Synthesis of Oligo(deoxyribonucleoside phosphorodithioate)s by the Dithiaphospholane Approach

Article abstract of DOI:10.1021/jo00126a060

A novel method of synthesis of oligo(deoxyribonucleoside phosphorodithioate)s (S2-ODNs), based on the ring-opening condensation of nucleoside 3'-O-(2-thiono-1,3,2-dithiaphospholane)s with 5'-O-deprotected nucleosi(ti)des in the presence of a strong organic base such as DBU, is presented.The process has been adapted to the requirements of automated solid-phase oligonucleotide synthesis with a relatively short condensation step (5 min) and reasonable step-yield (>95percent).N-Methylpyrrolidin-2-ylidenyl (Pya) was found to be the group of choice for the protection of reactive aminofunctions of nucleobases in nucleotide substrates.Sarcosine-containing linker (LCA CPG SAR) was employed due to its known resistance to cleavage by DBU.Several medium-size S2-ODNs were prepared by this approach.Their identity and purity was confirmed by means of 31P NMR, gel electrophoresis, and mass spectrometry.It has been demonstrated that, contrary to a recent report, S2-ODNs are not degraded by DNaseI.