Preparation of 2′‐O‐[(Triisopropylsilyl)oxy]methyl‐protected Ribonucleosides

Abstract

The [(triisopropylsilyl)oxy]methyl (TOM) group is a useful protecting group for the 2′‐OH of ribonucleosides to be used for oligoribonucleotide synthesis by the phosphoramidite method. It is completely stable to all reaction conditions applied during assembly and the first deprotection step. It does not interfere with the coupling reaction and leads to very good coupling yields under DNA‐coupling conditions. The final cleavage occurs quantitatively without concomitant destruction of the RNA product. This unit describes the synthesis and characterization of 2′‐O‐TOM‐5′‐O‐dimethoxytrityl‐N‐acetyl ribonucleosides in full detail. The TOM‐group is introduced via a dibutyltin dichloride‐mediated reaction into N‐acetylated, 5′‐O‐dimethoxytritylated ribonucleosides. Support protocols describe the synthesis of N‐acetylated, 5′‐O‐dimethoxytritylated adenosine and guanosine, as well as synthesis of the starting reagent [(triisopropylsilyl)oxy]methyl chloride (TOM‐Cl). Preparation of the phosphoramidites and their use in solid‐phase oligonucleotide synthesis are described elsewhere in the series.