The P-Stereocontrolled Synthesis of PO/PS-Chimeric Oligonucleotides by Incorporation of Dinucleoside Phosphorothioates Bearing an OMICRON-4-Nitrophenyl Phosphorothioate Protecting Group

摘要

The synthesis of protected model dinucleoside(3',5')-OMICRON-aryl phosphorothioates,their separation into pure diastereomers,and their successful incorporation into oligonucleotides followed by stereospecific deprotection of the OMICRON-aryl phosphorothioate function with oximate ion(inversion)enables the preparation of chimeric PO/PS-oligonucleotides with a predetermined sense of P-chirality at each internucleotide phosphorothioate position.The absolute configuration at the phosphorus of the internucleotide OMICRON-aryl phosphorothioate in"dimeric building blocks"has been assigned.The 3'-terminal Sp-phosphorothioate linkages effectively protect such chimeric constructs from degradation by human plasma exonuclease.