First synthesis of fully modified 4'-selenoRNA and 2'-OMe-4'-selenoRNA based on the mechanistic considerations of an unexpected strand break

Noriko Tarashima; Koya Hayashi; Maki Terasaki; Hirotsugu Taniike; Yusuke Inagaki; Kenji Hirose; Kazuhiro Furukawa; Akira Matsuda; Noriaki Minakawa

doi:10.1021/ol502077h

First synthesis of fully modified 4'-selenoRNA and 2'-OMe-4'-selenoRNA based on the mechanistic considerations of an unexpected strand break

Org Lett. 2014 Sep 19;16(18):4710-3. doi: 10.1021/ol502077h. Epub 2014 Sep 2.

Authors

Noriko Tarashima¹, Koya Hayashi, Maki Terasaki, Hirotsugu Taniike, Yusuke Inagaki, Kenji Hirose, Kazuhiro Furukawa, Akira Matsuda, Noriaki Minakawa

Affiliation

¹ Graduate School of Pharmaceutical Sciences, The University of Tokushima , Shomachi 1-78-1, Tokushima 770-8505, Japan.

PMID: 25181546
DOI: 10.1021/ol502077h

Abstract

This study investigated oligonucleotide (ON) synthesis containing 4'-selenoribonucleoside(s) under standard phosphoramidite conditions. Careful operation using a manual ON synthetic system revealed that an unexpected strand break occurred to afford a C2-symmetric homodimer as a byproduct. In addition, this side reaction occurred during I2 oxidation. On the basis of these findings, the first synthesis of fully modified 4'-selenoRNA and 2'-OMe-4'-selenoRNA was achieved using tert-butyl hydroperoxide (TBHP) as the alternative oxidant.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Molecular Structure
Oligonucleotides / chemical synthesis*
Oligonucleotides / chemistry
Organometallic Compounds / chemical synthesis*
Organometallic Compounds / chemistry
Oxidants / chemistry
Oxidation-Reduction
RNA / chemistry*
Selenium / chemistry*
tert-Butylhydroperoxide / chemistry*

Substances

Oligonucleotides
Organometallic Compounds
Oxidants
RNA
tert-Butylhydroperoxide
Selenium