Diastereomers of Nucleoside 3′-O-(2-Thio-1,3,2-oxathia(selena)phospholanes): Building Blocks for Stereocontrolled Synthesis of Oligo(nucleoside phosphorothioate)s

摘要

Diastereomerically pure 5′-O-DMT-nucleoside 3′-O-(2-thio-1,3,2-oxathiaphospholanes) (3) and their oxathiaphospholane ring-substituted analogues (20) were used for the synthesis of stereoregular oligo(nucleoside phosphorothioate)s (S-Oligos). The oxathiaphospholane ring-opening condensation requires the presence of strong organic base, preferably DBU. The yield of a single coupling step is ca. 95% and resulting S-Oligos are free of nucleobase- and sugar-phosphorothioate backbone modifications. The diastereomeric purity of products was estimated on the basis of diastereoselective degradation with Nuclease P1 and a mixture of snake venom phosphodiesterase and Serratia marcescens endonuclease. Thermal dissociation studies of heteroduplexes S-Oligos/DNA and S-Oligos/RNA showed that their stability is stereochemistry- and sequence-dependent.