Ionis Pharmaceuticals, Inc.
SYNTHESIS OF OLIGOMERIC COMPOUNDS COMPRISING PHOSPHOROTHIOATE DIESTER AND PHOSPHODIESTER LINKAGES

Abstract:

The present disclosure provides methods for synthesizing oligomeric compounds having at least one phosphorothioate diester linkage and at least one phosphate diester internucleoside linkage. In certain embodiments, the present disclosure provides oxidation reagents that produce low amounts of unwanted phosphate diester impurities in oligomeric compounds having at least one phosphorothioate diester linkage and at least one phosphate diester internucleoside linkage.