Synthesis of 4′‐Selenoribonucleosides, the Building Blocks of 4′‐SelenoRNA, Using a Hypervalent Iodine

Abstract

Herein is described a detailed protocol for the synthesis of 4'-selenoribonucleoside derivatives that involves the use of a hypervalent iodine species. These derivatives are versatile units for the preparation of 4'-selenoRNA. Large-scale synthesis of a 4-selenosugar starting from D-ribose is achieved in eight steps, including a final chromatographic purification. The resulting 4-selenosugar is then subjected to the one-pot Pummerer-like reaction using hypervalent iodine in the presence of silylated nucleobases. The reaction with silylated uracil affords the desired 4'-selenouridine derivatives with excellent β-selectivity and in good yield. Conversely, when purine nucleobases are used in the Pummerer-like reaction, N7 4'-selenoribonucleoside isomers are obtained alongside the desired N9 isomers. However, the undesired N7 isomers can be converted to the desired N9 ones under acidic conditions. © 2017 by John Wiley & Sons, Inc.

Synthesis of 4′‐Thiomodified c‐di‐AMP Analogs

“…The syntheses of dimesylate 3 from D ‐ribose requires an additional 3 weeks. (Saito‐Tarashima et al., 2017). The synthesis of c‐di‐4′‐thioAMP ( 1 ) and cAMP–4′‐thioAMP ( 2 ) from 13 and 14 , respectively, each requires 5 days.…”

“…We have previously reported a protocol for synthesizing 4 -selenonucleosides via a Pummerer-like reaction using hypervalent iodine in combination with a 4-selenosugar and appropriate nucleobases (Saito-Tarashima et al, 2017). The 4 -thioadenosine monomers 13 and 14, which are the synthetic substrates for compounds 1 and 2, can be prepared by a similar procedure (Fig.…”

“…2). In short, dimesylate 3, which is prepared from D-ribose in seven steps (Saito-Tarashima et al, 2017), is heated in EtOH in the presence of NaSH to afford the desired 4-thiosugar 4. The 4-thiosugar 4 is then subjected to a Pummerer-like reaction using hypervalent iodine with 6-chloropurine to give the desired N 9 isomer 6 with the undesired N 7 isomer 5 (undesired N 7 isomer 5 can be isomerized to desired N 9 isomer 6).…”