Synthesis of 7’‐Substituted 2’‐O‐4’‐C‐Ethylene Bridged Nucleic Acid (ENA)‐Thymidine Monomers

Abstract

AbstractDerivatives of 2’‐O‐4’‐C‐Ethylene‐bridged Nucleic Acid (ENA) monomer, a nucleoside used in the preparation of antisense modified oligonucleotides and featuring an alkyl group in position 7’, are stereoselectively produced in nine steps from commercially available 3‐O‐benzyl‐4‐(hydroxymethyl)‐1,2‐O‐isopropylidene‐alpha‐D‐ribofuranose. The synthesis relies on a sequence of reactions involving a Tebbe olefination, a key ring‐closing metathesis, and an enol ether reduction.