EFFICIENT ACTIVATION OF NUCLEOSIDE PHOSPHORAMIDITES WITH 4,5-DICYANOIMIDAZOLE DURING OLIGONUCLEOTIDE SYNTHESIS

A new activator for the coupling of phosphoramidites to the 5'-hydroxy l group during oligonucleotide synthesis is introduced. The observed t ime to complete coupling is twice as fast with 4,5-dicyanoimidazole (D CI) as the activator, compared with 1H-tetrazole. The effectiveness of DCI is thought to be based on its nucleophilicity. DCI is soluble in acetonitrile up to 1.1 M at room temperature and can be used as the so le coupling activator during routine automated solid phase synthesis o f oligonucleotides. The addition of 0.1 M N-methylimidazole to 0.45 M 1H-tetrazole also results in higher product yields during oligonucleot ide synthesis than observed with 1H-tetrazole alone.