Synthesis of 5'-C- and 2'-O-(bromoalkyl)-substituted ribonucleoside phosphoramidites for the post-synthetic functionalization of oligonucleotides on solid support

Abstract

The preparation of building blocks for the incorporation of 6′-O-(5-bromopentyl)-substituted β-D-allofuranosylnucleosides and 2′-O-[(3-bromopropoxy)methyl]-substituted ribonucleosides into oligonucleotide sequences is presented (Schemes 1 and 2). These reactive building blocks can be modified with a variety of soft nucleophiles while the (fully protected) sequence is still attached to the solid support. As an example of this strategy, we carried out some preliminary solid-phase substitution and conjugation reactions with DNA sequences containing a 2′-O-[(3-bromopropoxy)methyl]-substituted ribonucleoside (Scheme 3) and determined the pairing properties of duplexes obtained therefrom.