SYNTHESIS OF OLIGO(DEOXYRIBONUCLEOSIDE PHOSPHORODITHIOATE)S BY THE DITHIAPHOSPHOLANE APPROACH

A novel method of synthesis of oligo(deoxyribonucleoside phosphorodith ioate)s (S-2-ODNs), based on the ring-opening condensation of nucleosi de 3'-0-(2-thiono-1,3,2-dithiaphospholane)s with 5'-O-deprotected nucl eosi(ti)des in the presence of a strong organic base such as DBU, is p resented. The process has been adapted to the requirements of automate d solid-phase oligonucleotide synthesis with a relatively short conden sation step (5 min) and reasonable step-yield(>95%). N-Methylpyrrolidi n-2-ylidenyl (Pya) was found to be the group of choice for the protect ion of reactive aminofunctions of nucleobases in nucleotide substrates . Sarcosine-containing linker (LCA CPG SAR) was employed due to its kn own resistance to cleavage by DBU. Several medium-size S-2-ODNs were p repared by this approach. Their identity and purity was confirmed by m eans of P-31 NMR, gel electrophoresis, and mass spectrometry. It has b een demonstrated that, contrary to a recent report, S-2-ODNs are not d egraded by DNaseI.