API Support

5'-O-(2-Isopropoxyprop-2-yl)-protected Phosphoramidite Building Blocks (IIP-protected) represent an innovative approach in the liquid phase oligonucleotide synthesis (LPOS) for protecting the 5'-OH functionality of nucleosides. This protection method was achieved through an acid-catalyzed transacetalization with 2,2-diisopropoxypropane, providing high yields and efficient 5'-O protection. The IIP protection was applied to the phosphoramidite building blocks of nucleosides (dA, dG, dC, and dT) using a tetrapodal precipitative soluble support.
The utility of IIP protection in LPOS was demonstrated by employing standard nucleobase protecting groups, tetrazole as the activator, and m-chloroperbenzoic acid for oxidation, facilitating efficient coupling. The IIP group exhibited several advantages, such as fast cleavage with formic acid (half-life<10 s in 6% HCOOH in dichloromethane/methanol at room temperature), resulting in the formation of volatile byproducts—acetone and isopropanol. These byproducts enhance atom economy and minimize residual waste, making the IIP-protected phosphoramidite building blocks a sustainable option for oligonucleotide synthesis.
The IIP protection group's small size and its ability to be removed quickly without leaving significant non-volatile residues further contribute to the efficiency and practicality of the method. This protection strategy can be integrated into current phosphoramidite chemistry workflows, offering a highly effective means of synthesizing short 2'-deoxyoligonucleotides while maintaining high yield and purity.