Stereocontrolled phosphorothioate synthesis using chiral phosphite triesters.

We describe stereocontrolled synthesis of phosphorothioate oligonucleotides including stereospecific transesterification to form chiral phosphite triester backbone under basic conditions. Substrate phosphite triesters with phenoxy derivative substituents as leaving groups were separated into individual stereoisomers and reacted with hydroxyl-containing compounds to form chiral phosphite triester backbone. Subsequent stereoretentive sulfurization and deprotection gave desired stereocontrolled phosphorothioate linkages.