Synthesis of nucleoside 5′-O-α,β-methylene-β-triphosphates and evaluation of their potency towards inhibition of HIV-1 reverse transcriptase

Ahmadibeni, Yousef; Dash, Chandravanu; Hanley, Michael; Grice, Stuart F. J. Le; Agarwal, Hitesh K.; Parang, Keykavous

doi:10.1039/b922846b

Cited by 7 publications

(5 citation statements)

References 33 publications

(24 reference statements)

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“…generated NDPs and NTPs in good yields and purity by using polymer-bound di-and triphosphitylating reagents. [12][13][14] Peyrottes et al used polyethylene glycol (PEG) as a soluble support to generate the 5'-mono-, -di-, and triphosphates of (2'-deoxy)cytidine with the nucleoside an-A C H T U N G T R E N N U N G chored through the amino function of the heterocyclic base. [15] However, other nucleobases were not included (adenine or guanine) and the method cannot be applied to thymine or uracil.…”

Section: Introductionmentioning

confidence: 99%

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Solid‐Phase Synthesis of (Poly)phosphorylated Nucleosides and Conjugates

Tonn

Meier

2011

Chemistry A European J

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Succinyl-cycloSal-phosphate triesters of ribo- and 2'-deoxyribonucleosides were attached to aminomethyl polystyrene as an insoluble solid support and reacted with phosphate-containing nucleophiles yielding nucleoside di- and triphosphates, nucleoside diphosphate sugars, and dinucleoside polyphosphates in high purity after cleavage from the solid support. Here, reactive cycloSal-phosphate triesters were used as immobilized reagents that led to a generally applicable method for the efficient synthesis of phosphorylated biomolecules and phosphate-bridged bioconjugates.

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Section: Introductionmentioning

confidence: 99%

“…By starting from immobilized nucleosides the methods are characterized by moderate yields and low purity after cleavage,3, 8–11 whereas only Parang et al. generated NDPs and NTPs in good yields and purity by using polymer‐bound di‐ and triphosphitylating reagents 12–14. Peyrottes et al.…”

Section: Introductionmentioning

confidence: 99%

Solid‐Phase Synthesis of (Poly)phosphorylated Nucleosides and Conjugates

Tonn

Meier

2011

Chemistry A European J

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“…23,24 In continuation of our efforts to design a diverse array of modified nucleoside triphosphates as RT inhibitors, we report here the synthesis of β- triphosphotriester pronucleotides ( 1a – c ) of NRTIs, including 3′-fluoro-3′-deoxythymidine (Alovudine, FLT), 2′,3′-dideoxy-3′-thiacytidine (Lamivudine, 3TC), and 2′,3′-dideoxy-5-fluoro-3′-thiacytidine (Emtricitabine, FTC) (Fig. 1).…”

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confidence: 99%

Synthesis of β-triphosphotriester pronucleotides

Beni

Dash

Parang

2015

Tetrahedron Letters

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Dinucleoside phosphorochloridite were synthesized from phosphorus trichloride and three nucleoside analogues, 3′-fluoro-2′,3′-dideoxythymidine (FLT), 2′,3′-dideoxy-5-fluoro-3′-thiacytidine (FTC), and 2′,3′-dideoxy-3′-thiacytidine (3TC), in a multistep synthesis. Polymer-bound N-Boc p-acetoxybenzyl 5′-O-2′-deoxythymidine was reacted with dinucleoside phosphorochloridite in the presence of 2,6-lutidine, followed by the reaction with dodecyl alcohol and 5-(ethylthio)-1H-tetrazole, oxidation with tert-butyl hydroperoxide, and acidic cleavage, respectively, to afford the β-triphosphotriester derivatives containing three different nucleosides.

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“…26,27 In continuation of our efforts to design a diverse array of modified nucleoside triphosphates as RT inhibitors, we herein report the synthesis of nucleoside β-triphosphate analogs ( 1–4 ) of adenosine and NRTIs, such as 3′-azido-3′-deoxythymidine (zidovudine, AZT), 3′-fluoro-3′-deoxythymidine (alovudine, FLT), and 2′,3′-didehydro-2′,3′-dideoxythymidine (stavudine, d4T) (Fig. 1) and their inhibitory activity against the DNA polymerase of wild-type and multidrug resistant RTs.…”

mentioning

confidence: 99%

Inhibition of multi-drug resistant HIV-1 reverse transcriptase by nucleoside β-triphosphates

Dash

Ahmadibeni

Hanley

et al. 2011

Bioorganic & Medicinal Chemistry Letters

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Despite the success of potent reverse transcriptase (RT) inhibitors against human immunodeficiency virus type 1 (HIV-1) in combination regimens, the development of drug resistant RTs constitutes a major hurdle for the long-term efficacy of current antiretroviral therapy. Nucleoside β-triphosphate analogs of adenosine and nucleoside reverse transcriptase inhibitors (NRTIs) (3′-azido-2′,3′-dideoxythymidine (AZT), 3′-fluoro-2′,3′-dideoxythymidine (FLT), and 2′,3′-didehydro-2′,3′-dideoxythymidine (d4T)) were synthesized and their inhibitory activities were evaluated against wild-type and multidrug resistant HIV-1 RTs. Adenosine β-triphosphate (1) and AZT β-triphosphate (2) completely inhibited the DNA polymerase activity of wild type, the NRTI multi resistant, and non-nucleoside RT inhibitors (NNRTI) resistant HIV-1 RT at 10 nM, 10 μM, and 100 μM, respectively.

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Synthesis of nucleoside 5′-O-α,β-methylene-β-triphosphates and evaluation of their potency towards inhibition of HIV-1 reverse transcriptase

Cited by 7 publications

References 33 publications

Solid‐Phase Synthesis of (Poly)phosphorylated Nucleosides and Conjugates

Solid‐Phase Synthesis of (Poly)phosphorylated Nucleosides and Conjugates

Synthesis of β-triphosphotriester pronucleotides

Inhibition of multi-drug resistant HIV-1 reverse transcriptase by nucleoside β-triphosphates

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