Automated Solid-Phase Synthesis of RNA Oligonucleotides Containing a Nonbridging Phosphorodithioate Linkage via Phosphorothioamidites

This work describes a general method for the synthesis of oligoribonucleotides containing a site-specific nonbridging phosphorodithioate linkage via automated solid-phase synthesis using 5′-<i>O</i>-DMTr-2′-<i>O</i>-TBS-ribonucleoside 3′-<i>N</i>,<i>N</i>-dimethyl-<i>S</i>-(2,4-dichlorobenzyl) phosphorothioamidites (<b>2a</b>–<b>2d</b>). The 3′-phosphorothioamidites (<b>2a</b>–<b>2d</b>) can be conveniently prepared in good yields (86–99%) via a one-pot reaction from the corresponding 5′-<i>O</i>-DMTr-2′-<i>O</i>-TBS-ribonucleosides (<b>1a</b>–<b>1d</b>)