Second Generation Synthesis of Modified Dinucleotide Analogues Featuring a Difluorophosphin(othio)yl Linkage
Résumé
Abstract Derivatives 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.