Synthesis of the Methyl Analog of 2′- O,4′- C-Ethylene-Bridged 5-Methyluridine via Intramolecular Radical Cyclization and Properties of Modified Oligonucleotides

Abstract

The synthesis of 6′S-Me-2′-O,4′-C-ethylene-bridged 5-methyluridine (6′S-Me-ENA-T) was achieved using visible light-mediated stereoselective radical cyclization as a key step. This is the first example of a method for constructing a 2′,4′-bridged structure from a 4′-carbon radical intermediate. The 6′S-Me-ENA-T monomer was successfully incorporated into oligonucleotides, and their properties were examined. The oligonucleotides containing 6′S-Me-ENA-T exhibited a highly selective hybridization affinity toward single-stranded RNA and an excellent enzymatic stability, compared to the corresponding LNA- and ENA-modified oligonucleotides.