Ralph Steffans, C. Leumann
Dec 15, 1997
Citations
0
Influential Citations
33
Citations
Journal
Helvetica Chimica Acta
Abstract
The synthesis of the tricyclo-deoxynucleoside analogs 1 and 2 and of the corresponding cyanoethyl phosphoramidite building blocks 16 and 21 for oligonucleotide synthesis is described. These tricyclic deoxynucleoside analogs differ from the recently introduced bicyclo-deoxynucleosides by an additional cyclopropane unit joined to the centers C(5′) and C(6′) of the latter (se Fig. 1), and thus represent a further member of the class of nucleoside analogs with constraint conformational flexibility. The synthesis of the tricyclo-deoxynucleoside was achieved by a diastereoselective carbene addition to the enantiomerically pure silyl enol either 8/9 and a Vorbruggen condensation of the tricyclic carbohydrate unit 10/11 with in situ persilylated thymine and N6-benzoyladenine. Selective tritylation of the tertiary OHC(5′) and phosphinylation of OHC(3′) of 1 and 2 afforded the corresponding phosphoramidites 16 and 21. The ‘exo’-configuration of the newly introduced cyclopropane ring was confirmed by 1H-NMR-NOE spectroscoy. The α-D- and β-D-configuration at C(1′) of the nucleoside analogs 1 and 14 (2 and 19, resp.) was assigned by 1H-NMR-NOE spectroscopy and NOESY. Modeling studies of the β-D-anomeric nucleoside analog 1 indicate a preference for the 2′-endo-conformation of the furanose ring and a partial correction of the torsion angle γ to the anti-clinal range compared to bicyclo-deoxynucleosides.