An Unconventional Acid-Labile Nucleobase Protection Concept for Guanosine Phosphoramidites in RNA Solid-Phase Synthesis

摘要

We present an innovative O⁶-tert-butyl/N²-tert-butyloxycarbonyl protection concept for guanosine (G) phosphoramidites. This concept is advantageous for 2′-modified G building blocks because of very efficient synthetic access when compared with existing routes that usually employ O⁶-(4-nitrophenyl)ethyl/N²-acyl protection or that start from 2-aminoadenosine involving enzymatic transformation into guanosine later on in the synthetic path. The new phosphoramidites are fully compatible with 2′-O-tBDMS or TOM phosphoramidites in standard RNA solid-phase synthesis and deprotection, and provide excellent quality of tailored RNAs for the growing range of applications in RNA biophysics, biochemistry, and biology.