METHOD FOR SOLUTION PHASE DETRITYLATION OF OLIGOMERIC COMPOUNDS

摘要

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 method provide an increased rate of detritylation compared to standard methods.

主权项

1. A method of detritylating 5′-trityl protected oligomeric compounds:
providing an aqueous solution of 5′-trityl protected oligomeric compounds; cooling the aqueous solution to from about 5° C. to about 15° C.; adjusting the pH of the cooled aqueous solution to from about 2.0 to about 3.5 by addition of an acid with mixing; mixing the acidified solution while maintaining the pH from about 2.0 to about 3.5 and maintaining the temperature to from about 5° C. to about 15° C. until essentially all of the 5′-trityl groups are removed; and adjusting the pH of the acidified solution to from about 5.0 to about 7.0 by addition of aqueous sodium hydroxide that is from about 1N to about 10N while maintaining the temperature below about 35° C. to provide the detritylated oligomeric compounds.