Scale-Up of Oligonucleotide Synthesis: Solution Phase

Solution-phase methods have been used for the first synthesis of an internucleotidic bond (1 ) and, some 20 years ago, had a glorious period during the first gene synthesis. At that time, their present-day competitor, the polymer support technique, was also developed and saw some first applications to oligonucleotide preparations (2 ), but it took nearly 15 further years until the solid-phase methods became a serious rival to solution methods. The efficiency of the phosphoramidite chemistry, combined with the development of mechanization, brought about a dramatic change ca. 10 years ago, putting polymer-support synthesis into first place. Yet, solution methods were never completely replaced, and the following survey will testify to their vitality.