Polysulfide reagent in solid-phase synthesis of phosphorothioate oligonucleotides: greater than 99.8% sulfurization efficiency.

A solution of sulfur (0.1 M) and sodium sulfide (0.01 M) in 3-picoline, referred to as polysulfide reagent, rapidly converts trialkyl and triaryl phosphite triesters to the corresponding phosphorothioate derivatives. Greater than 99.8% average stepwise sulfurization efficiency is obtained in the solid phase synthesis of DNA and RNA phosphorothioate oligonucleatides via the phosphoramidite approach.