Large-scale synthesis of oligonucleotide phosphorothioates using 3-amino-1,2,4-dithiazole-5-thione as an efficient sulfur-transfer reagent

A commercially available and inexpensive compound, 3-amino-1,2,4-dithiazole -5-thione (ADTT), is discovered to be a new sulfur-transfer reagent for sol id-phase synthesis of oligonucleotide phosphorothioates via the phosphorami dite method. The efficiency of ADTT was investigated by solid-phase synthes es of dinucleotide and oligonucleotide phosphorothioates. The results show that ADTT is a highly efficient sulfur-transfer reagent and fully compatibl e with automated solid-phase synthesis. ADTT has been applied in manufactur e of oligonucleotide phosphorothioates to reduce the cost significantly.