METHOD OF RATE ENHANCEMENT FOR TRIESTER SYNTHESIS OF OLIGONUCLEOTIDES USING A CATALYTIC ALCOHOL, AND COMPOUNDS FOR USE THEREIN

摘要

The rate of the triester method of oligonucleotide synthesis is increased by using a phosphotriester formation catalyst/blocking group diester linked to the 3 min phosphate of a nucleotide (or an oligonucleotide), thus forming a nucleotide phosphodiester: Insert here wherein Base is a nucleotide base; wherein Pr is a nucleotide 5 min hydroxyl protecting group, for example, monomethoxytrityl or dimethoxytrityl; wherein R includes a substituted or unsubstituted, aryl, alkyl, cycloalkyl or beta cyanoalkyl blocking group; wherein CAT is a catalytic moiety, which is, for example, a substituted or unsubstituted, nitrogen heterocycle, tertiary amine or a carboxylic acid. The use of these groups so linked to form nucleotide phosphodiesters enhances the rate of an internucleotide condensation reaction. Following condensation (which results in the formation of a phosphotriester) the phosphotriester formation catalyst/blocking group can be removed leaving a di-nucleotide, or the condensation reaction can be repeated to synthesize an oligonucleotide.