Oligoribonucleotide synthesis by the use of 1-(2-cyanoethoxy)ethyl (CEE) as a 2′-hydroxy protecting group

A novel method for the synthesis of oligoribonucleotides using 1-(2-cyanoethoxy)ethyl (CEE) as a 2′-hydroxy protecting group has been developed. A CEE group was introduced to the 2′-position of N-acyl-3′,5′-O-silyl-protected ribonucleosides under acidic conditions in good yields. The 2′-O-CEE group was found to be stable in an aqueous or ethanolic ammonia and was quickly removed by treatment with anhydrous tetrabutylammonium fluoride (TBAF). A combination of the use of N-acyl and 2′-O-CEE protecting groups enabled a reliable and complete two-step deprotection, first with NH3–EtOH, then with TBAF in THF, without cleavage of internucleotidic linkages.