BASE-CATALYZED TRANSESTERIFICATION METHOD FOR INTERNUCLEOTIDE LINKAGEFORMATION

A new method for oligonucleotide synthesis via organic base catalyzed transesterification, using readily available stable monomer derivative s of tetracoordinated phosphorus was developed. The method can be pote ntially adapted to large-scale synthesis of short oligonucleotide anal ogues in solution and is best suited for the synthesis of methylphosph onate oligonucleotide analogues. The strong organic bases such as 1,8- diazabicyclo[5.4.0]undec-7-ene (DBU) promote the coupling reaction, se rving as base activators of the hydroxyl function of nucleoside compon ent or as nucleophilic agents activating the nucleotide monomer.