ChemInform Abstract: Synthesis and Antiviral Activity of Several 2,5′‐Anhydro Analogues of 3′‐Azido‐3′‐deoxythymidine, 3′‐Azido‐2′,3′‐dideoxyuridine, 3′‐Azido‐2′,3′‐dideoxy‐5‐halouridines, and 3′‐Deoxythymidine Against Human Immunodeficiency Virus and Rauscher‐Murine Leukemia Virus.

Lin, Tao; Shen, Zican; August, Elias; Brankovan, V.; Yang, Haitao; Ghazzouli, Ismail; Prusoff, William H.

doi:10.1002/chin.199002328

Cited by 2 publications

(10 citation statements)

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“…The present findings indicate that the loss of ring strain during hydrolysis of cyclic nucleosides does not increase the rate of hydrolysis contrary to what might have been expected 24,25. Reese et al 26.…”

Section: Resultscontrasting

confidence: 81%

“…Cyclonucleosides have been synthetic, structural, and biological targets for many years. − , For example, 8,5′-cycloadenosine is an inhibitor of rhodopsin kinase and the 2,5′-cylclothymidine derivatives have shown antiviral properties . The 8,5′-cyclopurine nucleosides such as 8,5′- cyclo -dG and 8,5′- cyclo -dA have been identified as the major tandem oxidative DNA damage lesions .…”

Section: Resultsmentioning

confidence: 99%

“…Cyclo-dT ( 17 ) was prepared according to a general cyclization procedure 24. To a solution of 3 (1.13 g, 2.54 mmol) in acetonitrile (70 mL) was added DBU (0.7 g, 4.6 mmol).…”

Section: Methodsmentioning

confidence: 99%

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α,β-Methylene-2′-deoxynucleoside 5′-Triphosphates as Noncleavable Substrates for DNA Polymerases: Isolation, Characterization, and Stability Studies of Novel 2′-Deoxycyclonucleosides, 3,5′-Cyclo-dG, and 2,5′-Cyclo-dT

et al. 2008

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The 2’-deoxynucleoside 5’-triphosphate (dNTP) analogs with modifications in the triphosphate chain have been used as nucleotide probes in various biochemical and structural studies. Here we report synthesis and characterization of a complete set of α,β-methylene-2’-dNTPs (α,β-m-dNTP; N = A, C, T, G, 12-15), in which the α,β-oxygen linkage of natural dNTP was replaced isosterically by a methylene group. These nucleotides were designed to be non-cleavable DNA polymerase substrates. Our synthesis process entails preparation of 2’-deoxynucleoside 5’-diphosphate precursors by nucleophilic coupling of 5’-tosyl nucleosides and methylene-diphosphate, and a subsequent enzymatic γ-phosphorylation. All four synthesized α,β-m-dNTPs were found to be potent inhibitors of polymerase β with Ki values ranging from 1-5 μM. During preparation of the dG and dT derivatives of α,β-methylene diphosphate, we isolated significant amounts of 3,5’-anhydro-2’-deoxyguanosine (cyclo-dG, 16) and 2,5’-anhydro-2’-deoxythymidine (cyclo-dT, 17), respectively. These novel 2’-deoxycyclonucleosides were formed via a base-catalyzed deprotonation of the imino proton (N1-H and N3-H), followed by an intramolecular cyclization (N3 → C5’ and O2 → C5’, respectively). In acidic solution, the cyclonucleosides underwent glycolysis at N9, followed by complete depurination at N3. In the case of cyclo-dG, there existed an equilibrium between glycolysis and deglycolysis at the glycosidic linkage prior to complete depurination. When exposed to alkaline conditions, cyclo-dG underwent an oxidative deamination at C2 to produce 3,5’-anhydro-2’-deoxyxanthosine (cyclo-dX, 19), whereas cyclo-dT was hydrolyzed exclusively to dT via cleavage at the 2,5’-ether linkage.

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Section: Resultscontrasting

confidence: 81%

Section: Resultsmentioning

confidence: 99%

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α,β-Methylene-2′-deoxynucleoside 5′-Triphosphates as Noncleavable Substrates for DNA Polymerases: Isolation, Characterization, and Stability Studies of Novel 2′-Deoxycyclonucleosides, 3,5′-Cyclo-dG, and 2,5′-Cyclo-dT

et al. 2008

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“…Treatment of 4 with the amino derivative 5 [11] in refluxing CH 2 Cl 2 with Et 3 N as a base afforded, after chromatography, 6 (58%), which gave the free nucleoside 7 (17%) on deblocking with NH 3 /MeOH at 23 • C. The low yield of 7 might be explained in term of the hydrolysis of 5 -piperazinyl-nitroimidazole group. Alternatively, AZT was converted into the 5 -O-sulphonate derivative 2 (67%) [12] by treatment with p-toluene sulphonyl chloride in pyridine at 0 • C for 8 hours. Treatment of 2 with NaSEt in DMF at 120 • C under argon afforded, after chromatography, 8 (62%).…”

Section: Resultsmentioning

confidence: 99%

“…(2). This compound was prepared from 1 as described by Lin et al [12] The product was purified by column chromatography and crystallized by EtOH to yield 2 (69%), m.p. 125-126 • C (lit.…”

Section: Generalmentioning

confidence: 99%

New AZT Analogues Having 5′-Alkylsulfonyl Groups: Synthesis and Anti-HIV Activity

Al‐Masoudi

Al‐Soud

Ali

et al. 2007

Nucleosides, Nucleotides and Nucleic Acids

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New derivatives of azidothymidine (AZT) substituted by alkyl and alkylsulphonyl groups at N-3 and C-5', respectively, have been synthesized. The new synthesized derivatives showed remarkable anti-HIV-1 and HIV-2 activity in MT-4 cells. Compounds 8 and 10 have IC(50) values of 0.83 and 0.31 microg/mL against HIV-1 with therapeutic index of 83 and 403, respectively, and IC(50) values of 0.93 and 0.29 microg/mL against HIV-2 with therapeutic index of 74 and 431, respectively. This means that compounds 8 and 10 were cytotoxic to MT-4 cells at CC(50) of 69.2 microg/mL and 125 microg/mL, respectively.

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Cited by 2 publications

References 1 publication

α,β-Methylene-2′-deoxynucleoside 5′-Triphosphates as Noncleavable Substrates for DNA Polymerases: Isolation, Characterization, and Stability Studies of Novel 2′-Deoxycyclonucleosides, 3,5′-Cyclo-dG, and 2,5′-Cyclo-dT

α,β-Methylene-2′-deoxynucleoside 5′-Triphosphates as Noncleavable Substrates for DNA Polymerases: Isolation, Characterization, and Stability Studies of Novel 2′-Deoxycyclonucleosides, 3,5′-Cyclo-dG, and 2,5′-Cyclo-dT

New AZT Analogues Having 5′-Alkylsulfonyl Groups: Synthesis and Anti-HIV Activity

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