Synthesis of 3-deaza-3-nitro-2′-deoxyadenosine

Crey-Desbiolles, Caroline; Kotera, Mitsuharu

doi:10.1016/j.bmc.2005.10.040

Cited by 15 publications

(21 citation statements)

References 26 publications

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“…Deprotection of 16 under basic conditions afforded 4 (Scheme 1). The readily prepared nucleobase 4-chloro-1 H -imidazo[4,5- c ]pyridine27 was used as an intermediate to yield 3-deaza-6-methyl-9-β-D-ribofuranosylpurine ( 5 ), which was synthesized by known methods 28…”

Section: Chemical Synthesismentioning

confidence: 99%

Synthesis of a 6-Methyl-7-deaza Analogue of Adenosine That Potently Inhibits Replication of Polio and Dengue Viruses

Smidansky

et al. 2010

J. Med. Chem.

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Bioisosteric deaza analogues of 6-methyl-9-β-D-ribofuranosylpurine, a hydrophobic analogue of adenosine, were synthesized and evaluated for antiviral activity. Whereas the 1-deaza and 3-deaza analogues were essentially inactive in plaque assays of infectivity, a novel 7-deaza-6-methyl-9-β-D-ribofuranosylpurine analogue, structurally related to the natural product tubercidin, potently inhibited replication of poliovirus (PV) in HeLa cells (IC 50 = 11 nM) and dengue virus (DENV) in Vero cells (IC 50 = 62 nM). Selectivity against PV over cytotoxic effects to HeLa cells was >100-fold after incubation for 7 h. Mechanistic studies of the 5'-triphosphate of 7-deaza-6-methyl-9-β-D-ribofuranosylpurine revealed that this compound is an efficient substrate of PV RNA-dependent RNA polymerase (RdRP) and is incorporated into RNA mimicking both ATP and GTP.

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Section: Chemical Synthesismentioning

confidence: 99%

Synthesis of a 6-Methyl-7-deaza Analogue of Adenosine That Potently Inhibits Replication of Polio and Dengue Viruses

Smidansky

et al. 2010

J. Med. Chem.

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“…En route to 3-deazaadenine analogues of purines, we first investigated the reactivity of the readily available 3-deazaadenine 1 ( Scheme 1 ) in cross-coupling reactions. 15 In direct attempts to utilize it as a cross-coupling partner, we were able to obtain the 3-iodo-3-deazaadenine 2 and observe its acceptable reactivity under Suzuki cross-coupling conditions using the Pd(OAc) 2 /3,3′,3″-phosphanetriyltris(benzenesulfonic acid) trisodium salt (TPPTS) catalyst system, a general method developed for aqueous coupling reactions of halogenated purine/pyrimidine nucleobases and nucleosides. 4 , 26 , 28 The reactions of 2 with phenylboronic acid and trans -2-phenylvinylboronic acid afforded compounds 3a and 3b with 65 and 58% yield, respectively ( Scheme 1 ).…”

Section: Results and Discussionmentioning

confidence: 99%

“…A TLC analysis indicated that an extensive deglycosylation occurred, indicating the instability of the compound, which may be ascribed to the electronic character of phenyl group at the position 3, as suggested by other reports. 15 Deglycosylation was also observed to occur upon mild heating of the TLC plate to remove pyridine before analysis.…”

Section: Experimental Sectionmentioning

confidence: 99%

“…Several modifications, such as 3-methyl, the related protected 3-hydroxymethyl, and methylenethiol or nitro groups were reported. 12 − 15 3-Deaza-3-fluoroadenosines had to be synthesized stepwise, but other 3-halo derivatives could also be obtained through direct halogenation of the nonsubstituted 3-deazaadenosines. 16 − 22 The use of cross-coupling reactions in C3 modification of purines is, however, limited.…”

Section: Introductionmentioning

confidence: 99%

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Tuning Cross-Coupling Approaches to C3 Modification of 3-Deazapurines

et al. 2017

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A general approach to C3 modification of purine scaffold through various types of cross-coupling reactions has been established. Tuning substrate electronics and reaction conditions resulted in the development of highly efficient sp2–sp, sp2–sp2, and sp2–sp3 cross-coupling conditions for modification of 3-deazaadenine to access C3-modified adenine and hypoxanthine scaffolds. The optimized methodologies to access the corresponding 3-deazaadenosine phosphoramidites for solid-phase DNA synthesis have been demonstrated.

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“…Previously, we described the synthesis of d(3-NiA) and its incorporation in oligonucleotides as a phosphoramidite monomer (24,25). Photocleavage of DNA containing the modified 3-NiA base was shown to be quantitative and rapid, both in single- and double-strand DNA (22).…”

Section: Introductionmentioning

confidence: 99%

Chemical synthesis, DNA incorporation and biological study of a new photocleavable 2'-deoxyadenosine mimic

Berthet

Crey-Desbiolles

Kotera

et al. 2009

Nucleic Acids Research

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The phototriggered cleavage of chemical bonds has found numerous applications in biology, particularly in the field of gene sequencing through photoinduced DNA strand scission. However, only a small number of modified nucleosides that are able to cleave DNA at selected positions have been reported in the literature. Herein, we show that a new photoactivable deoxyadenosine analogue, 3-nitro-3-deaza-2′-deoxyadenosine (d(3-NiA)), was able to induce DNA backbone breakage upon irradiation (λ > 320 nm). The d(3-NiA) nucleoside was chemically incorporated at desired positions into 40-mer oligonucleotides as a phosphoramidite monomer and subsequent hybridization studies confirmed that the resulting modified duplexes display a behaviour that is close to that of the related natural sequence. Enzymatic action of the Klenow fragment exonuclease free revealed the preferential incorporation of dAMP opposite the 3-NiA base. On the other hand, incorporation of the analogous 3-NiA triphosphate to a primer revealed high enzyme efficiency and selectivity for insertion opposite thymine. Furthermore, only the enzymatically synthesized base pair 3-NiA:T was a substrate for further extension by the enzyme. All the hybridization and enzymatic data indicate that this new photoactivable 3-NiA triphosphate can be considered as a photochemically cleavable dATP analogue.

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Synthesis of 3-deaza-3-nitro-2′-deoxyadenosine

Cited by 15 publications

References 26 publications

Synthesis of a 6-Methyl-7-deaza Analogue of Adenosine That Potently Inhibits Replication of Polio and Dengue Viruses

Synthesis of a 6-Methyl-7-deaza Analogue of Adenosine That Potently Inhibits Replication of Polio and Dengue Viruses

Tuning Cross-Coupling Approaches to C3 Modification of 3-Deazapurines

Chemical synthesis, DNA incorporation and biological study of a new photocleavable 2'-deoxyadenosine mimic

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