DEOXYRIBONUCLEOSIDE PIRO-4,4-PENTAMETHYLENE-1,3,2-OXATHIAPHOSPHOLANE)S AND PIRO-4,4-PENTAMETHYLENE-1,3,2-OXATHIAPHOSPHOLANE)S - MONOMERS FOR STEREOCONTROLLED SYNTHESIS OF OLIGO(DEOXYRIBONUCLEOSIDE PHOSPHOROTHIOATE)S AND CHIMERIC PS PO OLIGONUCLEOTIDES/

New monomers, 5'-O-DMT-deoxyribonucleoside o''-4,4-pentamethylene-1,3, 2-oxathiaphospholane)s, were prepared and used for the stereocontrolle d synthesis of PS-Oligos via the oxathiaphospholane approach. These mo nomers and their Zero analogues were used for the synthesis of ''chime ric'' constructs (PS/PO-Oligos) possessing phosphate and P-stereodefin ed phosphorothioate internucleotide linkages. The yield of a single co upling step is approximately 92-95%, and resulting oligomers are free of nucleobase- and sugar-phosphorothioate backbone modifications. Ther mal dissociation studies showed that for heteroduplexes formed by [R-P ]-, [S-P]-, or [mix]-PS/PO-T-10 with dA(12), dA(30), Or poly(dA), for each template, the melting temperatures, as well as free Gibbs' energi es of dissociation process, are virtually equal. Stereochemical eviden ce derived from crystallographic analysis of one of the oxathiaphospho lane monomers strongly supports the participation of pentacoordinate i ntermediates in the mechanism of the oxathiaphospholane ring-opening c ondensation.