NUCLEOSIDE H-PHOSPHONATES .13. STUDIES ON 3H-1,2-BENZODITHIOL-3-ONE DERIVATIVES AS SULFURIZING REAGENTS FOR H-PHOSPHONATE AND H-PHOSPHONOTHIOATE DIESTERS

Formation of O-oxidized products during sulfurization of H-phosphonothioate and H-phosphonate diesters with 3H-1,2-benzodithiol-3-one 1,1-dioxide (1) was found to be due to generation of the O-oxidizing agents, most likely 3H-2,1-benzoxathiol-3-one 1-oxide (4) and 3H-2,1-benzoxathiol-3-one (5), during the course of the reactions. Another source of the side products formation may be the disproportionation of 1 that occurs in the presence of triethylamine. To overcome these problems, a new sulfur-transferring reagent, 3H-1,2-benzodithiol-3-one (3), has been developed. Under aqueous reaction conditions, which are compatible with both solution- and solid-phase synthesis of oligonucleotides, the reagent 3 furnished clean and fast conversion of H-phosphonothioate and H-phosphonate diesters into the corresponding phosphorodi- and phosphoromonothioates.