DOI: 10.1002/ejoc.202300614 ISSN: 1434-193X

5'‐O‐(2‐Isopropoxyprop‐2‐yl)‐protected Phosphoramidite Building Blocks in the Liquid Phase Oligonucleotide Synthesis

Zehong Liang, Petja Rosenqvist, Ella Pajuniemi, Mikko Ora, Petri Heinonen, Pasi Virta, Mikko Oivanen
  • Organic Chemistry
  • Physical and Theoretical Chemistry


5'‐O‐(2‐isopropoxyprop‐2‐yl) (IIP)‐protection was introduced to 5’‐OH function of nucleosides in high yields by an acid‐catalysed transacetalization with 2,2‐diisopropoxypropane. The applicability of this temporal 5’‐O‐protecting group was demonstrated in the liquid phase oligonucleotide synthesis (LPOS) using the corresponding phosphoramidite building blocks (dA, dG, dC and dT) and a tetrapodal precipitative soluble support. Standard protecting groups were used on nucleobases. Tetrazole as an activator, followed by oxidation using m‐chloroperbenzoic acid, was used for the coupling. The IIP was shown to be a capable choice to the 5’‐O protection in solution phase synthesis. It could be readily removed with formic acid (t1/2<10 s in 6 % HCOOH in dichloromethane/methanol (2/1) at RT), resulting in volatile byproducts (acetone and isopropanol).

More from our Archive