Lewis Acidic Bentonite Clays as Catalysts for 5′ Deprotection of Nucleosides and Dinucleotides

Lewis acidic bentonite catalysts enable rapid (<10 min) and quantitative removal of 5′- O -dimethoxytrityl (DMTr) and 5′- O -(2-methoxypropyl) hydroxyl protecting groups. These catalysts selectively deprotect the 5′-OH of protected nucleosides in the presence of standard therapeutic oligonucleotide modifications. Similarly fast and quantitative deprotection of nucleotide dimers was observed, highlighting this method as an attractive option for simplified liquid phase oligonucleotide synthesis (LPOS).