Chemical synthesis of oligonucleotides. 3: Synthesis and characterization of N, O-protected ribophosphoesters for applications in RNA synthesis

Abstract

The chemical synthesis of RNA, in contrast to that of DNA, poses problems due to fi) additional requirement of 2'-hydroxyl protection of the ribose moieties, and (ii) high lability of inter-ribophosphate bonds. Herein we report the synthesis and characterisation of N, O-protected ribophosphoesters 1 which are key monomeric derivatives in phosphotriester methodology for RNA synthesis. Both the isomeric 2' and 3'-O-phosphates have been obtained and characterised. The utility of the t-butyl dimethylsilyl group for 2'-hydroxyl protection in the phosphotriester method is demonstrated by the synthesis of r(AUAU),r(UAUA) and r(CACA).