Solid-phase synthesis of oligouridine boranophosphates using the H-boranophosphonate method with 2′-O-(2-cyanoethoxymethyl) protection. (21st December 2021)

• Record Type: Journal Article
• Authors: Matsuda, Hiromasa; Ito, Hiroaki; Nukaga, Yohei; Uehara, Sho; Sato, Kazuki; Hara, Rintaro Iwata; Wada, Takeshi
• Is Part Of: Tetrahedron letters. Volume 87(2021)
• Publication Date: 2021-12-21
• Subjects: Boranophosphate RNA -- H-Boranophosphonate method -- Solid-phase synthesis -- 2-Cyanoethoxymethyl; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2021.153526
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: 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.