2 APPROACHES TO THE LARGE-SCALE SYNTHESIS OF OLIGONUCLEOTIDE DITHIOATES

The large scale synthesis of oligothymidine dithioates have been carri ed out. Using the triester liquid-phase approach, high purity fully pr otected dimer - tetramer dithioate blocks (in mmolar amounts) and octa mer dithioate (in 0.1 mmol amount) have been obtained. Large scale sol id-phase synthesis, using thioamidite approach and polyethyleneglycol monomethyl ether as support, have been carried out to give 0.02 and 0. 12 mmolar amounts of octamer dithioates T8(S2) and C7T(S2). A new meth od of purification for the oligonucleotide dithioates, synthesised by the solid phase approach, has been introduced; it includes the cleavag e of the protected oligonucleotide from the polymer support, adsorbtio n chromatography on silica gel, total deprotection and low-pressure re verse-phase chromatography on silica gel C18.