Synthesis of Chimeric Oligonucleotides Having Modified Internucleotide Linkages via an Automated H-Phosphonate/Phosphoramidite Approach

This article describes an automated solid-phase approach for the synthesis of chimeric oligonucleotides containing phosphoramidate-modified internucleotide linkages. An optimized H-phosphonate synthetic cycle is combined with the commonly used phosphoramidite approach to obtain oligonucleotides comprising blocks having various types of internucleotide linkages. This article is specific to the synthesis of oligonucleotides having phosphoramidate modifications, but is adaptable to permit the incorporation of other modified linkages accessible through H-phosphonate diester intermediates. © 2018 by John Wiley & Sons, Inc.