Design and Synthesis of Triazole-Linkedxylo-Nucleoside Dimers

Abstract

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.

Cu-Catalyzed Click Reaction in Carbohydrate Chemistry

“…404 Very recently, Prasad et al synthesized an interesting triazole-linked nonionic xylo nucleoside dimer (298) including T L -t-T xL , T L -t-A BzxL , and T L -t-C BzxL using the CuAAC reaction of azide 296 and alkyne 297 (Scheme 84). 405 Nucleic acid conjugates have widespread applications in biomedicine, such as in diagnostics and also in therapy, especially for cancer treatment. tag.…”

Multicomponent Click Reaction: An Indispensable Tool for Easy Access of Functionalized 1,2,3‐Triazoles

“…[116] By coupling azide and alkyne via a 1,2,3-triazole linker under standard CuAAC conditions, this modular CuAAC tool could be used to generate high yields of non-ionic xylo-nucleoside dimers. [117] It's interesting to note that CuAAC Click conjugation of two complementary oligonucleotides gave massive dsDNA catenanes that were composed of six helical turns, with TÀ T mismatches on either side of ten base pairs. Two strands that had been labelled with a 5'-alkyne and a 3'-azide were used step-wise to provide the dsDNA catenane macrostructure; the non-templated CuAAC coupling of the first oligonucleotide was first cyclized via intramolecular fashion, which was then used as a template for the second oligonucleotide's click ligation and cyclization.…”