2‘-Amino-2‘-deoxyuridine <i>via </i>an Intramolecular Cyclization of a Trichloroacetimidate

McGee, Danny P. C.; Vaughn-Settle, Alecia; Vargeese, Chandra; Zhai, Yansheng

doi:10.1021/jo9510548

Cited by 70 publications

(50 citation statements)

References 21 publications

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“…[31] For these ligands, either 5'-aminodeoxythymidine or 2'-aminodeoxyuridine was used as the starting material. [32,33] The tridentate chelate functionality was then introduced by either direct reductive amination with pyridine-2-carboxaldehyde or by amide formation with a HOBt-activated ester of a pre-derivatized 5-aminovaleric acid analogue. We recently reported a series of compounds, dubbed single amino acid chelates (SAACs), which can be conveniently obtained from commercially available amino acids in a single reaction step either by nucleophilic substitution with 2-chloromethylpydridine (for 27) or reductive amination with pyridine-2-carboxaldehyde and sodium triacetoxyborohydride in dichloroethane (DCE; for 28-31), as illustrated in Scheme 1; these served as building blocks in the synthesis of complexes 47, 48, and 54-58.…”

Section: Ligand Synthesesmentioning

confidence: 99%

“…Compound 28 (1.50 g, 5.22 mmol) was dissolved in an aqueous solution of 0.1 m NaOH (50 mL) and stirred at room temperature for 16 h. The solution was neutralized to pH 7 with 1 m HCl, and the aqueous phase was then extracted with CH 2 Cl 2 (3 30 mL). The combined organic layers were dried using anhydrous Na 2 SO 4 (33). Compound 27 (0.13 g, 0.53 mmol) was dissolved in anhydrous DMF (20 mL) under an inert atmosphere (argon) followed by the addition of 1-hydroxybenzotriazole (HOBt; 0.078 g, 0.58 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (EDC; 0.11 g, 0.58 mmol), and anhydrous Et 3 N (0.26 mL, 1.84 mmol).…”

Section: -((2r4s5r)-5-((8-aminooctyloxy)methyl)-4-hydroxytetrahydrmentioning

confidence: 99%

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Synthesis, Cytotoxicity, and Insight into the Mode of Action of Re(CO)₃ Thymidine Complexes

Bartholomä¹,

Vortherms²,

Hillier³

et al. 2010

ChemMedChem

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Nucleoside analogues are extensively used in the treatment of cancer and viral diseases. The antiproliferative properties of organorhenium(I) complexes, however, have been scarcely explored to date. Herein we present the syntheses, characterization, and in vitro evaluation of Re(I)(CO)(3) core complexes of thymidine and uridine. For the binding of the Re(I)(CO)(3) core, a tridentate dipicolylamine metal chelate was introduced at positions C5', C2', N3, and C5 with spacers of various lengths. The corresponding organometallic thymidine complexes were fully characterized by IR and NMR spectroscopy and mass spectrometry. Their cytotoxicity was assessed against the A549 lung carcinoma cell line. Toxicity is dependent on the site and mode of conjugation as well as on the nature and the length of the tether. Moderate toxicity was observed for conjugates carrying the rhenium moiety at position C5' or N3 (IC(50)=124-160 microM). No toxicity was observed for complexes modified at C2' or C5. Complex 53, with a dodecylene spacer at C5', exhibits remarkable toxicity and is more potent than cisplatin, with an IC(50) value of 6.0 microM. To the best of our knowledge, this is the first report of the antiproliferative properties of [M(CO)(3)](+1)-nucleoside conjugates. In competitive inhibition experiments with A549 cell lysates and purified recombinant human thymidine kinase 1 (hTK-1), enzyme inhibition was observed for complexes modified at either N3 or C5', but our results suggest that the toxicity cannot be attributed solely to interaction with hTK-1.

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Section: Ligand Synthesesmentioning

confidence: 99%

Section: -((2r4s5r)-5-((8-aminooctyloxy)methyl)-4-hydroxytetrahydrmentioning

confidence: 99%

Synthesis, Cytotoxicity, and Insight into the Mode of Action of Re(CO)₃ Thymidine Complexes

Bartholomä¹,

Vortherms²,

Hillier³

et al. 2010

ChemMedChem

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“…Modified nucleoside precursors were prepared by reaction of the protected 2'-aminonucleoside [13] with the Nhydroxysuccinimidyl ester of the appropriate azobenzene, [14] and subsequently phosphitylated under standard conditions. These precursors were incorporated into model octamers (ACC1GGTA) and also 10-23 deoxyribozyme sequences (Scheme 1 b) by automated solid-phase synthesis with extended reaction times for introduction of the modified residue.…”

mentioning

confidence: 99%

Reversible Photocontrol of Deoxyribozyme‐Catalyzed RNA Cleavage under Multiple‐Turnover Conditions

Keiper

Vyle

2006

Angew Chem Int Ed

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“…30,31 However, applying such pathways would involve multiple steps. Here, we aimed at a one-step protecting group-free synthesis using the substrates 2,2′-anhydrouridine 1 and 2-azidoethanol (which are commercially available or can be prepared by a single transformation from the precursors uridine 32 and 2-chloroethanol, 33 respectively) in the presence of boron trifluoride diethyl etherate (Scheme 1). The procedure was eleborated based on reports by Egli 34 and Sekine 35 who demonstrated the corresponding transformation with a series of other alcohol derivatives.…”

Section: Resultsmentioning

confidence: 99%

Efficient Access to 3′-Terminal Azide-Modified RNA for Inverse Click-Labeling Patterns

et al. 2013

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Labeled RNA becomes increasingly important for molecular diagnostics and biophysical studies on RNA with its diverse interaction partners, which range from small metabolites to large macromolecular assemblies, such as the ribosome. Here, we introduce a fast synthesis path to 3′-terminal 2′-O-(2-azidoethyl) modified oligoribonucleotides for subsequent bioconjugation, as exemplified by fluorescent labeling via Click chemistry for an siRNA targeting the brain acid-soluble protein 1 gene (BASP1). Importantly, the functional group pattern is inverse to commonly encountered alkyne-functionalized “click”-able RNA and offers increased flexibility with respect to multiple and stepwise labeling of the same RNA molecule. Additionally, our route opens up a minimal step synthesis of 2′-O-(2-aminoethyl) modified pyrimidine nucleoside phosphoramidites which are of widespread use to generate amino-modified RNA for N-hydroxysuccinimide (NHS) ester-based conjugations.

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2‘-Amino-2‘-deoxyuridine via an Intramolecular Cyclization of a Trichloroacetimidate

Cited by 70 publications

References 21 publications

Synthesis, Cytotoxicity, and Insight into the Mode of Action of Re(CO)₃ Thymidine Complexes

Synthesis, Cytotoxicity, and Insight into the Mode of Action of Re(CO)₃ Thymidine Complexes

Reversible Photocontrol of Deoxyribozyme‐Catalyzed RNA Cleavage under Multiple‐Turnover Conditions

Efficient Access to 3′-Terminal Azide-Modified RNA for Inverse Click-Labeling Patterns

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2‘-Amino-2‘-deoxyuridine via an Intramolecular Cyclization of a Trichloroacetimidate

Cited by 70 publications

References 21 publications

Synthesis, Cytotoxicity, and Insight into the Mode of Action of Re(CO)3 Thymidine Complexes

Synthesis, Cytotoxicity, and Insight into the Mode of Action of Re(CO)3 Thymidine Complexes

Reversible Photocontrol of Deoxyribozyme‐Catalyzed RNA Cleavage under Multiple‐Turnover Conditions

Efficient Access to 3′-Terminal Azide-Modified RNA for Inverse Click-Labeling Patterns

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Synthesis, Cytotoxicity, and Insight into the Mode of Action of Re(CO)₃ Thymidine Complexes

Synthesis, Cytotoxicity, and Insight into the Mode of Action of Re(CO)₃ Thymidine Complexes