6-Azauracil or 8-aza-7-deazaadenine nucleosides and oligonucleotides: the effect of 2 `-fluoro substituents and nucleobase nitrogens on conformation and base pairing

Autor(en): Seela, Frank
Chittepu, Padmaja
Stichwörter: ACIDS; AGENTS; ANALOGS; ANTIVIRAL NUCLEOSIDES; Chemistry; Chemistry, Organic; DUPLEX STABILITY; MODIFIED DNA; PROTECTION; PYRIMIDINE NUCLEOSIDES; SUGAR CONFORMATION; URACIL
Erscheinungsdatum: 2008
Herausgeber: ROYAL SOC CHEMISTRY
Journal: ORGANIC & BIOMOLECULAR CHEMISTRY
Volumen: 6
Ausgabe: 3
Startseite: 596
Seitenende: 607
Zusammenfassung: 
The stereoselective syntheses of 6-azauracil- and 8-aza-7-deazaadenine 2'-deoxy-2'-fluoro-beta-D-arabinofurano sides 1c and 2c employing nucleobase anion glycosylation with 3,5-di-O-benzoyl-2-deoxy-2-fluoro-alpha-D-arabinofuranosyl bromide 6 as the sugar component are described; the 6-azauracil 2'-deoxy-2'-fluoro-beta-D-ribofuranoside 1d was prepared from 6-azauridine 8 via the 2,2'-anhydro intermediate 9 and transformation of the sugar with DAST. Compounds show a preferred N-conformer population (100% N for 1c, 1d and 78% N for 2c) being rather different from nucleosides not containing the combination of a fluorine atom at the 2'-position and a nitrogen next to the glycosylation site. Oligonucleotides incorporating 1c and 2c were synthesized using the phosphoramidites 3b and 4. Although the N-conformation is favoured in the series of 6-azauracil- and 8-aza-7-deazaadenine 2'-deoxy-2'-fluoroarabinonucleosides only the pyrimidine compound Ic shows an unfavourable effect on duplex stability, while oligonucleotide duplexes containing the 8-aza-7-deazaadenine-2'-deoxy-2'-fluoroarabinonucleoside 2c were as stable as those incorporating dA or 8-aza-7-deaza-2'-deoxyadenosine 2a.
ISSN: 14770520
DOI: 10.1039/b715512c

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