6-Azauracil or 8-aza-7-deazaadenine nucleosides and oligonucleotides: the effect of 2'-fluoro substituents and nucleobase nitrogens on conformation and base pairing.
The stereoselective syntheses of 6-azauracil- and 8-aza-7-deazaadenine 2'-deoxy-2'-fluoro-beta-d-arabinofuranosides and employing nucleobase anion glycosylation with 3,5-di-O-benzoyl-2-deoxy-2-fluoro-alpha-d-arabinofuranosyl bromide as the sugar component are described; the 6-azauracil 2'-deoxy-2'-fluoro-beta-d-ribofuranoside was prepared from 6-azauridine via the 2,2'-anhydro intermediate and transformation of the sugar with DAST. Compounds show a preferred N-conformer population (100% N for , and 78% N for ) 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 and were synthesized using the phosphoramidites and . 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 shows an unfavourable effect on duplex stability, while oligonucleotide duplexes containing the 8-aza-7-deazaadenine-2'-deoxy-2'-fluoroarabinonucleoside were as stable as those incorporating dA or 8-aza-7-deaza-2'-deoxyadenosine .
Seela
Frank
F
Laboratory of Bioorganic Chemistry and Chemical Biology, Center for Nanotechnology, Heisenbergstrasse 11, 48149 Münster, Germany. frank.seela@uni-muenster.de
Chittepu
Padmaja
P
D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry; D020029:Base Pairing; D001483:Base Sequence; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000235:genetics; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D009584:Nitrogen / Q000737:chemistry*; D009691:Nucleic Acid Denaturation; D009705:Nucleosides / Q000737:chemistry*; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000235:genetics; D009943:Organophosphorus Compounds / Q000138:chemical synthesis; D012313:RNA / Q000737:chemistry / Q000235:genetics; D013237:Stereoisomerism; D044366:Transition Temperature; D014498:Uracil / Q000031:analogs & derivatives* / Q000737:chemistry
D009705:Nucleosides; D009841:Oligonucleotides; D009943:Organophosphorus Compounds; C434331:phosphoramidite; C414764:8-aza-7-deazaadenine; D014498:Uracil; D012313:RNA; D004247:DNA; C100248:azauracil; D000225:Adenine; D009584:Nitrogen