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 solid-phase synthesis of oligonucleotide phosphorothioates via the phosphoramidite method. The efficiency of ADTT was investigated by solid-phase syntheses of dinucleotide and oligonucleotide phosphorothioates. The results show that ADTT is a highly efficient sulfur-transfer reagent and fully compatible with automated solid-phase synthesis. ADTT has been applied in manufacture of oligonucleotide phosphorothioates to reduce the cost significantly.