Abstract: Disclosed are O-protected compounds of the formula (I): wherein B is an optionally protected nucleobase, and R1-R3 are as described herein, wherein at least one of R1-R3 is —CH2—O—N?CHR. The compounds are useful as intermediates in oligonucleotide synthesis. Also disclosed is a method of preparing the compounds from nucleosides via a process comprising conversion of a hydroxyl group to a methylthiomethoxy group, and a method of preparing oligonucleotides such as RNA starting from the compounds. The —CH2—O—N?CHR group is stable during oligonucleotide synthesis and can be easily removed after synthesis via, for example, treatment with a base.

Abstract: Disclosed are O-protected compounds of the formula (I): wherein B is an optionally protected nucleobase, and R1-R3 are as described herein, a method of preparing such compounds, and a method of preparing oligonucleotides such as RNA starting from such compounds. The O-protected compounds have one or more advantages, for example, the 2?-O-protected compound is stable during the various reaction steps involved in oligonucleotide synthesis; the protecting group can be easily removed after the synthesis of the oligonucleotide, for example, by reaction with tetrabutylammonium fluoride; and/or the O-protected groups do not generate DNA/RNA alkylating side products, which have been reported during removal of 2?-O-(2-cyanoethyl)oxymethyl or 2?-O-[2-(4-tolylsulfonyl)ethoxymethyl groups under similar conditions.