SYNTHESIS OF DIRIBONUCLEOSIDE PHOSPHOROTHIOATES VIA STEREOSPECIFIC SULFURIZATION OF H-PHOSPHONATE DIESTERS

Sulfurization of diribonucleoside H-phosphonates with elemental sulfur was found to be a stereospecific reaction. With this finding as the basis, an efficient method for the preparation of stereochemically homogeneous diribonucleoside phosphorothioates has been developed. The procedure consists of the synthesis and separation of the diastereomeric (R(p) and S(p)) pairs of the corresponding H-phosphonate diesters, followed by their stereospecific sulfurization and a single deprotection step using fluoride ion. The methodology has been used in synthesis of eight diribonucleoside phosphorothioates (four pairs of R(p) and S(p) diastereomers).