Chimeric oligonucleotides containing phosphodiester and phosphorothioate linkages have been obtained using the solid phase synthesis. The oligonucleotide parts possessing natural internucleotide phosphate bonds were assembled using commercially available nucleoside 3'-O-(2-cyanoethyl-N,N-diisopropylamino)phosphoramidites 7 whereas the phosphorothioate segment was built using nucleoside 3'-O-(2-thio-1,3,2-oxathiaphospholanes) 3. The oxidation steps, crucial for the conversion of phosphite linkages into the phosphate moieties, were conducted using tert-butylperoxy-trimethylsilane, and this reagent was not harmful to the diester phosphorothioate linkages. When P-diastereopure nucleoside 3'-O-(2-thio-1,3,2-oxathiaphospholane) monomers were employed the resulting chimeric backbone retained the P-stereoregularity of the phosphorothioate units.
