A highly efficient procedure for the oxidation of the 5'-position of adenosine analogues

Halligan, Kathleen M.; Nair, Vasu

doi:10.3998/ark.5550190.0007.211

Cited by 3 publications

(1 citation statement)

References 14 publications

(14 reference statements)

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“…41,42 Here, we describe an improved organomagnesium procedure for the synthesis of a variety of 5′-C-methyl pyrimidine nucleosides with different 2′-substituents and simple silica gel column chromatography and crystallization techniques for complete separation of the stereoisomeric products (Scheme 1). Dess−Martin oxidation 33,52 of 3′-O-TBS-protected nucleosides 1a−d afforded unstable aldehydes 2a−d that tend to form hydrates, cyclic products, and oligomers 41,44,52,53 and also can potentially undergo epimerization at the 4′-position. 43 The aldehydes 2a−d constituted 60−70% of the crude mixtures as determined by 1 H NMR.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Structural Basis of Duplex Thermodynamic Stability and Enhanced Nuclease Resistance of 5′-C-Methyl Pyrimidine-Modified Oligonucleotides

et al. 2016

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Although judicious use of chemical modifications has contributed to the success of nucleic acid therapeutics, poor systemic stability remains a major hurdle. The introduction of functional groups around the phosphate backbone can enhance the nuclease resistance of oligonucleotides (ONs). Here, we report the synthesis of enantiomerically pure (R)- and (S)-5'-C-methyl (C5'-Me) substituted nucleosides and their incorporation into ONs. These modifications generally resulted in a decrease in thermal stability of oligonucleotide (ON) duplexes in a manner dependent on the stereoconfiguration at C5' with greater destabilization characteristic of (R)-epimers. Enhanced stability against snake venom phosphodiesterase resulted from modification of the 3'-end of an ON with either (R)- or (S)-C5'-Me nucleotides. The (S)-isomers with different 2'-substituents provided greater resistance against 3'-exonucleases than the corresponding (R)-isomers. Crystal structure analyses of RNA octamers with (R)- or (S)-5'-C-methyl-2'-deoxy-2'-fluorouridine [(R)- or (S)-C5'-Me-2'-FU, respectively] revealed that the stereochemical orientation of the C5'-Me and the steric effects that emanate from the alkyl substitution are the dominant determinants of thermal stability and are likely molecular origins of resistance against nucleases. X-ray and NMR structural analyses showed that the (S)-C5'-Me epimers are spatially and structurally more similar to their natural 5' nonmethylated counterparts than the corresponding (R)-epimers.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Structural Basis of Duplex Thermodynamic Stability and Enhanced Nuclease Resistance of 5′-C-Methyl Pyrimidine-Modified Oligonucleotides

et al. 2016

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Exploration of the molecular architecture of the orthosteric binding site in the α4β2 nicotinic acetylcholine receptor with analogs of 3-(dimethylamino)butyl dimethylcarbamate (DMABC) and 1-(pyridin-3-yl)-1,4-diazepane

Bach

Jensen

Petersen

et al. 2015

European Journal of Medicinal Chemistry

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Cytostatic and Antiviral 6-Arylpurine Ribonucleosides VIII. Synthesis and Evaluation of 6-Substituted Purine 3'-Deoxyribonucleosides

Hocek

Šilhár

Pohl

2006

Collect. Czech. Chem. Commun.

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A series of purine 3'-deoxyribonucleosides bearing diverse C-substituents (alkyl, aryl, hetaryl or hydroxymethyl) in the position 6 was prepared by Pd-catalyzed cross-coupling reactions of 6-iodo-9-[2,5-bis-O-(tert-butyldimethylsilyl)-3-deoxy-β-D-ribofuranosyl]purine with the corresponding organometallics followed by deprotection by (HF)3·Et3N. None of the title 3'-deoxyribonucleoside showed any cytostatic activity or anti-HCV effect in replicon assay.

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A highly efficient procedure for the oxidation of the 5'-position of adenosine analogues

Cited by 3 publications

References 14 publications

Structural Basis of Duplex Thermodynamic Stability and Enhanced Nuclease Resistance of 5′-C-Methyl Pyrimidine-Modified Oligonucleotides

Structural Basis of Duplex Thermodynamic Stability and Enhanced Nuclease Resistance of 5′-C-Methyl Pyrimidine-Modified Oligonucleotides

Exploration of the molecular architecture of the orthosteric binding site in the α4β2 nicotinic acetylcholine receptor with analogs of 3-(dimethylamino)butyl dimethylcarbamate (DMABC) and 1-(pyridin-3-yl)-1,4-diazepane

Cytostatic and Antiviral 6-Arylpurine Ribonucleosides VIII. Synthesis and Evaluation of 6-Substituted Purine 3'-Deoxyribonucleosides

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