Ionis Pharmaceuticals, Inc.
Method for solution phase detritylation of oligomeric compounds

Abstract:

Provided herein are methods for the synthesis of oligomeric compounds wherein removal of the 5'-terminal trityl group is performed at reduced temperature and lower pH relative to standard methods. In certain embodiments, the present methods provide detritylated oligomeric compounds having a reduced percentage of depurination relative to the same detritylated oligomeric compounds prepared using standard methods. In certain embodiments, the present methods provide detritylated oligomeric compounds with increased purity relative to the same detritylated oligomeric compounds prepared using standard methods. In certain embodiments, the present methods provide an increased rate of detritylation compared to standard methods.