Design and Synthesis of Triazole-Linked xylo-Nucleoside Dimers

Three triazole-linked nonionic xylo-nucleoside dimers T(L)-t-T(xL), T(L)-t-A(BzxL) and T(L)-t-C(BzxL) have been synthesized for the first time by Cu(I) catalyzed azide-alkyne [3 + 2] cycloaddition reaction (CuAAC) of 1-(3'-azido-3'-deoxy-2'-O,4'-C-methylene-β-D-ribo-furanosyl)thymine with different alkynes, i.e., 1-(5'-deoxy-5'-C-ethynyl-2'-O,4'-C-methylene-β-D-xylofuranosyl)thymine, 9-(5'-deoxy-5'-C-ethynyl-2'-O,4'-C-methylene-β-D-xylo-furanosyl)-N6-benzoyladenine and 1-(5'-deoxy-5'-C-ethynyl-2'-O,4'-C-methylene-β-D-xylofuranosyl)-N4-benzoylcytosine in 90%-92% yields. Among the two Cu(I) reagents, CuSO4.5H2O-sodium ascorbate in THF:(t)BuOH:H2O (1:1:1) and CuBr.SMe2 in THF used for cycloaddition (click) reaction, the former one was found to be better yielding than the latter one.