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Synthesis of a Novel Bicyclic Nucleoside Restricted to an S-Type Conformation and Initial Evaluation of Its Hybridization Properties When Incorporated into Oligodeoxynucleotides

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journal contribution
posted on 04.07.2001, 00:00 by Lisbet Kværnø, Richard H. Wightman, Jesper Wengel
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-β-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 °C per modification toward complementary DNA and RNA, respectively.