Solid phase synthesis of oligoribonucleotides by the phosphoramidite approach using 2′-O-1-(2-chloroethoxy)ethyl protection

Abstract

The new type protecting group, 1-(2-chloroethoxy)ethyl (Cee) group has been employed for the protection of the 2′-OH groups of ribonucleoside residues in the synthesis of oligoribonucleotides by the phosphoramidite approach en a solid support, using the acid-labile 5′-O-dimethaxytrityl (DMTr) group. This group is completely stable under the acidic conditions required to remove the 5t́-terminal protecting groups in oligonucleotide synthesis on a solid support, and yet is easily removable under mild condition of acidic hydrolysis (pH 2.0) for the final unblocking step. The Cee-protected ribonucleoside 3′-phosphoramidite units were evaluated in the synthesis of a series of oligoribonucleotides consisting of the homopolymers of cytidine, the box 9R and 9R' sequences of Tetrahymena rRNA, and a leader sequence of phage Qβ-A protein mRNA. A full data for the deprotection and purification of synthetic oligoribonucleotides are also described.