The P‐Stereocontrolled Synthesis of PO/PS‐Chimeric Oligonucleotides by Incorporation of Dinucleoside Phosphorothioates Bearing an <i>O</i>‐4‐Nitrophenyl Phosphorothioate Protecting Group

Abstract

Abstract The synthesis of protected model dinucleoside (3',5')‐ O ‐aryl phosphorothioates, their separation into pure diastereomers, and their successful incorporation into oligonucleotides followed by stereospecific deprotection of the O ‐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 O ‐aryl phosphorothioate in “dimeric building blocks” has been assigned. The 3'‐terminal S P ‐phosphorothioate linkages effectively protect such chimeric constructs from degradation by human plasma exonuclease (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2005)