Synthesis of bicyclic 2'-deoxynucleosides with alpha-L-ribo- and beta-D-xylo-configurations and restricted S- and N-type conformations

Abstract

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 alpha-L-ribo- and a beta-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 beta-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.