga,Iacono, Kathryn T.,Muto, Nicholas F.,Homan, Joseph W.,Suhadolnik, Robert J.,Pfleiderer, Wolfgang
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p. 597 - 613
(2007/10/03)
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- Synthesis of 3'-azido- and 3'-amino-3'-deoxyadenosine in both enantiomeric forms
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Aminosugar nucleosides are important bioactive molecules of which puromycin, a derivative of 3'-amino-3'-deoxyadenosine, is one of the most important examples. Some azidosugar nucleosides, the synthetic precursors of the corresponding aminosugar compounds, are known to be active against HIV reverse transcriptase. We are interested in comparing the bioactivity of D- and L-enantiomers of such nucleosides. Here, the synthesis of both D- and L- enantiomers of 3'-azido- and 3'-amino-3'-deoxyadeonsine, respectively, is described. It begins with the introduction of the nitrogen functionality through a substitution reaction with inversion at C-3 of a D- or L-xylose derivative, respectively. The azidosugar is converted into an appropriate glycosyl donor which is the submitted to a glycosidation reaction according to Vorbruggen. Deprotection affords 3'azido-3'-deoxy-D/L-adenosine, our potentially antiviral target compounds, and reduction of the azido substituent leads to the aminosugar target molecules.
- Botta, Oliver,Moyroud, Elisabeth,Lobato, Cinta,Strazewski, Peter
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p. 13529 - 13546
(2007/10/03)
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- Solid-phase synthesis of carbohydrate and phosphodiester modified 2'-5' oligoadenylate analogs
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A series of 2'-5' oligoadenylate analogs containing internucleotide and ribose modifications were prepared by solid-phase methods as potential interferon mimetics. All syntheses were carried out using automated methodologies with precursors that allow for the generation of multiple combinations of modification.
- Hartsel, Stephanie A.,Marshall, William S.
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p. 2993 - 2998
(2007/10/03)
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- Synthesis of 3'-amino-3'-deoxyadenosine derivatives as potential drugs for the treatment of malaria
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A series of 3'-substituted 3'-amino-3'-deoxyadenosine analogues were synthesized and subsequently tested against the human malaria parasite Plasmodium falciparum in vitro. Several amongst them displayed pronounced antiplasmodial activities.
- Soenens,Francois,Van den Eeckhout,Herdewijn
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p. 409 - 411
(2007/10/02)
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- SYNTHESIS OF 3'-AMINO-3'-DEOXYADENOSINE FROM LEVOGLUCOSENONE
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A synthesis of 3'-amino-3'-deoxyadenosine (2) was developed by utilizing levoglucosenone (1) as a starting material through regio- and stereoselective cis-oxyamination of the carbon-carbon double bond.
- Kuno, Hideyuki,Niihata, Shigeo,Ebata, Takashi,Matsushita, Hajime
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p. 523 - 532
(2007/10/02)
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- 2',3'-Bis(2-chloroethyl)aminophosphoryl-3'-amino-3'-deoxyadenosine: A cyclic nucleotide with antitumor activity
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The synthesis of the title compound from 3'-amino-3'-deoxyadenosine in 40% yield is reported. 3'-Amino-3'-deoxyadenosine was made by an improved synthesis in 12 steps from inexpensive D-xylose in 15% overall yield. Both isomers of the title compound, separated by column chromatography, possess confirmed activity against KB tumor cell cultures.
- Okruszek,Verkade
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p. 882 - 885
(2007/10/07)
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