Protection of the 2′‐Hydroxy Function of Ribonucleosides as an Iminooxymethyl Propanoate and Its 2′‐ OO ‐Deprotection through an Intramolecular Decarboxylative Elimination Process

摘要

> The design and implementation of 2′‐hydroxy protecting groups for ribonucleosides is still a daunting challenge to overcome when assembling RNA (ribonucleic acid) sequences for therapeutic applications. The reaction of 2′‐ O ‐aminooxymethylribonucleosides with ethyl pyruvate results in the formation of 2′‐ O ‐iminooxymethyl ethyl propanoates. The cleavage of this type of 2′‐ O ‐protecting groups is demonstrated through saponification of the esters to 2′‐ O ‐iminooxymethyl propanoate salts, which, when needed, decarboxylate quantitatively at 55 °C in the presence of tetra‐ n ‐butylammonium fluoride or chloride in dimethyl sulfoxide (DMSO) to produce all four native ribonucleosides.