5'-O-(2-Isopropoxyprop-2-yl)-protected Phosphoramidite Building Blocks in the Liquid Phase Oligonucleotide Synthesis
: Liang Zehong, Rosenqvist Petja, Pajuniemi Ella, Ora Mikko, Heinonen Petri, Virta Pasi, Oivanen Mikko
Publisher: WILEY-V C H VERLAG GMBH
: 2023
: European Journal of Organic Chemistry
: EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
: EUR J ORG CHEM
: e202300614
: 6
: 1434-193X
: 1099-0690
DOI: https://doi.org/10.1002/ejoc.202300614(external)
: https://doi.org/10.1002/ejoc.202300614(external)
: https://research.utu.fi/converis/portal/detail/Publication/180811837(external)
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).