Solid-phase synthesis of oligouridine boranophosphates using the H-boranophosphonate method with 2′-O-(2-cyanoethoxymethyl) protection

Abstract

Oligonucleotides with the boranophosphate (PB) modification attract much attention as promising therapeutic agents. The PB modification is useful for the development of small interfering RNAs (siRNAs); however, the chemical synthesis of long PB-oligoribonucleotides has not been achieved to date. This study reports the solid-phase synthesis of oligouridine boranophosphates using the H-boranophosphonate monomer with a 2′-O-(2-cyanoethoxymethyl) (CEM) protecting group. As a result of various investigations, the conditions for the solid-phase synthesis and removal of 2′-O-CEM groups were optimized. Notably, we found that the counter cation of a boranophosphate moiety plays an important role in the deprotection step of 2′-O-CEM groups. Finally, oligouridine boranophosphates were successfully obtained up to a dodecamer.