DIASTEREOMERS OF NUCLEOSIDE 3'-O-(2-THIO-1,3,2-OXATHIA(SELENA)PHOSPHOLANES) - BUILDING-BLOCKS FOR STEREOCONTROLLED SYNTHESIS OF OLIGO(NUCLEOSIDE PHOSPHOROTHIOATE)S

Diastereomerically pure 5'-O-DMT-nucleoside 3'-O-(2-thio-1,3,2-oxathia phospholanes) (3) and their oxathiaphospholane ring-substituted analog ues (20) were used for the synthesis of stereoregular oligo(nucleoside phosphorothioate)s (S-Oligos). The oxathiaphospholane ring-opening co ndensation requires the presence of strong organic base, preferably DB U. The yield of a single coupling step is ca. 95% and resulting S-Olig os are free of nucleobase- and sugar-phosphorothioate backbone modific ations. The diastereomeric purity of products was estimated on the bas is of diastereoselective degradation with Nuclease P1 and a mixture of snake venom phosphodiesterase and Serratia marcescens endonuclease. T hermal dissociation studies of heteroduplexes S-Oligos/DNA and S-Oligo s/RNA showed that their stability is stereochemistry- and sequence-dep endent.