Practical and Reliable Synthesis of 1,2-Dideoxy-d-ribofuranose and its Application in RNAi Studies

Abstract

We developed a practical and reliable method for synthesizing an abasic deoxyribonucleoside, 1,2-dideoxy-d-ribofuranose (dR(H)) via elimination of nucleobase from thymidine. To synthesize oligonucleotides bearing dR(H) by the standard phosphoramidite solid-phase method, dR(H) was converted to the corresponding phosphoramidite derivative and linked to a solid support (controlled pore glass resin). Chemically modified small interfering RNAs (siRNAs) possessing dR(H) at their 3'-overhang regions were synthesized. Introducing dR(H) to the 3'-end of the antisense strand of siRNA reduced its knockdown effect.

Exploring PAZ/3′-overhang interaction to improve siRNA specificity. A combined experimental and modeling study

“… 47 , 59 , 60 Abasic nucleotides have been incorporated in siRNA molecules both in external and internal positions and, contradictorily, shown to be detrimental or beneficial for siRNA potency. 9 , 61 , 62 Interestingly, the presence of this analogue at some of the seed region positions prevents miRNA-like off-target effects. 9 , 62 The study of bulky derivatives is also documented, but the compound synthesized in this work was never studied before in detail.…”

Synthesis and Photophysical Studies on N1‐(Coumarin‐4′′′‐yl)‐C4‐(2′,3′‐dideoxyuridin‐3′‐yl/3′‐deoxythymidin‐3′‐yl)‐oxymethyl‐1,2,3‐triazoles

“…[29] Thus, the click reaction of the 4-azidocoumarin ( 2 , respectively. [30] The structures of all synthesized compounds 2 a-f, 5 a & 5 b, 6 a-f, 7 a-f, 8 a-f and 9 a-f were confirmed on the basis of their spectral data analysis (IR, 1 H NMR, 13 C NMR, 1 H-1 H COSY, 1 H- 13 C HETCOR, DEPT-135 NMR spectra and HRMS spectral data analysis. The structures of known compounds 2 a, 2 c and 4 a, 4 b were further confirmed by comparison of their spectral data with those reported in the literature.…”

“…Thus, the click reaction of the 4‐azidocoumarin ( 2 a ), 4‐azido‐2 H ‐benzo[ h ]coumarin ( 2 b ), 6‐bromo‐4‐azidocoumarin ( 2 c ), 7‐( N,N ‐dimethylamino)‐4‐azidocoumarin ( 2 d ), 6,7,8‐( N,N ‐dibutylene‐ N ‐methyleneamino)‐4‐azidocoumarin ( 2 e ), 7‐(pyrrolidine)‐4‐azidocoumarin ( 2 f ) with the silylated 3’‐ O ‐propynylmethylpyrimidin nucleoside precursors 5 a/5 b was carried in t BuOH at 80 °C to afford protected coumarin‐triazolylmethyl nucleoside conjugates 6 a – f in 70–82 % and 7 a – f in 68–82 % yields. The deprotection of the silylated coumarin‐triazolylmethyl nucleoside conjugates 6 a – f and 7 a – f was carried out with TBAB in THF at room temperature to afford desired N 1 ‐(coumarin‐4′′′‐yl)‐ C 4 ‐(2′,3′‐di‐deoxyuridin‐3′‐yl)‐oxymethyl‐1,2,3‐triazoles 8 a – f in 81–87 % yield and N 1 ‐(coumarin‐4′′′‐yl)‐ C 4 ‐(3′‐deoxythymin‐3′‐yl)‐oxymethyl‐1,2,3‐triazoles 9 a – f in 84–91 % yield (Scheme 2), respectively [30] …”

Chemical Modification of the 3′-Dangling End of Small Interfering RNAs Such as siRNAs and miRNAs: The Development of miRNA Replacement Therapy

“…To synthesize oligonucleotides bearing the 1,2-dideoxyribofuranose by the standard phosphoramidite solid-phase method, the dideoxyribofuranose was converted to the corresponding phosphoramidite derivative and its CPG-resin. Introducing the dideoxyribofuranose to the 3′-end of the antisense strand of siRNA (8) reduced its knockdown effect [13].…”