Phosphoramidites for synthetic rna in the reverse direction, efficient rna synthesis and convenient introduction of 3'-end ligands, chromophores and modifications of synthetic rna

Abstract

The present invention provides building blocks and methods for synthesizing very pure RNA in a form that can efficiently be modified at the 3' end. Reverse RNA monomer phosphoramidites have been developed for RNA synthesis in 5′→3′ direction, leading to very clean oligo synthesis that allows for the introduction of various modifications at the 3′-end cleanly and efficiently. Higher coupling efficiency per step have been observed during automated oligo synthesis with the reverse RNA amidites disclosed herein, resulting in a greater ability to achieve higher purity and produce very long oligonucleotides. The use of the reverse RNA phosphoramidites in the synthetic process of this invention leads to oligonucleotides free of N+1 species.