Among the various classes of modified nucleotides and oligonucleotides, phosphorothioate analogs, in which the sugar-phosphate backbone is modified by the substitution of a sulfur atom for one of the nonbridging oxygen atoms, have been most extensively studied in both in vitro and in vivo experiments. However, this substitution induces P-chirality of the dinucleoside phosphorothioate moiety. Consequently, even short phosphorothioate oligonucleotides synthesized using standard chemical methods exist as mixtures of many diastereoisomers. In our laboratory, the oxathiaphospholane (OTP) method has been developed for a stereocontrolled synthesis of oligo(deoxyribonucleoside phosphorothioate)s. Recently, this approach has been extended to ribonucleoside derivatives, and stereodefined phosphorothioate diribonucleotides were incorporated into oligomers suitable for mechanistic studies on deoxyribozymes. Next, it was found that the OTP ring can be opened with nucleophiles as weak as the phosphate or pyrophosphate anion, giving rise to nucleoside α-thiopolyphosphates. Surprisingly, the reaction between nucleoside OTP and O,O-dialkyl H-phosphonate or O,O-dialkyl H-phosphonothioate led to nucleoside 5'-O-(α-thio-β-O,O-dialkyl-hypophosphate) or 5'-O-(α,β-dithio-β-O,O-dialkyl-hypophosphate), respectively, i.e., derivatives containing a direct P-P bond.