Although model deprotection studies using compounds 5a-b indicated that the SoM group was suitable for amino protection for sensitive RNA synthesis, the efficiency of deprotection of SoM groups on actual RNA molecules was still uncertain. Therefore, once we synthesized the phosphoramidite 1a and the linker 1f, we decided to synthesize the 8-mer RNA 19a (Figure ) before synthesizing phosphoramidites 1b-c. If SoM were found not ideal, alternative groups would have to be investigated. Because the fully protected RNA after solid phase synthesis was in the form of 2 and linker cleavage was to be carried out using fluoride (Scheme 1), the solid support had to be exposed to fluoride during cleavage. To avoid potential problems caused by the reactions between fluoride and controlled pore glass (CPG), the commercially available highly cross-linked polystyrene resin based solid support 1-dimethoxytrityloxy-2-O-dichloroacetyl-propyl-3-N-ureayl-polystyrene was used as the solid support. In principle, any support that is inert toward fluoride as well as other ingredients in the deprotection reagent with a hydroxy group or DMTr-protected hydroxy group can be used as the support.