New and convenient protection system for pseudouridine, highly suitable for solid-phase oligoribonucleotide synthesis

Abstract

The pivaloyloxymethyl (Pom) group has been used simultaneously to protect both nitrogens in the uracil ring system of pseudouridine. This enabled the synthesis of a 2′-O-[1-(2-fluorophenyl)-4-methoxypiperidin-4-yl]-protected (Fpmp protected) pseudouridine building block suitable for solidphase oligoribonucleotide synthesis by the phosphoramidite method as well as a useful 2′-O-methylpseudouridine building block. Both compounds were incorporated in high yield into synthetic oligonucleotides, the Pom groups being cleaved during an extended deblock with ammonia.