A liquid-phase process suitable for large-scale synthesis of phosphorothioate oligonucleotides

A new process for the preparation of large amounts of thioate oligonucleoti des in a quasi-classical solution condition is described. This method takes advantage of the use of poly(ethylene glycol) as a soluble, inert support during the synthesis, The quality and amount of the desired oligonucleotide s are improved by the use of pre-formed dimeric phosphoramidite as synthons , The easy intermediate purification from moderate excess of reagents allow s obtaining very high coupling yields, and, consequently, the efficient pro duction of quite long sequences as those required for their pharmacological applications.