RNA Synthesis: phosphoramidites for RNA synthesis in the reverse direction. Highly efficient synthesis and application to convenient introduction of ligands, chromophores and modifications of synthetic RNA at the 3'-end.

Defined sequence RNA synthesis by 3'-->5' direction is now well established and currently in use for synthesis and development of vast variety of therapeutic grade RNA and Si RNA etc. A number of such synthetic RNA requires a modification or labeling of 3'- end of an oligonucleotide. The synthesis of 3'- end modified RNA requiring lipophilic, long chain ligands or chromophores, using 3' --> 5' synthesis methodology is challenging, requires corresponding solid support and generally results in low coupling efficiency and lower purity of the final oligonucleotide in general because of large amount of truncated sequences containing desired hydrophobic modification. We have approached this problem by developing reverse RNA monomer phosphoramidites for RNA synthesis in 5' --> 3'- direction. They lead to very clean oligonucleotide synthesis allowing for introduction of various modifications at the 3'- end.