Efficient Divergent Synthesis of 2′-O,4′-C-Ethylene-Bridged Nucleic Acid (ENA) Phosphoramidites

2′-O,4′-C-Ethylene-bridged nucleic acid (ENA) phosphoramidites are highly promising modified nucleic acid monomers discovered by Daiichi Sankyo. To increase the productivity of manufacturing, we have developed a highly efficient synthetic method for ENA phosphoramidites. The basic concept of the new synthetic route is “divergent synthesis” for the preparation of four types of monomers such as A, G, C, and T. We applied stereoselective glycosylation reactions without utilizing neighboring group participation to set a common intermediate in the downstream of the route.