Synthesis of Bicyclic 2′-Deoxynucleosides with α-l-<i>ribo</i>- and β-d-<i>xylo</i>-Configurations and Restricted <i>S</i>- and <i>N</i>-Type Conformations

Two bicyclic 2′-deoxynucleoside analogues are synthesized in 12 steps each from thymidine. With a six-membered ring fused to the C3′−C4′ bond and an α-l-ribo- and a β-d-xylo-configuration, these are conformationally restricted in an S- and an N-type conformation, respectively. The constitutions were proven by X-ray crystallography. The β-d-xylo-configured analogue is successfully converted to a 3′-phosphoramidite and incorporated into oligodeoxynucleotides, which are found to hybridize to DNA and RNA complements with decreased affinity.