Synthesis of selenomethylene-locked nucleic acids (SeLNA) nucleoside unit bearing an adenine base

Abstract

Synthesis of selenomethylene-locked nucleic acids nucleoside bearing an adenine base (SeLNA-A) was investigated. We first examined the stereoinversion reaction at 2′-positions of a 5′,3′-O-TIPDS-protected 4′-C-(hydroxymethyl)ribosyladenine derivative to give the corresponding arabinosyladenine. After triflation, treatment of the arabinosyladenine derivative with a mixture of selenium and sodium borohydride in ethanol managed to construct the desired SeLNA skeleton. Finally, removal of TIPDS by treating with fluoride gave the SeLNA-A nucleoside. In this study, we found the heat-labile property of SeLNA-A. It is necessary to know more precise characteristics of SeLNA to achieve its oligonucleotides synthesis.

Keywords:

• Nucleoside
• oligonucleotide
• LNA
• seleno-compound

Additional information

Funding

This work was partially supported by JSPS KAKENHI Numbers JP17K08364 and by platform project for supporting drug discovery and life science research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) from AMED under Grant Number JP19am0101099.