Innovative 2'-O-Imino-2-propanoate-Protecting Group for Effective Solid-Phase Synthesis and 2'-O-Deprotection of RNA Sequences.

摘要: The implementation of protecting groups for the 2'-hydroxyl function ribonucleosides is still challenging, particularly when RNA sequences must be highest purity therapeutic applications as nucleic acid-based drugs. A 2'-hydroxyl-protecting group should optimally (i) easy to install; (ii) allow rapid and efficient incorporation 2'-O-protected into minimize, greatest extent possible, formation process-related impurities (e.g., shorter than full-length sequences) during solid-phase synthesis; (iii) completely cleaved from without production alkylating side products and/or mutagenic nucleobase adducts. reaction 2'-O-aminoribonucleosides with ethyl pyruvate results in stable 2'-O-imino-2-methyl propanoic acid esters and, subsequently, fully protected ribonucleoside phosphoramidite monomers, which are required synthesis two chimeric (20-mers) containing four canonical ribonucleosides. Upon treatment a solution sodium hydroxide, ester-protecting saponified their salts, after ion exchange underwent quantitative intramolecular decarboxylation under neutral conditions at 65 °C provide deprotected marginally better yields those obtained commercial 2'-O-tert-butyldimethylsilyl phosphoramidites highly similar conditions.