First Synthesis of Fully Modified 4′-SelenoRNA and 2′-OMe-4′-selenoRNA Based on the Mechanistic Considerations of an Unexpected Strand Break

• Published in: Organic letters Vol. 16; no. 18; pp. 4710 - 4713
• Main Authors: Tarashima, Noriko, Hayashi, Koya, Terasaki, Maki, Taniike, Hirotsugu, Inagaki, Yusuke, Hirose, Kenji, Furukawa, Kazuhiro, Matsuda, Akira, Minakawa, Noriaki
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 19-09-2014
• Subjects: 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
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/ol502077h

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.