title: Synthesis of a novel bicyclic nucleoside restricted to an S-type conformation and initial evaluation of its hybridization properties when incorporated into oligodeoxynucleotides.
abstract: The phosphoramidite (1S,3R,4S)-3-(2-cyanoethoxy(diisopropylamino)phosphinoxymethyl)-5-N-(4-monomethoxytrityl)-1-(uracil-1-yl)-5-aza-2-oxabicyclo[2.2.1]heptane 18 of a novel bicyclic nucleoside structure was synthesized from the known 1-(3'-deoxy-beta-D-psicofuranosyl)uracil 3. Conformational analysis of its structure verified its expected S-type furanose conformation, and the secondary amino group in the 4'-position allowed for incorporation into oligonucleotides using 5' --> 3' directed oligonucleotide synthesis as previously described for phosphoramidates. Thermal denaturation studies showed rather large decreases in duplex stabilities of -4.3 and -2.7 degrees C per modification toward complementary DNA and RNA, respectively.
authors.affiliation: Center for Synthetic Bioorganic Chemistry, Department of Chemistry, University of Copenhagen, Universitetsparken 5, DK-2100 Copenhagen, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Kvaernø
authors.forename: R H
authors.initials: RH
authors.lastname: Wightman
authors.forename: J
authors.initials: J
authors.lastname: Wengel
mesh_terms: D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis*; D004247:DNA / Q000737:chemistry; D007202:Indicators and Reagents; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D009841:Oligonucleotides / Q000138:chemical synthesis*; D012313:RNA / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013696:Temperature; D014498:Uracil / Q000031:analogs & derivatives / Q000138:chemical synthesis*
chemical_list: C433387:3-(2-cyanoethoxy(diisopropylamino)phosphinoxymethyl)-5-N-(4-monomethoxytrityl)-1-(uracil-1-yl)-5-aza-2-oxabicyclo(2.2.1)heptane; D001643:Bridged Bicyclo Compounds; D007202:Indicators and Reagents; D009841:Oligonucleotides; D014498:Uracil; D012313:RNA; D004247:DNA